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1.
Science ; 371(6534)2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33707240

RESUMO

Infections with many Gram-negative pathogens, including Escherichia coli, Salmonella, Shigella, and Yersinia, rely on type III secretion system (T3SS) effectors. We hypothesized that while hijacking processes within mammalian cells, the effectors operate as a robust network that can tolerate substantial contractions. This was tested in vivo using the mouse pathogen Citrobacter rodentium (encoding 31 effectors). Sequential gene deletions showed that effector essentiality for infection was context dependent and that the network could tolerate 60% contraction while maintaining pathogenicity. Despite inducing very different colonic cytokine profiles (e.g., interleukin-22, interleukin-17, interferon-γ, or granulocyte-macrophage colony-stimulating factor), different networks induced protective immunity. Using data from >100 distinct mutant combinations, we built and trained a machine learning model able to predict colonization outcomes, which were confirmed experimentally. Furthermore, reproducing the human-restricted enteropathogenic E. coli effector repertoire in C. rodentium was not sufficient for efficient colonization, which implicates effector networks in host adaptation. These results unveil the extreme robustness of both T3SS effector networks and host responses.


Assuntos
Proteínas de Bactérias/metabolismo , Citrobacter rodentium/patogenicidade , Infecções por Enterobacteriaceae/microbiologia , Redes e Vias Metabólicas , Sistemas de Secreção Tipo III/metabolismo , Animais , Proteínas de Bactérias/genética , Citrobacter rodentium/genética , Infecções por Enterobacteriaceae/imunologia , Feminino , Deleção de Genes , Imunidade , Camundongos , Camundongos Endogâmicos C57BL , Proteólise , Sistemas de Secreção Tipo III/genética , Virulência
2.
Methods Mol Biol ; 2291: 399-418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704766

RESUMO

Citrobacter rodentium is a natural enteric mouse pathogen that models human intestinal diseases, such as pathogenic E. coli infections, ulcerative colitis, and colon cancer. Upon reaching the monolayer of intestinal epithelial cells (IECs) lining the gut, a complex web of interactions between the host, the pathogen, and the microbiota ensues. A number of studies revealed surprisingly rapid changes in IEC bioenergetics upon infection, involving a switch from oxidative phosphorylation to aerobic glycolysis, leading to mucosal oxygenation and subsequent changes in microbiota composition. Microbiome studies have revealed a bloom in Enterobacteriaceae during C. rodentium infection in both resistant (i.e., C57BL/6) and susceptible (i.e., C3H/HeN) strains of mice concomitant with a depletion of butyrate-producing Clostridia. The emerging understanding that dysbiosis of cholesterol metabolism is induced by enteric infection further confirms the pivotal role immunometabolism plays in disease outcome. Inversely, the host and microbiota also impact upon the progression of infection, from the susceptibility of the distal colon to C. rodentium colonization to clearance of the pathogen, both via opsonization from the host adaptive immune system and out competition by the resident microbiota. Further complicating this compendium of interactions, C. rodentium exploits microbiota metabolites to fine-tune virulence gene expression and promote colonization. This chapter summarizes the current knowledge of the myriad of pathogen-host-microbiota interactions that occur during the progression of C. rodentium infection in mice and the broader implications of these findings on our understanding of enteric disease.


Assuntos
Citrobacter rodentium/fisiologia , Infecções por Enterobacteriaceae , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Animais , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/patologia , Humanos , Camundongos
3.
BMC Infect Dis ; 21(1): 235, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33639886

RESUMO

BACKGROUND: This study aimed to determine the epidemiological, microbiological, and molecular characteristics of an outbreak of carbapenem-resistant Leclercia adecarboxylata in three hospitals associated with the unintended use of contaminated total parental nutrition (TPN). METHODS: For 10 days, 25 patients who received intravenous TPN from the same batch of a formula developed sepsis and had blood cultures positive for L. adecarboxylata. Antimicrobial susceptibility and carbapenemase production were performed in 31 isolates, including one from an unopened bottle of TPN. Carbapenemase-encoding genes, extended-spectrum ß-lactamase-encoding genes were screened by PCR, and plasmid profiles were determined. Horizontal transfer of carbapenem resistance was performed by solid mating. Clonal diversity was performed by pulsed-field gel electrophoresis. The resistome was explored by whole-genome sequencing on two selected strains, and comparative genomics was performed using Roary. RESULTS: All 31 isolates were resistant to aztreonam, cephalosporins, carbapenems, trimethoprim/sulfamethoxazole, and susceptible to gentamicin, tetracycline, and colistin. Lower susceptibility to levofloxacin (51.6%) and ciprofloxacin (22.6%) was observed. All the isolates were carbapenemase producers and positive for blaNDM-1, blaTEM-1B, and blaSHV-12 genes. One main lineage was detected (clone A, 83.9%; A1, 12.9%; A2, 3.2%). The blaNDM-1 gene is embedded in a Tn125-like element. Genome analysis showed genes encoding resistance for aminoglycosides, quinolones, trimethoprim, colistin, phenicols, and sulphonamides and the presence of IncFII (Yp), IncHI2, and IncHI2A incompatibility groups. Comparative genomics showed a major phylogenetic relationship among L. adecarboxylata I1 and USDA-ARS-USMARC-60222 genomes, followed by our two selected strains. CONCLUSION: We present epidemiological, microbiological, and molecular evidence of an outbreak of carbapenem-resistant L. adecarboxylata in three hospitals in western Mexico associated with the use of contaminated TPN.


