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1.
Microbiol Mol Biol Rev ; 85(3): e0006421, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34076506

RESUMO

Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii toxins TcsL and TcsH, Clostridium novyi toxin TcnA, and Clostridium perfringens toxin TpeL. Since the 19th century, LCT-secreting bacteria have been isolated from the blood, organs, and wounds of diseased individuals, and LCTs have been implicated as the primary virulence factors in a variety of infections, including C. difficile infection and some cases of wound-associated gas gangrene. Clostridia express and secrete LCTs in response to various physiological signals. LCTs invade host cells by binding specific cell surface receptors, ultimately leading to internalization into acidified vesicles. Acidic pH promotes conformational changes within LCTs, which culminates in translocation of the N-terminal glycosyltransferase and cysteine protease domain across the endosomal membrane and into the cytosol, leading first to cytopathic effects and later to cytotoxic effects. The focus of this review is on the role of LCTs in infection and disease, the mechanism of LCT intoxication, with emphasis on recent structural work and toxin subtyping analysis, and the genomic discovery and characterization of LCT homologues. We provide a comprehensive review of these topics and offer our perspective on emerging questions and future research directions for this enigmatic family of toxins.


Assuntos
Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Clostridioides difficile/genética , Clostridium/genética , Animais , Infecções por Clostridium/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Humanos
2.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066903

RESUMO

The effect of effective microorganisms (EM) on internal organ morphology, intestinal morphometry, and serum biochemical activity in Japanese quails under Clostridium perfringens challenge was determined. After 30 days of EM addition, one group of quails was orally inoculated with Clostridium perfringens. The second group did not receive EM and was inoculated with C. perfringens. In the gut, EM supplementation reduced the number of lesions, enhanced gut health, and protected the mucosa from pathogenic bacteria. EM showed an anti-inflammatory effect and fewer necrotic lesions in villi. In the internal organs, EM showed a protective effect against a typical lesion of C. perfringens infection. Necrosis and degeneration of the hepatocytes, necrosis of bile ducts, and bile duct proliferation were more severe in the infected group without EM. Morphometric evaluation showed significantly higher villi in the jejunum after EM addition. A greater crypt depth was observed in the C. perfringens group. Biochemical analysis of the blood indicated lower cholesterol on the 12th day of the experiment and between-group differences in total protein, lactate dehydrogenase (LDH), and albumin levels in the EM group. Further studies are needed to improve EM activity against pathologic bacteria as a potential alternative to antibiotics and to develop future natural production systems.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças das Aves/sangue , Doenças das Aves/dietoterapia , Infecções por Clostridium/sangue , Infecções por Clostridium/dietoterapia , Clostridium perfringens , Enterite/sangue , Enterite/dietoterapia , Mucosa Intestinal/microbiologia , Probióticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Codorniz/sangue , Codorniz/microbiologia , Ração Animal/microbiologia , Animais , Ductos Biliares/patologia , Doenças das Aves/microbiologia , Colesterol/sangue , Infecções por Clostridium/microbiologia , Enterite/microbiologia , Feminino , Hepatócitos/patologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , L-Lactato Desidrogenase/sangue , Necrose , Albumina Sérica/análise , Resultado do Tratamento
3.
Ann Agric Environ Med ; 28(2): 224-230, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184502

RESUMO

The issue of patient safety during the provision of health services poses a key challenge in health policy. The number of hospital-acquired infections (also known as HAI - Healthcare Associated Infection) determines the level of quality of health services provided in a given health facility. Effective management reinforced by the awareness of a team of medical professionals allows not only reduction in the hospital's finances, but also the frequency of adverse events, which undoubtedly include hospital-acquired infections. Good cooperation between departments and a Hospital Infection Control Committee is one of the key aspects that translates to the rapid identification of new epidemic outbreaks. Infections caused by strains of Clostridium difficile (CDI, Clostridium difficile infection) are one of the main factors responsible for the prolonged hospitalization of patients. In the United States, Clostridium difficile causes almost half a million infections annually, and its treatment costs are estimated at nearly $ 4.8 billion per year. In Poland, the number of CDI cases in 2018 was 11.592 (for comparison, in 2013 the number of infections caused by this bacterium was 4.728). Hospital environment, inappropriate antibiotic therapy and development of multi-drug resistant strains increase the risk of infections. In order to improve the safety of hospitalized patients, infection risk management should be a systemic, formalized activity integrated with the overall process of managing a health facility. It is necessary that central units have interest in creating effective tools to enable successful epidemiological supervision and the implementation of strategic assumptions of health policy in this area.


