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1.
Int J Antimicrob Agents ; 55(3): 105887, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926283

RESUMO

The STEP surveillance study was designed to increase knowledge about distribution of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa in Portugal, focusing on the intensive care unit (ICU). Antimicrobial susceptibility of common agents was also evaluated and compared with that of one of the latest therapeutic introductions, ceftolozane-tazobactam (C/T). Clinical isolates of Enterobacterales (n=426) and P. aeruginosa (n=396) from patients admitted in Portuguese ICUs were included. Activity of C/T and comparators was investigated using standard broth microdilution. Isolates were recovered from urinary tract (UTI, 36.9%), intra-abdominal (IAI, 24.2%) and lower respiratory tract (LRTI, 38.9%) infections. In P. aeruginosa, overall distribution of MDR/extremely-drug resistant (XDR)/pan-drug resistant (PDR) isolates accounted for 21.2%, 23.2% and 0.8%, respectively. C/T was the most potent agent tested against P. aeruginosa and MDR/XDR/PDR phenotypes. In Escherichia coli, extended-spectrum beta-lactamases (ESBL) and carbapenemase (CP) phenotypes accounted for 16.6% and 1.7%, respectively, whereas in Klebsiella spp., ESBL and CP-phenotypes represented 28.5% and 17.9%, respectively. Overall, susceptibility of C/T against Enterobacterales was 86.9%. C/T was the least affected agent in E. coli (99.4% susceptibility), whereas its activity was moderate in Klebsiella spp. (71.5%) and Enterobacter spp. (70.4%), due in part to a high rate of ESBL and CP-phenotypes. In Enterobacterales, blaKPC was the most prevalent CP gene (63.0%), followed by blaOXA-48 (33.3%) and blaVIM (3.7%). These microbiological results reinforce C/T as a therapeutic option in ICU patients with UTI, IAI or LRTI due to P. aeruginosa or Enterobacterales isolates, but not for CP producers.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções Intra-Abdominais/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Tazobactam/farmacologia , Infecções Urinárias/tratamento farmacológico , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , Unidades de Terapia Intensiva , Portugal , Infecções por Pseudomonas/microbiologia , Tazobactam/uso terapêutico
2.
Int J Antimicrob Agents ; 55(3): 105896, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927042

RESUMO

A previous soil metagenomics study recovered a novel cephalosporin resistance determinant, pbpTET A6, for which the exact resistance mechanism was unclear. This study used a three-dimensional structure-guided mutagenesis approach to demonstrate that PBPTET A6 is likely to be a class A penicillin-binding protein (PBP), and that its ability to confer cephalosporin resistance is directly linked to the functional integrity of its transpeptidase (TP) catalytic core. Screening of a library of PBPTET A6 variants carrying randomly introduced point mutations revealed additional residue modifications that compromised resistance, all of which were proximal to the TP active site except one which was found in a 29-amino-acid-long superstructure (α6-α7 loop) absent in other class A PBP homologues. Based on the site-specific mutagenesis results, it is hypothesized that residue arginine-400 plays an important role in limiting the access of certain cephalosporin compounds to the enzymatic core of the TP domain of PBPTET A6. Using a combination of adaptive evolution assays and whole-genome sequencing, the potential impact of PBPTET A6 on promoting the development of resistance in the clinically significant opportunistic pathogen Pseudomonas aeruginosa was investigated. Under the selective pressure of serial ceftazidime exposures, the pbpTET A6-expressing P. aeruginosa population readily evolved by excluding a ~400-kbp chromosomal element to acquire additional resistance against cephalosporins, suggesting that PBPTET A6 has a catalytic effect on facilitating antibiotic-resistance-associated genome adaptation. Overall, the soil environment contains genes conferring resistance to critically important antibiotics by cryptic mechanisms. Understanding what impact anthropogenic activities might have on the abundance and evolution of these genes should be a priority.