Assuntos
Surtos de Doenças , Infecções por Enterobacteriaceae/etiologia , Enterobacteriaceae/metabolismo , Nutrição Parenteral Total/efeitos adversos , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Bacteriemia/epidemiologia , Bacteriemia/etiologia , Bacteriemia/microbiologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Criança , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Genoma Bacteriano/genética , Hospitais , Humanos , México/epidemiologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Filogenia , beta-Lactamases/genética
4.
BMC Infect Dis ; 21(1): 85, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468073

RESUMO

BACKGROUND: To determine the phenotype, molecular characterisation and risk factors of postoperative meningitis induced by Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in China. METHODS: We performed a multi-centre comparative cohort study of postoperative meningitis patients infected with Enterobacteriaceae in 4 neurosurgical centres in China from January 2014 to December 2019. Phenotype and molecular characteristics of the isolates were reviewed and tested, and independent risk factors of the EPE meningitis were evaluated by binary logistic regression. RESULTS: In total, 220 Enterobacteriaceae include 78 EPE were available in this study. 85.6% (67/78) ESBL-related genes were tested, and blaSHV (14.9%) and blaSHV + blaTEM + blaCTX-M-9 (20.9%) were found to be the most frequent mono and combined ESBL-related genes harboured by Enterobacteriaceae. On binary logistic analysis, craniotomy (OR. 2.583, 95% C.I. 1.274-5.235, P = 0.008) and malignancy (OR. 2.406, 95% C.I. 1.299-4.456, P = 0.005) were the associated independent risk factors to meningitis induced by EPE. CONCLUSIONS: To the best of our knowledge, this is the largest series focusing on risk factors of EPE meningitis which has been conducted in China. Craniotomy and malignancy were independent risk factors for EPE meningitis. The risk factors identified may be further utilized in clinical practice and research to avoid and reduce the mortality in future.


Assuntos
Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/isolamento & purificação , Meningites Bacterianas/epidemiologia , beta-Lactamases/metabolismo , Adulto , China/epidemiologia , Estudos de Coortes , Enterobacteriaceae/genética , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/líquido cefalorraquidiano , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/microbiologia , Fenótipo , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/líquido cefalorraquidiano , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos , Fatores de Risco
5.
BMC Infect Dis ; 21(1): 13, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407223

RESUMO

BACKGROUND: Enterobacter cloacae (E. cloacae) is one of the commensal flora in the human intestinal tract and a prevalent nosocomial pathogen, which rarely causes infectious osteoarthritis in immunocompetent patients without recent trauma or surgery. Here, we report the first case of septic monoarthritis of the shoulder caused by E. cloacae in an immunocompetent patient. CASE PRESENTATION: A 52-year-old female with a 6-year history of right shoulder pain was referred to our emergency department due to fever, acute severe shoulder pain, and swelling. Blood test showed elevated inflammatory markers. The patient denied any recent invasive surgical procedure and trauma. She was misdiagnosed with a frozen shoulder, and the anti-inflammatory painkiller celecoxib for symptomatic treatment was ineffective. Magnetic resonance imaging (MRI) showed a shoulder joint abscess and supraspinatus tendon tear. The joint aspirate culture showed E. cloacae. After late diagnosis, she was treated with levofloxacin and underwent surgical debridement and irrigation. Her follow-up data revealed that she did not suffer from shoulder swelling and severe pain. CONCLUSION: This is a rare case of E. cloacae infected arthritis of the shoulder in an immunocompetent patient with a rotator cuff tear, indicating that even if the symptoms and age of the patients match the characteristics of frozen shoulder, the possibility of septic arthritis should be considered in the presence of fever and increasing inflammatory markers. The cases of our literature review suggest that the patients subjected to invasive procedure may develop a subsequent E. cloacae osteoarticular infection, regardless of being asymptomatic after the procedure.