Assuntos
Clostridioides difficile/fisiologia , Infecções por Clostridium/prevenção & controle , Infecção Hospitalar/prevenção & controle , Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Instalações de Saúde/estatística & dados numéricos , Humanos , Polônia/epidemiologia
4.
Am J Gastroenterol ; 116(9): 1954-1956, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34140459

RESUMO

INTRODUCTION: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown. METHODS: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted. RESULTS: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted. DISCUSSION: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children.


Assuntos
COVID-19 , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Padrões de Prática Médica , SARS-CoV-2/isolamento & purificação , Criança , Infecções por Clostridium/microbiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Estados Unidos
5.
Mayo Clin Proc ; 96(8): 2192-2204, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34175104

RESUMO

Clostridioides difficile infection is the most common cause of infectious diarrhea in hospitals with an increasing incidence in the community. Clinical presentation of C difficile infection ranges from diarrhea manageable in the outpatient setting to fulminant infection requiring intensive care admission. There have been significant advances in the management of primary and recurrent C difficile infection including diagnostics, newer antibiotics, antibody treatments, and microbiome restoration therapies. Because of the risk of clinical false-positive results with the polymerase chain reaction test, a two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C difficile toxin is being used. Cost permitting, I treat a first episode of C difficile infection preferably with fidaxomicin over vancomycin but not metronidazole. The most common complication after C difficile infection is recurrence. I manage a first recurrence with a vancomycin taper and pulse or fidaxomicin and recommend a single dose of intravenous bezlotoxumab (a monoclonal antibody against the toxin B) to reduce recurrence rates for those patients at high risk. Patients with multiply recurrent C difficile infection are managed with a course of antibiotics such as vancomycin or fidaxomicin followed by microbiota restoration. The success of fecal microbiota transplantation is greater than 85%, compared with the 40% to 50% success rate of antibiotics in this situation. Fecal microbiota transplantation is heterogeneous and has rare but serious risks such as transmission of infections. Standardized microbiota restoration therapies are in clinical development and have completed phase III clinical trials. This review answers common clinical questions in the management of C difficile infection.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Clostridium/terapia , Clostridium/isolamento & purificação , Transplante de Microbiota Fecal/métodos , Infecções por Clostridium/microbiologia , Humanos
6.
BMC Infect Dis ; 21(1): 456, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34016040

RESUMO

BACKGROUND: Clostridioides difficile is a Gram-positive anaerobic bacterium, which causes Clostridioides difficile infection (CDI). It has been recognised as a leading cause of healthcare-associated infections and a considerable threat to public health globally. This systematic literature review (SLR) summarises the current evidence on the epidemiology and clinical burden of CDI. METHODS: A SLR was conducted to identify CDI and recurrent CDI (rCDI) epidemiology studies, to evaluate patient and disease characteristics, incidence rates, epidemiological findings and risk factors. Embase, MEDLINE and the Cochrane Library databases were searched for English articles from 2009 to 2019. Included territories were the United Kingdom, France, Germany, Italy, Spain, Poland, US, Canada, Australia, Japan and China. RESULTS: Of 11,243 studies identified, 165 fulfilled the selection criteria. An additional 20 studies were identified through targeted review of grey literature. The most widely reported findings were incidence and risk factors for CDI and rCDI. Among key studies reporting both healthcare-associated (HA-CDI) and community-associated CDI (CA-CDI) incidence rates for each country of interest, incidence rates per 10,000 patient days in the US were 8.00 and 2.00 for HA-CDI and CA-CDI, respectively. The highest incidence in Europe was reported in Poland (HA-CDI: 6.18 per 10,000 patient days, CA-CDI: 1.4 per 10,000 patient days), the lowest from the UK, at 1.99 per 10,000 patient days and 0.56 per 10,000 patient days for HA-CDI and CA-CDI, respectively. No clear trend for incidence over time emerged, with most countries reporting stable rates but some either a decrease or increase. Rates of recurrent CDI varied based on geographical setting. The rate of recurrence was lower in community-associated disease compared to healthcare-associated disease. Independent CDI risk factors identified common to both initial CDI and recurrent CDI included increasing age, antibiotic use, recent hospitalisation, and proton pump inhibitor (PPI) use. In addition, leukocyte count, length of hospital stays, and Charlson comorbidity index score featured as statistically significant risk factors for recurrent CDI, but these are not reported among the most common statistically significant risk factors for initial CDI. CONCLUSIONS: Despite considerable heterogeneity, evidence suggests substantial incidence of recurrent and primary CDI, even after considerable efforts in the last decade.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Saúde Global , Humanos
7.
BMC Infect Dis ; 21(1): 462, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020604