Assuntos
Proteínas de Bactérias/genética , Resistência às Cefalosporinas/genética , Proteínas de Ligação às Penicilinas/genética , Pseudomonas aeruginosa/genética , Genoma Bacteriano , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos
3.
J Med Microbiol ; 69(2): 162-175, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31935190

RESUMO

The advent of next-generation sequencing technology has revolutionized the field of prokaryotic genetics and genomics by allowing interrogation of entire genomes, transcriptomes and global transcription factor binding profiles. As more studies employing these techniques have been performed, the state of the art regarding prokaryotic gene regulation has developed from the level of individual genes to genetic regulatory networks and systems biology. When applied to bacterial pathogens, particularly valuable insights have been gained into the regulation of virulence-associated genes, their relative importance to bacterial survival in planktonic, biofilm or host infection scenarios, antimicrobial resistance and the molecular details of host-pathogen interactions. This review outlines some of the latest developments and applications of next-generation sequencing techniques that have used primarily Pseudomonas aeruginosa as a model system. We focus particularly on insights into Pseudomonas virulence and infection that have been gained from these approaches and the future directions in which this field could develop.


Assuntos
Proteínas de Bactérias/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Transcriptoma , Animais , Proteínas de Bactérias/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pseudomonas aeruginosa/fisiologia
4.
J Med Microbiol ; 69(2): 147-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31961787

RESUMO

During infections, bacterial pathogens can engage in a variety of interactions with each other, ranging from the cooperative sharing of resources to deadly warfare. This is especially relevant in opportunistic infections, where different strains and species often co-infect the same patient and interact in the host. Here, we review the relevance of these social interactions during opportunistic infections using the human pathogen Pseudomonas aeruginosa as a case example. In particular, we discuss different types of pathogen-pathogen interactions, involving both cooperation and competition, and elaborate on how they impact virulence in multi-strain and multi-species infections. We then review evolutionary dynamics within pathogen populations during chronic infections. We particuarly discuss how local adaptation through niche separation, evolutionary successions and antagonistic co-evolution between pathogens can alter virulence and the damage inflicted on the host. Finally, we outline how studying bacterial social dynamics could be used to manage infections. We show that a deeper appreciation of bacterial evolution and ecology in the clinical context is important for understanding microbial infections and can inspire novel treatment strategies.


Assuntos
Interações Microbianas , Infecções Oportunistas/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Animais , Coinfecção/microbiologia , Humanos , Pseudomonas aeruginosa/genética
5.
J Med Microbiol ; 69(2): 195-206, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31971503

RESUMO

Micro-organisms use quorum sensing (QS), a cell density-dependent process, to communicate. This QS mode of interchange leads to the production of a variety of virulence factors, co-ordination of complex bacterial behaviours, such as swarming motility, degradation of host tissue and biofilm formation. QS is implicated in numerous human infections and consequently researchers have sought ways of effectively inhibiting the process in pathogenic bacteria. Two decades ago, furanones were the first class of chemical compounds identified as Pseudomonas aeruginosa QS inhibitors (QSIs). P. aeruginosa is a ubiquitous organism, capable of causing a wide range of infections in humans, including eye and ear infections, wound infections and potentially fatal bacteraemia and thus novel treatments against this organism are greatly needed. This review provides a brief background on QS and the use of furanones as QSIs. Based on the effectiveness of action, both in vivo and in vitro, we will explore the use of furanones as potential antimicrobial therapeutics and conclude with open questions.


Assuntos
Antibacterianos/administração & dosagem , Furanos/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Animais , Antibacterianos/química , Furanos/química , Humanos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia
6.
J Med Microbiol ; 69(2): 207-217, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31976856