Assuntos
Artrite Infecciosa/diagnóstico , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Dor de Ombro/diagnóstico , Ombro/microbiologia , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/microbiologia , Artrite Infecciosa/cirurgia , Desbridamento , Diagnóstico Tardio , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/cirurgia , Feminino , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Levofloxacino/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Dor de Ombro/microbiologia , Resultado do Tratamento
6.
PLoS One ; 15(12): e0243630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332370

RESUMO

Enterobacterales resistant to carbapenems, a class of last-resort antimicrobials, are ranked as an "urgent" and "critical" public health hazard by CDC and WHO. IMP-type carbapenemase-containing Enterobacterales are endemic in Japan, and blaIMP-6 is one of the notable carbapenemase genes responsible for the resistance. The gene is plasmid-encoded and confers resistance to meropenem, but not to imipenem. Therefore, IMP-6-producing Enterobacterales isolates are occasionally overlooked in clinical laboratories and are referred to as 'stealth-type'. Since previous reports in Japan were confined only to some geographical regions, their distribution across prefectures and the factors affecting the distribution remain unclear. Here, we revealed the dynamics of the geographical distribution of Enterobacterales with IMP-6 phenotype associated with antimicrobial use in Japan. We utilized comprehensive national surveillance data of all routine bacteriological test results from more than 1,400 hospitals in 2015 and 2016 to enumerate Escherichia coli and Klebsiella pneumoniae isolates with the antimicrobial susceptibility pattern (phenotype) characteristic of IMP-6 (imipenem susceptible, meropenem resistant), and to tabulate the frequency of isolates with the phenotype for each prefecture. Isolates were detected in approximately half of all prefectures, and combined analysis with the national data of antimicrobial usage revealed a statistically significant association between the frequency and usage of not carbapenems but third-generation cephalosporins (p = 0.006, logistic mixed-effect regression) and a weaker association between the frequency and usage of fluoroquinolones (p = 0.043). The usage of third-generation cephalosporins and fluoroquinolones may select the strains with the IMP-6 phenotype, and contribute to their occasional spread. We expect the findings will promote antimicrobial stewardship to reduce the spread of the notable carbapenemase gene.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/genética , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Humanos , Imipenem/farmacologia , Imipenem/uso terapêutico , Japão/epidemiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném/farmacologia , Meropeném/uso terapêutico , Fenótipo
7.
Mar Drugs ; 18(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348729

RESUMO

Edwardsiella tarda can cause fatal gastro-/extraintestinal diseases in fish and humans. Overuse of antibiotics has led to antibiotic resistance and contamination in the environment, which highlights the need to find new antimicrobial agents. In this study, the marine peptide-N6 was amidated at its C-terminus to generate N6NH2. The antibacterial activity of N6 and N6NH2 against E. tarda was evaluated in vitro and in vivo; their stability, toxicity and mode of action were also determined. Minimal inhibitory concentrations (MICs) of N6 and N6NH2 against E. tarda were 1.29-3.2 µM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of E. tarda and binding to lipopolysaccharide (LPS) and genomic DNA. In contrast with N6, N6NH2 improved the stability toward trypsin, reduced hemolysis (by 0.19% at a concentration of 256 µg/mL) and enhanced the ability to penetrate the bacterial outer and inner membrane. In the model of fish peritonitis caused by E. tarda, superior to norfloxacin, N6NH2 improved the survival rate of fish, reduced the bacterial load on the organs, alleviated the organ injury and regulated the immunity of the liver and kidney. These data suggest that the marine peptide N6NH2 may be a candidate for novel antimicrobial agents against E. tarda infections.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Edwardsiella tarda/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/virologia , Doenças dos Peixes/tratamento farmacológico , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Membrana Celular/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/patologia , Proteínas de Peixes , Rim/patologia , Fígado/patologia , Testes de Sensibilidade Microbiana , Norfloxacino/uso terapêutico , Peritonite/tratamento farmacológico , Peritonite/etiologia , Relação Estrutura-Atividade , Análise de Sobrevida
8.
Medicine (Baltimore) ; 99(50): e23410, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327265