RESUMO

BACKGROUND: Clostridioides difficile usually causes intestinal infections. However, a 75-year-old lady had a periprosthetic joint infection due to this microorganism. We report a C. difficile infection of a prosthetic hip joint. Such an infection is rarely reported around the world. CASE PRESENTATION: The elder female patient presented with a 2-year history of right hip pain with movement restriction. Her right leg was shorter than another. The skin around the right hip joint was red and swollen without sinus. Her lab test result showed elevator ESR and CRP. Her X-ray film showed a massive bone defect. The patient had a total hip arthroplasty 16 years ago and had a revision 5 years ago. During this hospitalization, her cultures of the synovial fluid and tissue repeatedly grew C. difficile. She improved following two-stage revision surgery and antibiotic treatment. The patient has no recurrence of infection after a one-year follow-up. CONCLUSION: A rapid and accurate sample collection is significant for culture results, making an outstanding contribution to the successful treatment.


Assuntos
Artroplastia de Quadril/efeitos adversos , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium , Infecções Relacionadas à Prótese , Reoperação/efeitos adversos , Adolescente , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , China , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Infecções por Clostridium/cirurgia , Feminino , Articulação do Quadril/microbiologia , Articulação do Quadril/cirurgia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgia , Líquido Sinovial/microbiologia , Resultado do Tratamento
8.
Am J Gastroenterol ; 116(4): 647-656, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33982930

RESUMO

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.


Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/métodos , Infecções por Clostridium/microbiologia , Fezes/microbiologia , Humanos , Recidiva
9.
Anaerobe ; 70: 102384, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34029702

RESUMO

Testing for and incidence of Clostridioides difficile infection (CDI) was examined at a single center before and during the first surge of the COVID-19 pandemic. Incidence of CDI remained stable but testing statistically significantly decreased during the first surge despite an increase in antibiotic use. There were no new CDI-focused antimicrobial stewardship interventions introduced during this time.


Assuntos
COVID-19/epidemiologia , Clostridioides difficile/fisiologia , Infecções por Clostridium/diagnóstico , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Humanos , Pandemias
10.
Food Microbiol ; 98: 103781, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33875209

RESUMO

An increasing proportion of Clostridioides difficile infections (CDI) are community acquired. This study tested farm, abattoir and retail food samples for C. difficile, using peer reviewed culture and molecular methods. The contamination rate on beef, sheep and broiler farms ranged from 2/30 (7%) to 25/30 (83%) in faeces, soil and water samples, while concentrations ranged from 2.9 log10 cfu/ml to 8.4 log10 cfu/g. The prevalence and associated counts were much lower in abattoir samples. Although 26/60 were C. difficile positive by enrichment and PCR, only 6 samples yielded counts by direct plating (1.1 log10 cfu/cm2 to 5.1 log10 cfu/g). At retail, 9/240 samples were C. difficile positive, including corned beef (1), spinach leaves (2), iceberg lettuce, little gem lettuce, wild rocket, coleslaw, whole milk yogurt and cottage cheese (1 sample each), with counts of up to 6.8 log10 cfu/g. The tcdA, tcdB, cdtA, cdtB, tcdC and tcdR genes were detected in 41%, 99.2%, 33.6%, 32%, 46.7% and 31.1%, respectively, of the 122 C. difficile isolates obtained. It was concluded that although the prevalence of C. difficile decreased along the food chain, retail foods were still heavily contaminated. This pathogen may therefore be foodborne, perhaps necessitating dietary advice for potentially vulnerable patients.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/veterinária , Contaminação de Alimentos/estatística & dados numéricos , Carne/microbiologia , Verduras/microbiologia , Matadouros/estatística & dados numéricos , Animais , Bovinos , Galinhas , Clostridioides difficile/classificação , Clostridioides difficile/genética , Clostridioides difficile/crescimento & desenvolvimento , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Qualidade de Produtos para o Consumidor , Fazendas/estatística & dados numéricos , Fezes/microbiologia , Contaminação de Alimentos/análise , Contaminação de Alimentos/economia , Humanos , Irlanda/epidemiologia , Carne/economia , Ovinos , Verduras/economia
11.
Nat Commun ; 12(1): 2240, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854064

RESUMO

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk.


Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Idoso , Biomarcadores/análise , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Clostridioides difficile/genética , Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Quimioterapia Combinada , Feminino , Fluoroquinolonas/uso terapêutico , Seguimentos , Microbioma Gastrointestinal , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Estudos Prospectivos
12.
Nat Commun ; 12(1): 2241, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854066

RESUMO

Antibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset. We show that patients developing CDI already exhibit significantly lower diversity before antibiotic treatment and a distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients. We find that antibiotic treatment-induced dysbiosis is class-specific with beta-lactams further increasing enterococcal abundance. Our findings, validated in an independent prospective patient cohort developing CDI, can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive microbiota-based diagnostics for management of patients at risk for CDI.


Assuntos
Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Microbioma Gastrointestinal , Idoso , Antibacterianos/uso terapêutico , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biomarcadores/análise , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806791

RESUMO

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.


Assuntos
Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Peptídeos/farmacologia , Antibacterianos/química , Antifúngicos/farmacologia , Bacteriocinas/química , Biofilmes/efeitos dos fármacos , Clostridiales/metabolismo , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Clostridium perfringens/efeitos dos fármacos , Humanos , Peptídeos/química , Processamento de Proteína Pós-Traducional
14.
Toxins (Basel) ; 13(4)2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917845

RESUMO

Clostridium perfringens enterotoxin (CPE) regularly causes food poisoning and antibiotic-associated diarrhea; therefore, reliable toxin detection is crucial. To this aim, we explored stationary and mobile strategies to detect CPE either exclusively by monoclonal antibodies (mAbs) or, alternatively, by toxin-enrichment via the cellular receptor of CPE, claudin-4, and mAb detection. Among the newly generated mAbs, we identified nine CPE-specific mAbs targeting five distinct epitopes, among them mAbs recognizing CPE bound to claudin-4 or neutralizing CPE activity in vitro. In surface plasmon resonance experiments, all mAbs and claudin-4 revealed excellent affinities towards CPE, ranging from 0.05 to 2.3 nM. Integrated into sandwich enzyme-linked immunosorbent assays (ELISAs), the most sensitive mAb/mAb and claudin-4/mAb combinations achieved similar detection limits of 0.3 pg/mL and 1.0 pg/mL, respectively, specifically detecting recombinant CPE from spiked feces and native CPE from 30 different C. perfringens culture supernatants. The implementation of mAb- and receptor-based ELISAs into a mobile detection platform enabled the fast detection of CPE, which will be helpful in clinical laboratories to diagnose diarrhea of assumed bacterial origin. In conclusion, we successfully employed an endogenous receptor and novel high affinity mAbs for highly sensitive and specific CPE-detection. These tools will be useful for both basic and applied research.


Assuntos
Anticorpos Monoclonais , Claudina-4/metabolismo , Infecções por Clostridium/diagnóstico , Clostridium perfringens/metabolismo , Enterotoxinas/análise , Ensaio de Imunoadsorção Enzimática , Doenças Transmitidas por Alimentos/diagnóstico , Animais , Afinidade de Anticorpos , Especificidade de Anticorpos , Automação Laboratorial , Claudina-4/genética , Claudina-4/imunologia , Infecções por Clostridium/microbiologia , Clostridium perfringens/genética , Clostridium perfringens/imunologia , Enterotoxinas/genética , Enterotoxinas/imunologia , Enterotoxinas/metabolismo , Mapeamento de Epitopos , Epitopos , Fezes , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Limite de Detecção , Camundongos , Valor Preditivo dos Testes , Ligação Proteica , Reprodutibilidade dos Testes , Fluxo de Trabalho
15.
Zoonoses Public Health ; 68(5): 431-442, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33878232