RESUMO

Introduction. Infections attributable to carbapenem-resistant Gram-negative bacilli are increasing globally. New antimicrobial agents are urgently needed to treat patients with these infections.Aim. To describe susceptibility to the novel carbapenem-ß-lactamase inhibitor combination imipenem-relebactam and comparators of clinical isolates of non-Proteeae Enterobacteriaceae (NPE) and Pseudomonas aeruginosa from intraabdominal infections (IAIs) and urinary tract infections (UTIs).Methods. Broth microdilution MICs were determined for isolates collected in 22 European countries in 2015-2017 and interpreted using EUCAST breakpoints; imipenem-relebactam MICs were interpreted using imipenem breakpoints.Results. For NPE, 98.4 % of isolates from IAIs (n=10,465) and 98.5 % of UTI isolates (n=7,446) were susceptible to imipenem-relebactam, as were 42.4 % of imipenem-nonsusceptible (n=474), 98.6 % of Klebsiella pneumoniae carbapenemase (KPC)-positive (n=138), and 93.9 % of multidrug-resistant (MDR) isolates (n=4,424) from IAIs and UTIs combined. Molecular analysis demonstrated that two-thirds of imipenem-nonsusceptible isolates rendered susceptible by relebactam carried KPCs; 96 % (261/271) of imipenem-nonsusceptible isolates of NPE that remained nonsusceptible in the presence of relebactam carried metallo-ß-lactamase (MBL)-type and/or OXA-48-like carbapenemases. Among P. aeruginosa, 94.4 % of IAI (n=1,245) and 93.0 % of UTI isolates (n=714) were susceptible to imipenem-relebactam, as were 74.4 % of imipenem-nonsusceptible (n=469) and 79.8 % of MDR isolates (n=595) from IAIs and UTIs combined. Among the 120 isolates of P. aeruginosa that remained nonsusceptible to imipenem upon addition of relebactam, 72 % carried MBLs. The distribution of NPE and P. aeruginosa carrying carbapenemases varied substantially across Europe, as did resistance to imipenem and imipenem-relebactam.Conclusions. Continued surveillance of antimicrobial resistance and resistance mechanisms, including the study of imipenem-relebactam as it approaches regulatory approval, appears warranted.


Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Imipenem/farmacologia , Infecções Intra-Abdominais/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Urinárias/microbiologia , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/fisiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Monitoramento Epidemiológico , Europa (Continente)/epidemiologia , Humanos , Infecções Intra-Abdominais/epidemiologia , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Infecções Urinárias/epidemiologia
7.
Nat Commun ; 11(1): 543, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992714

RESUMO

Health care-associated infections such as Pseudomonas aeruginosa bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a "dead-end" for P. aeruginosa and to have no impact on transmission. Here, we use a mouse infection model to show that P. aeruginosa can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. Our work shows that the gallbladder is crucial for spread of P. aeruginosa from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system. Further research is needed to test to what extent these findings are relevant to infections in patients.


Assuntos
Bacteriemia/microbiologia , Bacteriemia/transmissão , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/transmissão , Pseudomonas aeruginosa/patogenicidade , Animais , Bacteriemia/patologia , Modelos Animais de Doenças , Epitélio/microbiologia , Fezes/microbiologia , Feminino , Vesícula Biliar/microbiologia , Vesícula Biliar/patologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pneumonia/microbiologia , Infecções por Pseudomonas/patologia , Sistemas de Secreção Tipo III
8.
J Med Microbiol ; 69(1): 3-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31750813

RESUMO

Pseudomonas aeruginosa, a versatile Gram-negative pathogen that can cause a wide range of infections, is the most common causative agent in cases of bacterial keratitis associated with contact-lens use. Corneal infections with P. aeruginosa often have poor clinical outcomes and can result in long and costly treatments. During the infection process, the pathogen exploits its large genome, encoding complex regulatory networks and a wide range of virulence factors, including motility and the secretion of various proteases and toxins. Although antibiotic resistance levels in the UK are low, higher levels have been seen in some other countries. In the face of increasing antibiotic resistance, alternative therapeutic approaches such as antivirulence strategies and phage therapy are being developed. There is increasing evidence to suggest that keratitis infections are associated with a phylogenetic subgroup of P. aeruginosa isolates carrying the gene encoding the potent cytotoxin exotoxin U, one of two mutually exclusive exotoxins secreted via the type III secretion system. The mechanisms behind this association are unclear, but understanding the genetic differences that predispose P. aeruginosa to cause corneal infections may allow for the development of targeted and more effective future treatments to reduce the morbidity of P. aeruginosa keratitis. In order to minimize the risk of severe P. aeruginosa eye infections, a wide range of contact-lens disinfection solutions are available. Constant exposure to biocides at a range of concentrations, from sub-inhibitory to inhibitory, could contribute to the development of resistance to both antibiotics and disinfectants.