RESUMO

Carbapenemase-producing organisms (CPO) have been identified as an urgent healthcare threat. Various methods have been used for the detection of CPO using rectal swabs. Recently, an on-demand polymerase chain reaction (PCR) assay, namely, the Xpert Carba-R assay, that requires less than an hour of turnaround time, had been developed for CPO detection in clinical samples. This study focused on the use of this assay to determine the intestinal colonization rate of CPO in patients admitted to emergency rooms (ERs).A retrospective review of medical records was conducted at a tertiary hospital between July 2017 and June 2018. CPO screening using rectal swabs was performed for patients transferred from other hospitals or for those who tested positive in CPO culture tests in the previous three months. The Xpert Carba-R assay and culture tests were used as the CPO screening methods, and the results of both tests were compared.Medical records of 705 patients admitted to our hospital during the study period were reviewed. Of these, 31 (4.4%) showed positive results for CPO using the Xpert Carba-R assay, and these patients were then transferred from the ERs to isolation rooms. Fifteen of the Xpert Carba-R assay-positive patients were also positive for the culture test; hence, early detection enabled the rapid isolation of CPO-infected patients and prevented the spread of the CPO.The Xpert Carba-R assay is a rapid test to identify and guide infection control programs to contain the spread of the rectal colonization of CPO within a hospital.


Assuntos
Técnicas Bacteriológicas/métodos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Enterococos Resistentes à Vancomicina/isolamento & purificação , Serviço Hospitalar de Emergência , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Isolamento de Pacientes , Prevalência , Reto/microbiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
PLoS One ; 15(10): e0237365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33075076

RESUMO

BACKGROUND: Urinary tract infections caused by extended-spectrum beta-lactamase producing Enterobacterales (ESBL-EB) are a problem increasing in our clinical practice. OBJECTIVES: The aim of this study was to evaluate the clinical outcome in patients who received short (≤ 7 days) versus long courses (>7 days) of antimicrobial therapy for complicated ESBL-EB urinary tract infections. METHODS: This is a retrospective and observational study. Positive urine cultures for ESBL-EB in our hospital between March 2015 and July 2017 were identified. Patients with complicated urinary tract infection were included. Differences between treatment groups (7 days or less vs more than 7 days) were analyzed according to baseline characteristics and severity of clinical presentation. Primary outcome was all cause 30-day mortality. Secondary outcome was a combined item of all cause mortality and reinfection by the same enterobacteria at 30 days. RESULTS: 273 urine cultures were positive for ESBL-EB during the study period. 75 episodes were included, 40 in the long treatment group and 35 in the short treatment group. Mean treatment duration in short and long treatment groups was 6,1 and 13,8 days respectively. Mortality at 30 days was 5,7% in the short treatment group and 5% in the long treatment group without significant differences (P = 0,8). Mortality or reinfection by the same ESBL-EB at 30 days was 8,6% in the short treatment group and 10% in the long treatment group, without significant differences (P = 0,8). CONCLUSIONS: Short courses of antimicrobial treatment seems to be effective as treatment of complicated urinary tract infections by ESBL-EB.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Idoso , Idoso de 80 Anos ou mais , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Duração da Terapia , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Infecções Urinárias/mortalidade , Resistência beta-Lactâmica
10.
PLoS One ; 15(10): e0230037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33104733

RESUMO

BACKGROUND: Bacteremia is a leading cause of mortality in developing countries, however, etiologic evaluation is infrequent and empiric antibiotic use not evidence-based. Here, we evaluated the patterns of ESBL resistance in children enrolled into a surveillance study for community acquired bacteremic syndromes across health facilities in Central and Northwestern Nigeria. METHOD: Blood culture was performed for children aged less than 5 years suspected of having sepsis from Sept 2008-Dec 2016. Blood was incubated using the BACTEC00AE system and Enterobacteriacea identified to the species level using Analytical Profile Index (API20E®). Antibiotic susceptibility profile was determined by the disc diffusion method. Real time PCR was used to characterize genes responsible for ESBL production. RESULT: Of 21,000 children screened from Sept 2008-Dec 2016, 2,625(12.5%) were culture-positive. A total of 413 Enterobacteriaceae available for analysis were screened for ESBL. ESBL production was detected in 160 Enterobacteriaceae, high resistance rates were observed among ESBL-positive isolates for Ceftriaxone (92.3%), Aztreonam (96.8%), Cefpodoxime (96.3%), Cefotaxime (98.8%) and Trimethoprim/sulfamethoxazole (90%), while 87.5%, 90.7%, and 91.9% of the isolates were susceptible to Imipenem, Amikacin and Meropenem respectively. Frequently detected resistance genes were blaTEM-83.8% (134/160), and, blaCTX-M 83.1% (133/160) followed by blaSHVgenes 66.3% (106/160). Co-existence of blaCTX-M, blaTEM and blaSHV was seen in 94/160 (58.8%), blaCTX-M and blaTEM in 118/160 (73.8%), blaTEM and blaSHV in 97/160 (60.6%) and blaCTX-M and blaSHV in 100/160 (62.5%) of isolates tested. CONCLUSION: Our results indicate a high prevalence of bacteremia from ESBL Enterobacteriaceae in this population of children. These are resistant to commonly used antibiotics and careful choice of antibiotic treatment options is critical. Further studies to evaluate transmission dynamics of resistance genes could help in the reduction of ESBL resistance in these settings.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/classificação , Resistência beta-Lactâmica , Bacteriemia/microbiologia , Pré-Escolar , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Medicina Baseada em Evidências , Feminino , Humanos , Lactente , Espécies Introduzidas , Masculino , Nigéria/epidemiologia , Vigilância da População , Prevalência
11.
BMC Infect Dis ; 20(1): 682, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942989