RESUMO

The current study is undertaken to characterize the prevalence, genotypes distribution, antibiotic resistance and genetic diversity of Clostridium perfringens (C. perfringens) collected from different stages of a chicken production chain. In total, 579 samples from a broiler farm and 378 samples from the slaughterhouse were collected from a large-scale rearing and slaughter one-stop enterprise in Weifang, China, between June and July 2019, of which 30.40% of the samples from farm and 54.50% of samples from slaughterhouse were determined to be positive for C. perfringens, respectively. The contamination of chicken products was relatively serious, with the total positive rate of carcasses at 59.73%; the positive rate of carcass samples was the highest in the evisceration process, which might be the critical point of C. perfringens contamination. A total of 476 isolates of C. perfringens were recovered; and 99.58% of recovered isolates were identified as type A, with the remaining isolates being type G. Antimicrobial susceptibility testing revealed that 97.15% of the isolates showed multiple antibiotic resistance and 67.89% of them were resistant to at least five classes of commonly used antibiotics. Multilocus sequence typing results of 91 representative isolates showed that the isolates can be divided into 74 sequences types (STs); 40.66% of the isolates can be included into seven clonal complexes (CCs). Although most of the isolates were classified as type A, considerable genetic diversity was observed, with the Simpson's diversity index of ST up to 0.9902. Some isolates from farm stage and slaughter stage were distributed in the same ST or CC, indicating that chicken products may be contaminated by the same ST or CC of C. perfringens originated from the farm stage. The high contamination rates of chicken products and the widespread multiple antibiotic resistance of isolates indicated potential public health risks, control measures at rearing and slaughtering stage should be considered to reduce this risk.


Assuntos
Galinhas/microbiologia , Infecções por Clostridium/veterinária , Clostridium perfringens , Tipagem de Sequências Multilocus/veterinária , Doenças das Aves Domésticas/microbiologia , Matadouros , Animais , Infecções por Clostridium/microbiologia , Clostridium perfringens/classificação , Fazendas , Zoonoses
16.
Lett Appl Microbiol ; 73(2): 149-158, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33864273

RESUMO

Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71·6% vs 40·2%, and 35·3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0·74 (95% CI of -0·9 to -0·58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0·44 (95% CI of 0·20-0·69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.


Assuntos
Infecções por Clostridium/terapia , Diarreia/terapia , Transplante de Microbiota Fecal/métodos , Administração Oral , Cápsulas/administração & dosagem , Clostridioides difficile , Infecções por Clostridium/microbiologia , Diarreia/microbiologia , Enema , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal , Humanos , Resultado do Tratamento
17.
Nature ; 593(7858): 261-265, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33911281

RESUMO

Several enteric pathogens can gain specific metabolic advantages over other members of the microbiota by inducing host pathology and inflammation. The pathogen Clostridium difficile is responsible for a toxin-mediated colitis that causes 450,000 infections and 15,000 deaths in the United States each year1; however, the molecular mechanisms by which C. difficile benefits from this pathology remain unclear. To understand how the metabolism of C. difficile adapts to the inflammatory conditions that its toxins induce, here we use RNA sequencing to define, in a mouse model, the metabolic states of wild-type C. difficile and of an isogenic mutant that lacks toxins. By combining bacterial and mouse genetics, we demonstrate that C. difficile uses sorbitol derived from both diet and host. Host-derived sorbitol is produced by the enzyme aldose reductase, which is expressed by diverse immune cells and is upregulated during inflammation-including during toxin-mediated disease induced by C. difficile. This work highlights a mechanism by which C. difficile can use a host-derived nutrient that is generated during toxin-induced disease by an enzyme that has not previously been associated with infection.


Assuntos
Toxinas Bacterianas/metabolismo , Clostridioides difficile/metabolismo , Clostridioides difficile/patogenicidade , Infecções por Clostridium/metabolismo , Infecções por Clostridium/microbiologia , Interações Hospedeiro-Patógeno , Sorbitol/metabolismo , Aldeído Redutase/metabolismo , Animais , Toxinas Bacterianas/biossíntese , Toxinas Bacterianas/genética , Clostridioides difficile/genética , Infecções por Clostridium/enzimologia , Colite/enzimologia , Colite/metabolismo , Colite/microbiologia , Feminino , Regulação Bacteriana da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação
18.
Infect Immun ; 89(5)2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33649048