Assuntos
Lentes de Contato/efeitos adversos , Ceratite/epidemiologia , Ceratite/microbiologia , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Farmacorresistência Bacteriana , Exotoxinas/metabolismo , Genótipo , Saúde Global , Humanos , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/genética , Fatores de Virulência/metabolismo
9.
BMC Infect Dis ; 19(1): 1028, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795953

RESUMO

BACKGROUND: Pseudomonas aeruginosa-related pneumonia is an ongoing healthcare challenge. Estimating its financial burden is complicated by the time-dependent nature of the disease. METHODS: Two hundred thirty-six cases of Pseudomonas aeruginosa-related pneumonia were recorded at a 2000 bed German teaching hospital between 2011 and 2014. Thirty-five cases (15%) were multidrug-resistant (MDR) Pseudomonas aeruginosa. Hospital- and community-acquired cases were distinguished by main diagnoses and exposure time. The impact of Pseudomonas aeruginosa-related pneumonia on the three endpoints cost, reimbursement, and length of stay was analyzed, taking into account (1) the time-dependent nature of exposure, (2) clustering of costs within diagnostic groups, and (3) additional confounders. RESULTS: Pseudomonas aeruginosa pneumonia is associated with substantial additional costs that are not fully reimbursed. Costs are highest for hospital-acquired cases (€19,000 increase over uninfected controls). However, community-acquired cases are also associated with a substantial burden (€8400 when Pseudomonas aeruginosa pneumonia is the main reason for hospitalization, and €6700 when not). Sensitivity analyses for hospital-acquired cases showed that ignoring or incorrectly adjusting for time-dependency substantially biases results. Furthermore, multidrug-resistance was rare and only showed a measurable impact on the cost of community-acquired cases. CONCLUSIONS: Pseudomonas aeruginosa pneumonia creates a substantial financial burden for hospitals. This is particularly the case for nosocomial infections. Infection control interventions could yield significant cost reductions. However, to evaluate the potential effectiveness of different interventions, the time-dependent aspects of incremental costs must be considered to avoid introduction of bias.


Assuntos
Infecções Comunitárias Adquiridas/economia , Infecção Hospitalar/economia , Custos Hospitalares , Hospitalização/economia , Pneumonia Bacteriana/economia , Infecções por Pseudomonas/economia , Pseudomonas aeruginosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Feminino , Alemanha , Hospitais de Ensino , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia
10.
Rev Soc Bras Med Trop ; 53: e20180498, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31859938

RESUMO

INTRODUCTION: Pseudomonas aeruginosa is one of the main pathogens causing infection in intensive care units (ICUs) and usually presents antimicrobial resistance. METHODS: Data were obtained from ICUs between 2010 and 2013. RESULTS: P. aeruginosa had a prevalence of 14.5% of which 48.7% were multidrug resistant. We observed increasing resistance to carbapenems and polymyxin B and growing consumption of aminoglycosides, meropenem, ceftazidime, and polymyxin B. The regression impact between resistance and consumption was significant with respect to amikacin, imipenem, meropenem, and polymyxin B. CONCLUSIONS: Monitoring antimicrobial consumption and resistant microorganisms should be reinforced to combat antimicrobial- and multi-drug resistance.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Prevalência , Pseudomonas aeruginosa/isolamento & purificação
11.
PLoS Comput Biol ; 15(12): e1007562, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31860667

RESUMO

Pseudomonas aeruginosa, a main cause of human infection, can gain resistance to the antibiotic aztreonam through a mutation in NalD, a transcriptional repressor of cellular efflux. Here we combine computational analysis of clinical isolates, transcriptomics, metabolic modeling and experimental validation to find a strong association between NalD mutations and resistance to aztreonam-as well as resistance to other antibiotics-across P. aeruginosa isolated from different patients. A detailed analysis of one patient's timeline shows how this mutation can emerge in vivo and drive rapid evolution of resistance while the patient received cancer treatment, a bone marrow transplantation, and antibiotics up to the point of causing the patient's death. Transcriptomics analysis confirmed the primary mechanism of NalD action-a loss-of-function mutation that caused constitutive overexpression of the MexAB-OprM efflux system-which lead to aztreonam resistance but, surprisingly, had no fitness cost in the absence of the antibiotic. We constrained a genome-scale metabolic model using the transcriptomics data to investigate changes beyond the primary mechanism of resistance, including adaptations in major metabolic pathways and membrane transport concurrent with aztreonam resistance, which may explain the lack of a fitness cost. We propose that metabolic adaptations may allow resistance mutations to endure in the absence of antibiotics and could be targeted by future therapies against antibiotic resistant pathogens.