RESUMO

BACKGROUND: Enterobacter cloacae species is responsible for nosocomial outbreaks in vulnerable patients in neonatal intensive care units (NICU). The environment can constitute the reservoir and source of infection in NICUs. Herein we report the impact of preventive measures implemented after an Enterobacter cloacae outbreak inside a NICU. METHODS: This retrospective study was conducted in one level 3 NICU in Lyon, France, over a 6 year-period (2012-2018). After an outbreak of Enterobacter cloacae infections in hospitalized neonates in 2013, several measures were implemented including intensive biocleaning and education of medical staff. Clinical and microbiological characteristics of infected patients and evolution of colonization/infection with Enterobacter spp. in this NICU were retrieved. Moreover, whole genome sequencing was performed on 6 outbreak strains. RESULTS: Enterobacter spp. was isolated in 469 patients and 30 patients developed an infection including 2 meningitis and 12 fatal cases. Preventive measures and education of medical staff were not associated with a significant decrease in patient colonisation but led to a persistent decreased use of cephalosporin in the NICU. Infection strains were genetically diverse, supporting the hypothesis of multiple hygiene defects rather than the diffusion of a single clone. CONCLUSIONS: Grouped cases of infections inside one setting are not necessarily related to a single-clone outbreak and could reveal other environmental and organisational problematics. The fight against implementation and transmission of Enterobacter spp. in NICUs remains a major challenge.


Assuntos
Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/prevenção & controle , Controle de Infecções/métodos , Surtos de Doenças/prevenção & controle , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , França , Humanos , Higiene , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Estudos Retrospectivos , Sequenciamento Completo do Genoma
12.
J Med Microbiol ; 69(10): 1235-1239, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32924918

RESUMO

Introduction. Increased carbapenem resistance is often caused by carbapenemase production.Aim. The objective of our study was to assess which antibiotic susceptibility patterns, as tested by automated systems, are highly associated with the absence of carbapenemase production in Enterobacteriaceae isolates, and could therefore be used as a screening tool.Methodology. Routine antibiotic susceptibility testing data from 42 medical microbiology laboratories in the Netherlands in the period between January 2011 and June 2017 were obtained from the national antimicrobial resistance surveillance programme. Data on Enterobacteriaceae isolates that had an elevated minimum inhibitory concentration (MIC) for carbapenems (meropenem >0.25 mg l-1 or imipenem >1.0 mg l-1) were selected and subjected to phenotypic or genotypic carbapenemase production testing. Routinely available amoxicillin/clavulanic acid, piperacillin/tazobactam, cefuroxime and ceftriaxone/cefotaxime susceptibilities were studied in relation to carbapenemase production by calculating the negative predictive value.Results. No evidence for carbapenemase-producing Enterobacteriaceae (CPE) was found in 767 of 1007 (76 %) isolates. The negative predictive value was highest for amoxicillin/clavulanic acid (99.6 %) and piperacillin/tazobactam (98.8 %).Conclusion. Enterobacteriaceae isolates with elevated carbapenem MICs that are susceptible to amoxicillin/clavulanic acid or piperacillin/tazobactam are unlikely to be carbapenemase producers. Preselection based on this susceptibility pattern may lead to increased laboratory efficiency and reduction of costs. Whether this is also true for countries with a different distribution of CPE species and types or a higher prevalence of CPE needs to be studied.


Assuntos
Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Carbapenêmicos/farmacologia , Enterobacteriaceae/metabolismo , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/microbiologia , Humanos , Imipenem , Testes de Sensibilidade Microbiana , Países Baixos , Combinação Piperacilina e Tazobactam , beta-Lactamas/farmacologia
13.
Nat Commun ; 11(1): 4457, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901017

RESUMO

Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.