RESUMO

Infection with the bacterial pathogen Clostridioides difficile causes severe damage to the intestinal epithelium that elicits a robust inflammatory response. Markers of intestinal inflammation accurately predict clinical disease, however, the extent to which host-derived proinflammatory mediators drive pathogenesis versus promote host protective mechanisms remains elusive. In this report, we employed Il10 -/- mice as a model of spontaneous colitis to examine the impact of constitutive intestinal immune activation, independent of infection, on C. difficile disease pathogenesis. Upon C. difficile challenge, Il10 -/- mice exhibited significantly decreased morbidity and mortality compared to littermate Il10 heterozygote (Il10 HET) control mice, despite a comparable C. difficile burden, innate immune response, and microbiota composition following infection. Similarly, antibody-mediated blockade of interleukin-10 (IL-10) signaling in wild-type C57BL/6 mice conveyed a survival advantage if initiated 3 weeks prior to infection. In contrast, no advantage was observed if blockade was initiated on the day of infection, suggesting that the constitutive activation of inflammatory defense pathways prior to infection mediated host protection. IL-22, a cytokine critical in mounting a protective response against C. difficile infection, was elevated in the intestine of uninfected, antibiotic-treated Il10 -/- mice, and genetic ablation of the IL-22 signaling pathway in Il10 -/- mice negated the survival advantage following C. difficile challenge. Collectively, these data demonstrate that constitutive loss of IL-10 signaling, via genetic ablation or antibody blockade, enhances IL-22-dependent host defense mechanisms to limit C. difficile pathogenesis.


Assuntos
Clostridioides difficile/fisiologia , Infecções por Clostridium/metabolismo , Infecções por Clostridium/microbiologia , Interações Hospedeiro-Patógeno , Interleucina-10/metabolismo , Interleucinas/metabolismo , Transdução de Sinais , Animais , Infecções por Clostridium/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Knockout
19.
Diagn Microbiol Infect Dis ; 100(2): 115346, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33647544

RESUMO

INTRODUCTION: It is common among microbiology laboratories to blind the Clostridioides difficile (C. difficile) BioFire FilmArray GI Panel result in fear of overdiagnosis. METHODS: We examined the rate of missed community-onset C. difficile infection (CDI) diagnosis and associated outcomes. Adult patients with FilmArray GI Panel positive for C. difficile on hospital admission who lacked dedicated C. difficile testing were included. RESULTS: Among 144 adults with a FilmArray Panel positive for C. difficile, 18 did not have concurrent dedicated C. difficile testing. Eight patients were categorized as possible, 5 as probable and 4 as definite cases of missed CDI diagnosis. We observed associated delays in initiation of appropriate therapy, intensive care unit admissions, hospital readmissions, colorectal surgery and death/discharge to hospice. Five out of 17 lacked risk factors for CDI. CONCLUSION: The practice of concealing C. difficile FilmArray GI Panel results needs to be reconsidered in patients presenting with community-onset colitis.


Assuntos
Clostridioides difficile , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Reação em Cadeia da Polimerase Multiplex/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Emerg Microbes Infect ; 10(1): 687-699, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33682630

RESUMO

Clostridioides difficile is the predominant antibiotic-associated enteropathogen associated with diarrhoea or pseudomembranous colitis in patients worldwide. Previously, we identified C. difficile RT078 isolates (CD21062) from elderly patients in China, including two new ribotype strains (CD10010 and CD12038) belonging to the ST11 group, and their genomic features were also investigated. This study compared sporulation, spore germination, toxin expression, flagellar characteristics, and adhesion among these strains in vitro and analysed their pathogenic ability in vivo using animal models. The results showed sporulation and spore germination did not significantly differ among the three C. difficile strains. CD10010 and CD12038 showed higher transcriptional levels of toxins until 48 h; thereafter, the transcriptional levels of toxins remained constant among RT078, CD10010, and CD12038. RT078 showed a loss of flagellum and its related genes, whereas CD12038 showed the highest motility in vitro. Both CD10010 and CD12038 initially showed flg phase OFF, and the flagellar switch reversed to phase ON after 48 h in swim agar. Flagellar proteins and toxins were both upregulated when flg phase OFF changed to flg phase ON status, enhancing their pathogenic ability. CD12038 showed the highest adhesion to Hep-2 cells. Histopathology and inflammation scores demonstrated that CD12038 caused the most severe tissue damage and infection in vivo. The new ribotype strains, particularly CD12038, exhibit higher pathogenic ability than the typical RT078 strain, both in vitro and in vivo. Therefore, more attention should be paid to this new C. difficile strain in epidemiological research; further studies are warranted.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , China , Clostridioides difficile/classificação , Clostridioides difficile/genética , Clostridioides difficile/crescimento & desenvolvimento , Enterocolite Pseudomembranosa/microbiologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Esporos Bacterianos/genética , Esporos Bacterianos/crescimento & desenvolvimento , Esporos Bacterianos/metabolismo , Tupaiidae , Virulência
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