Assuntos
Farmacorresistência Bacteriana/genética , Mutação com Perda de Função , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Aztreonam/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Biologia Computacional , Perfilação da Expressão Gênica , Genes Bacterianos , Humanos , Redes e Vias Metabólicas , Modelos Biológicos , Modelos Moleculares , Filogenia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Análise de Sistemas
12.
Medicine (Baltimore) ; 98(44): e17786, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689851

RESUMO

RATIONALE: Grade 4 diabetic foot (DF) is a severe infection that causes bone destruction, osteomyelitis, and osteoarticular damage, which, in turn, can lead to serious dry or wet gangrene, or amputation. DF is extremely difficult to treat. PATIENT CONCERNS: A 71-year-old female patient with long-term diabetes complicated with uremia, who undergoes regular hemodialysis 2 to 3 times per week, was admitted with grade 4 DF with Pseudomonas aeruginosa infection, and concomitant vascular occlusion of the lower extremities. The patient had a concurrent nutrition and electrolyte disorder. DIAGNOSES: The patient was diagnosed with type 2 diabetes, grade 4 DF, postamputation of the 2nd toe, vascular occlusion of the lower extremities, atherosclerosis, uremia, hypoproteinemia, and electrolyte disturbances. INTERVENTIONS: Treatment with antibiotics and comprehensive measures aimed at improving nutrition and microcirculation, controlling blood glucose, as well as balancing electrolytes were performed to ameliorate the general conditions. Nibbled debridement was used to remove devitalized tissues each time to maintain as much vital cells as possible. Open therapy was used for necrotic tissues, and dressings therapy was used simultaneously for the infected lesion. This combined treatment, involving open therapy with dressing, is referred to as "semiclosure wound therapy." Negative pressure wound therapy (NPWT) was used after a fistula formed. OUTCOMES: During the treatment procedure, the gangrene 3rd toe was spontaneously shed; the necrotic 1st toe was removed by surgery. The wound gradually healed after 3 months of open therapy combined with dressing. High location amputation was avoided. LESSONS: Semiclosure, which constitutes open therapy combined with the use of dressings, plus NPWT can preserve vital skin cells in the wound and control the aggravation of the infection. It is an effective and novel measure that prevents DF amputation in old patient and promotes wound union.


Assuntos
Desbridamento/métodos , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Doenças Vasculares Periféricas/terapia , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa , Idoso , Antibacterianos/uso terapêutico , Bandagens , Terapia Combinada , Diabetes Mellitus Tipo 2/microbiologia , Feminino , Humanos , Doenças Vasculares Periféricas/microbiologia , Infecções por Pseudomonas/microbiologia
13.
Medicine (Baltimore) ; 98(44): e17812, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689866

RESUMO

The aim of this study was to analyze the risk factors, clinical features, and antimicrobial resistance of Pseudomonas putida (P putida) isolated from Tongji Hospital in Wuhan, China.The data of 44 patients with P putida infections were retrospectively reviewed in this study. All cases of P putida strains were detected by the clinical laboratory of Tongji Hospital in the period of January 2010 to December 2017. Antimicrobial susceptibility testing was conducted using Kirby-Bauer method.Forty-four effective strains of P putida were isolated, including 32 inpatients and 12 outpatients. The 32 inpatients cases were obtained from various departments, which were urosurgery wards (n = 5, 15.6%), pediatrics wards (n = 4, 12.5%), hepatic surgery wards (n = 4, 12.5%), among others. The isolates had been discovered from urine specimens (28.2%), blood specimens (21.9%), sputum specimens (12.5%), and so on. Twenty-five patients had histories of catheterization before the isolation of P putida. Twenty-four patients were in immunocompromised states, 5 patients had undergone surgery, catheterization and were taking immunosuppressive therapy simultaneously. Polymicrobial infections were found in some P putida cases, especially Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Escherichia coli. All the patients had treated by antimicrobial before culture. Multi-drug-resistant strains were detected in 75% of P putida isolates. The P putida strains were resistant to trimethoprim/sulfamethoxazole (97.7%), aztreonam (88.6%), minocyline (74.3%), ticarcillin/clavulanic acid (72.7%), and sensitive to amikacin (86.4%), imipenem (62.8%), gentamicin (56.8%).Catheterization or other invasive procedures, immunocompromised states, and underlying diseases increased the risks of P putida infections. Moreover, the P putida strains were highly resistant to trimethoprim/sulfamethoxazole, aztreonam, minocyline, ticarcillin/clavulanic acid.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Pseudomonas/microbiologia , Pseudomonas putida/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
Emerg Microbes Infect ; 8(1): 1658-1667, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31718472

RESUMO

Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in P. aeruginosa, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the prrH locus sRNA influences P. aeruginosa virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of P. aeruginosa in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the rhl QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the rhl system, on the promoter region of prrH. Further ß-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to P. aeruginosa pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in P. aeruginosa and provide new insight into PrrH's function.