Assuntos
Ácidos Graxos Voláteis/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Interleucinas/biossíntese , Animais , Butiratos/imunologia , Butiratos/metabolismo , Butiratos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Citrobacter rodentium , Colite/imunologia , Colite/microbiologia , Colite/prevenção & controle , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/prevenção & controle , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Microbioma Gastrointestinal/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas In Vitro , Interleucinas/deficiência , Interleucinas/genética , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Regiões Promotoras Genéticas , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo
14.
PLoS Comput Biol ; 16(8): e1008106, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797079

RESUMO

Antibiotic resistance is rising and we urgently need to gain a better quantitative understanding of how antibiotics act, which in turn would also speed up the development of new antibiotics. Here, we describe a computational model (COMBAT-COmputational Model of Bacterial Antibiotic Target-binding) that can quantitatively predict antibiotic dose-response relationships. Our goal is dual: We address a fundamental biological question and investigate how drug-target binding shapes antibiotic action. We also create a tool that can predict antibiotic efficacy a priori. COMBAT requires measurable biochemical parameters of drug-target interaction and can be directly fitted to time-kill curves. As a proof-of-concept, we first investigate the utility of COMBAT with antibiotics belonging to the widely used quinolone class. COMBAT can predict antibiotic efficacy in clinical isolates for quinolones from drug affinity (R2>0.9). To further challenge our approach, we also do the reverse: estimate the magnitude of changes in drug-target binding based on antibiotic dose-response curves. We overexpress target molecules to infer changes in antibiotic-target binding from changes in antimicrobial efficacy of ciprofloxacin with 92-94% accuracy. To test the generality of our approach, we use the beta-lactam ampicillin to predict target molecule occupancy at MIC from antimicrobial action with 90% accuracy. Finally, we apply COMBAT to predict antibiotic concentrations that can select for resistance due to novel resistance mutations. Using ciprofloxacin and ampicillin as well defined test cases, our work demonstrates that drug-target binding is a major predictor of bacterial responses to antibiotics. This is surprising because antibiotic action involves many additional effects downstream of drug-target binding. In addition, COMBAT provides a framework to inform optimal antibiotic dose levels that maximize efficacy and minimize the rise of resistant mutants.


Assuntos
Antibacterianos , Biologia Computacional/métodos , Desenvolvimento de Medicamentos/métodos , Quinolonas , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Modelos Biológicos , Quinolonas/administração & dosagem , Quinolonas/química , Quinolonas/metabolismo , Quinolonas/farmacologia
15.
BMC Infect Dis ; 20(1): 557, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736605

RESUMO

BACKGROUND: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. METHODS: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 µg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. RESULTS: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07-69.88, p = 0.01). CONCLUSIONS: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Fezes/microbiologia , beta-Lactamases/biossíntese , Adolescente , Adulto , Antibacterianos/uso terapêutico , Ceftazidima , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta , Tanzânia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
16.
Zhonghua Er Ke Za Zhi ; 58(8): 640-645, 2020 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-32842384

RESUMO

Objective: To explore the clinical features and treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in pediatric liver transplantation recipients and discuss the significance of CRE colonization by screening with rectal swabs. Methods: A total of 286 cases of pediatic liver transplantation recipients, who came from Tianjin First Central Hospital during August 1,2017 to August 1, 2018, were retrospectively investigated. The clinical characteristics, antibiotic susceptibity test, treatment outcomes and prognosis of CRE infection patients were analyzed. CRE colonization were screened by rectal swabs after liver transplantation. All cases were divided into CRE colonization group and non-CRE colonization group based on CRE colonization results. The high risk factors of CRE colonization and its relationship with CRE infection were investigated. χ(2) test was used for the comparison between groups.The single-factor analysis was used to screen risk factors. Results: The 286 cases included 132 male and 154 female cases. The age was (8±4) months.CRE infection rate after liver transplantation was 7.3% (21/286). The time of CRE infection was the 5(th) (1(th)-14(th)) days after transplantation. Abdominal infection was the most common (95.2%, 20/21), followed by bloodstream infection (12 cases) and pulmonary infection (8 cases). Infection in two or more sites accounted for 71.4% (15/21); 27 CRE strains, in which 24 strains were carbapenem-resistant Klebsiella pneumonia (88.9%), 2 strains were carbapenem-resistant Escherichia coli (7.4%) and one strain was carbapenem-resistant Enterobacter aerogenes (3.7%). The drug resistance rate of CRE strains to carbapenems, penicillin antibiotics, second-and third-generation cephalosporin was 100.0%. Medication treatment included meropenem+fosfomycin (13 cases) and meropenem+tegacycline (8 cases). The treatment was effective in 16 cases and the time was 19 (1-27) d. The 1-year survival rate among CRE infection group and non-CRE infection group were 71.4% (15/21) and 98.1% (260/265), respectively (χ(2)=37.460, P<0.01). CRE infection rate among CRE colonization group and non-CRE colonization group were 26.4% (19/72) and 0.9% (2/214), respectively (χ(2)=51.300, P<0.01). Factors before transplantation, including third-generation cephalosporin or carbapenems exposure, prolonged hospital stay within 3 months, CRE infection, and factors after transplantation, including emergency surgery, mechanical ventilation more than 24 hours (χ(2)=20.570, 6.411, 13.960, 14.600, 9.560, all P<0.01) were high risk factors for CRE colonization. Conclusions: The prognosis of CRE infection after pediatric liver transplantation is poor. Timely diagnosis and treatment are of great importance. Much attention should be paid on CRE rectal colonization and its risk factors. Screening of CRE colonization is important for early warning and control of CRE infection.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Transplante de Fígado , Complicações Pós-Operatórias/microbiologia , Criança , China , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Resistência beta-Lactâmica
17.
Mikrobiyol Bul ; 54(2): 191-202, 2020 Apr.
Artigo em Turco | MEDLINE | ID: mdl-32723275

RESUMO

Carbapenems are used in the treatment of infections caused by multidrug-resistant bacteria and colistin (polymyxin E) is used as the last choice of antimicrobial agent in those resistant to carbapenems. The worldwide and increased use of colistin, which causes cell death by disrupting the permeability of the cytoplasmic membrane of gram-negative bacteria, raised the problem of resistance. The transferable colistin resistance enzyme mcr, is a phosphoethanolamine transferase that adds phosphoethanolamine to lipid A and modifies lipopolysaccharides, leading to polymyxin resistance. The aim of this study was to investigate some of the most prevalent plasmid mediated colistin and carbapenemase resistance genes in colistin resistant Enterobacterales isolates. Enterobacterales isolates which were isolated in the samples of patients treated in the clinical units between October 2016 and September 2018 in the Karadeniz Technical University Faculty of Medicine Farabi Hospital Medical Microbiology Laboratory were included in the study. In addition to conventional methods, isolates were identified to the species level by MALDI-TOF MS (Bruker Daltonics, Germany). The antibiotic susceptibilities of Enterobacterales isolates were studied by an automated microbiology system (Phoenix, Becton Dickinson, USA) and evaluated according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. In isolates that are resistant to colistin, and the isolates that are found to be sensitive but should be included in the patient report of the colistin susceptibility test, colistin susceptibility tests were repeated with liquid microdilution method in accordance with EUCAST standards. The presence of extended spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase were determined by phenotypic methods according to EUCAST recommendations in colistin resistant Enterobacterales isolates. Furthermore, resistance genes of mcr-1-5, blaOXA-48, blaKPC, blaNDM, blaVIM, blaIMP were detected by polymerase chain reaction (PCR) method, followed by nucleotide sequence analysis of the amplified products. In our study, 14657 Enterobacterales isolates belonging to 7535 patients treated in different clinical units were examined retrospectively. Escherichia coli 61.2% (n= 8968), Klebsiella pneumoniae 22.7% (n= 3334) and Enterobacter cloacae 6.9% (n= 1005) were the most prevalent isolates. Carbapenem resistance was detected in 894 isolates, and 5.8% (n= 412) of 7135 isolates isolated between October 2016 and September 2017; 6.4% (n= 482) of 7522 isolates between October 2017 and September 2018 were found to be resistant. Considering all isolates, colistin resistant isolates were 65 (0.9%) between October 2016 and September 2017 and 97 (1.3%) between October 2017 and September 2018. By including only the first isolates in the study for the same agent growths in different samples of the same patient, 46 colistin resistant isolates were selected. Six isolates which could not be cultivated from stock cultures were excluded from the study material. Thirteen (32.5%) of the 40 colistin resistant Enterobacterales isolates were isolated in 2017 and 27 (67.5%) were isolated in 2018. ESBL was detected in 22, AmpC beta-lactamase was detected in 6, carbapenem resistance was detected in 15 of them by phenotypic methods. As a result of PCR analysis, mcr-1 gene detected in 2 isolates, blaOXA-48 in 2 isolates, blaVIM in 1 isolate, blaKPC and blaOXA-48 in 1 isolate, blaNDM and blaOXA-48 in 5 isolates. These results were confirmed by sequencing of the PCR products. The mcr-1 genes were found in E.coli isolates grown in urine culture samples of 2 women over 65 years of age treated in our hospital. Among the antibiotics tested, only ampicillin resistance was observed in 1 of the patients, whereas ampicillin, amoxicillin-clavulanate and ciprofloxacin resistance were detected in the other. In conclusion, as far as we can reach in the literature our publication is the first study showing the presence of mcr-1 gene in clinical samples in our country and confirmed by DNA sequence analysis. The detection of mcr gene in isolates without multidrug resistance showed once again the importance of colistin susceptibility testing in the laboratories. In addition, the presence of isolates containing more than one resistance genes in our study, suggests that the spread of carbapenem and colistin resistance may be faster than expected.


Assuntos
Colistina , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae , Plasmídeos , Idoso , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Alemanha , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Estudos Retrospectivos
18.
BMC Infect Dis ; 20(1): 452, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600270

RESUMO

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Neoplasias/microbiologia , Idoso , Antibacterianos/farmacologia , China/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
19.
BMC Infect Dis ; 20(1): 540, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703276

RESUMO

BACKGROUND: Antimicrobial resistance is an ecological and multicausal problem. Infections caused by extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E) can be acquired and transmitted in the community. Data on community-associated ESBL-E infections/colonizations in Colombia are scarce. Georeferencing tools can be used to study the dynamics of antimicrobial resistance at the community level. METHODS: We conducted a study of geographic mapping using modern tools based on geographic information systems (GIS). Two study centers from the city of Pereira, Colombia were involved. The records of patients who had ESBL-producing Enterobacteriaceae were reviewed. Antimicrobial susceptibility testing and phenotypic detection of ESBL was done according to CLSI standards. RESULTS: A population of 415 patients with community-acquired infections/colonizations and 77 hospital discharges were obtained. Geographic distribution was established and heat maps were created. Several hotspots were evidenced in some geographical areas of the south-west and north-east of the city. Many of the affected areas were near tertiary hospitals, rivers, and poultry industry areas. CONCLUSIONS: There are foci of antimicrobial resistance at the community level. This was demonstrated in the case of antimicrobial resistance caused by ESBL in a city in Colombia. Causality with tertiary hospitals in the city, some rivers and the poultry industry is proposed as an explanation of the evidenced phenomenon. Geographic mapping tools are useful for monitoring antimicrobial resistance in the community.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Mapeamento Geográfico , Fenótipo , beta-Lactamases/genética , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Colômbia/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
20.
PLoS One ; 15(7): e0236106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673362

RESUMO

Alfalfa is a forage legume commonly associated with ruminant livestock production that may be a potential source of health-promoting phytochemicals. Anecdotal evidence from producers suggests that later cuttings of alfalfa may be more beneficial to non-ruminants; however, published literature varies greatly in measured outcomes, supplement form, and cutting. The objective of this study was to measure body weight, average daily feed intake, host immunity, and the colon microbiota composition in mice fed hay, aqueous, and chloroform extracts of early (1st) and late (5th) cutting alfalfa before and after challenge with Citrobacter rodentium. Prior to inoculation, alfalfa supplementation did not have a significant impact on body weight or feed intake, but 5th cutting alfalfa was shown to improve body weight at 5- and 6-days post-infection compared to 1st cutting alfalfa (P = 0.02 and 0.01). Combined with the observation that both chloroform extracts improved mouse body weight compared to control diets in later stages of C. rodentium infection led to detailed analyses of the immune system and colon microbiota in mice fed 1st and 5th cutting chloroform extracts. Immediately following inoculation, 5th cutting chloroform extracts significantly reduced the relative abundance of C. rodentium (P = 0.02) and did not display the early lymphocyte recruitment observed in 1st cutting extract. In later timepoints, both chloroform extracts maintained lower splenic B-cell and macrophage populations while increasing the relative abundance of potentially beneficially genera such as Turicibacter (P = 0.02). At 21dpi, only 5th cutting chloroform extracts increased the relative abundance of beneficial Akkermansia compared to the control diet (P = 0.02). These results suggest that lipid soluble compounds enriched in late-cutting alfalfa modulate pathogen colonization and early immune responses to Citrobacter rodentium, contributing to protective effects on body weight.


Assuntos
Citrobacter rodentium/fisiologia , Colo/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Lipídeos/química , Medicago sativa/química , Extratos Vegetais/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Colo/microbiologia , Citocinas/biossíntese , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/uso terapêutico , Solubilidade
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