Assuntos
Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/patogenicidade , RNA Bacteriano/metabolismo , Proteínas de Bactérias/genética , Humanos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum , RNA Bacteriano/genética , Virulência
15.
BMC Complement Altern Med ; 19(1): 315, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744500

RESUMO

BACKGROUND: Pseudomonas aeruginosa has become a main cause of Gram-negative infection, particularly in patients with compromised immunity. High rates of resistance to antibiotics are associated with nosocomial infections caused by P. aeruginosa strains. The search for novel antimicrobials has been necessitated by the emergence of antimicrobial resistance in some bacteria Plant-based antimicrobials has great potential to combat microbial infections using a variety of mechanisms. Triumfetta welwitschii plant roots are traditionally used to treat symptoms of diarrhoea and fever, suggesting that it possess antimicrobial and immunomodulatory effects. Since research investigating antimicrobial properties of the roots of Triumfetta welwitschii has been explored, there is need to investigate the antimicrobial activity of its leaf extracts in order to probe their prospective use as new antimicrobial agents that can be used to combat nosocomial infections. The objective of this study was to evaluate the antibacterial activities, the mode of action and cytotoxicity of T. welwitschii leaf extracts. METHOD: Extracts of T. welwitschii leaves were obtained using eight different solvents, the serial exhaustive extraction method and the cold maceration technique. In vitro antibacterial activity evaluation of the extracts was done on eight bacterial isolates using the broth microdilution method. The mode of action for the most potent extracts was investigated using the rhodamine 6G efflux assay and the propidium iodide-based membrane damage assay. Toxicity of the extracts was evaluated using the haemolytic and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. RESULTS: The results showed that acetone, ethanol and dichlorometane: methanol extracts had the most potent antibacterial activities against Pseudomonas aeruginosa (ATCC 27853). All three extracts caused membrane disruption of P. aeruginosa as shown by nucleic acid leakage. All three extracts were unable to inhibit efflux pumps. CONCLUSION: The presence of antibacterial activities and low toxicity shown by the extracts indicates that the plant may be a source of effective antibacterial against some bacterial infections caused by P. aeruginosa. The disruption of membrane integrity is one possible mode of action of antibacterial activity of the potent extracts.


Assuntos
Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Triumfetta/química , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Eritrócitos/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Ovinos
16.
Life Sci ; 237: 116947, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605708

RESUMO

AIMS: Pseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide, which is frequently linked with clinical treatment difficulties. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity with the specific mechanism. We hypothesized that inhibition of P. aeruginosa with ibuprofen is involved in the quorum sensing (QS) systems. MAIN METHODS: CFU was utilized to assessed the growth condition of P. aeruginosa. Crystal violent staining and acridine orange staining was used to evaluate the biofilm formation and adherence activity. The detection of QS virulence factors such as pyocyanin, elastase, protease, and rhamnolipids were applied to investigation the anti-QS activity of ibuprofen against P. aeruginosa. The production of 3-oxo-C12-HSL and C4-HSL was confirmed by liquid chromatography/mass spectrometry analysis. qRT-PCR was used to identify the QS-related gene expression. Furthermore, we explored the binding effects between ibuprofen and QS-associated proteins with molecular docking. KEY FINDINGS: Ibuprofen inhibits P. aeruginosa biofilm formation and adherence activity. And the inhibitory effects of ibuprofen on C4-HSL levels were concentration-dependent (p < 0.05), while it has no effect on 3-oxo-C12-HSL. Moreover, ibuprofen attenuates the production of virulence factors in P. aeruginosa (p < 0.05). In addition, the genes of QS system were decreased after the ibuprofen treatment (p < 0.05). Of note, ibuprofen was binding with LuxR, LasR, LasI, and RhlR at high binding scores. SIGNIFICANCE: The antibiofilm and anti-QS activity of ibuprofen suggest that it can be a candidate drug for the treatment of clinical infections with P. aeruginosa.


Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Ibuprofeno/farmacologia , Pseudomonas aeruginosa/genética , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/genética , Anti-Inflamatórios não Esteroides/farmacologia , Biofilmes/efeitos dos fármacos , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento
17.
BMC Infect Dis ; 19(1): 853, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619192

RESUMO

BACKGROUND: Between January 2015 and July 2017, we investigated the frequency of carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Pseudomonas aeruginosa (CRPA) at the Mulago Hospital intensive care unit (ICU) in Kampala, Uganda. Carbapenemase production and carbapenemase gene carriage among CRAB and CRPA were determined; mobility potential of carbapenemase genes via horizontal gene transfer processes was also studied. METHODS: Clinical specimens from 9269 patients were processed for isolation of CRAB and CRPA. Drug susceptibility testing was performed with the disk diffusion method. Carriage of carbapenemase genes and class 1 integrons was determined by PCR. Conjugation experiments that involved blaVIM positive CRAB/CRPA (donors) and sodium azide resistant Escherichia coli J53 (recipient) were performed. RESULTS: The 9269 specimens processed yielded 1077 and 488 isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. Of these, 2.7% (29/1077) and 7.4% (36/488) were confirmed to be CRAB and CRPA respectively, but 46 were available for analysis (21 CRAB and 25 CRPA). Majority of specimens yielding CRAB and CRPA were from the ICU (78%) while 20 and 2% were from the ENT (Ear Nose & Throat) Department and the Burns Unit, respectively. Carbapenemase assays performed with the MHT assay showed that 40 and 33% of CRPA and CRAB isolates respectively, were carbapenemase producers. Also, 72 and 48% of CRPA and CRAB isolates respectively, were metallo-beta-lactamase producers. All the carbapenemase producing isolates were multidrug resistant but susceptible to colistin. blaVIM was the most prevalent carbapenemase gene, and it was detected in all CRAB and CRPA isolates while blaOXA-23 and blaOXA-24 were detected in 29 and 24% of CRAB isolates, respectively. Co-carriage of blaOXA-23 and blaOXA-24 occurred in 14% of CRAB isolates. Moreover, 63% of the study isolates carried class 1 integrons; of these 31% successfully transferred blaVIM to E. coli J53. CONCLUSIONS: CRAB and CRPA prevalence at the Mulago Hospital ICU is relatively low but carbapenemase genes especially blaVIM and blaOXA-23 are prevalent among them. This requires strengthening of infection control practices to curb selection and transmission of these strains in the hospital.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii , Infecção Hospitalar/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Resistência beta-Lactâmica , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Uganda , beta-Lactamases
19.
Rev Soc Bras Med Trop ; 52: e20190237, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508785

RESUMO

INTRODUCTION: The increased use of colistin against infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa has resulted in colistin resistance. The purpose of this study was to detect plasmid-mediated mcr-1 gene in colistin-resistant A. baumannii and P. aeruginosa isolates. METHODS: A total of 146 clinical isolates of A. baumannii (n = 62) and P. aeruginosa (n = 84) were collected from the four largest tertiary care hospitals in Peshawar, Pakistan. All bacterial isolates were phenotypically screened for multidrug resistance using the Kirby-Baur disc diffusion method. The minimum inhibitory concentration (MIC) of colistin in all isolates was phenotypically performed using dilution methods. mcr-1 gene was detected through polymerase chain reaction and the nucleotide sequence of amplicon was determined using Sanger sequencing. RESULTS: Approximately 96.7% A. baumannii and 83.3% P. aeruginosa isolates were resistant to multiple antibiotics. Colistin resistance was found in 9.6% (6/62) of A. baumannii and 11.9% (10/84) of P. aeruginosa isolates. Among 16 colistin resistant isolates, the mcr-1 gene was detected in one A. baumannii (1.61% of total isolates; 16.6% of colistin resistant isolates) and one P. aeruginosa strain (1.19% of total isolates; 10% of colistin resistant isolates). Nucleotide BLAST showed 98-99% sequence similarity to sequences of the mcr-1 gene in GenBank. CONCLUSIONS: Our study reports, for the first time, the emergence of plasmid-mediated mcr-1-encoded colistin resistance in multidrug resistant strains of A. baumannii and P. aeruginosa. Further large scales studies are recommended to investigate the prevalence of this mode of resistance in these highly pathogenic bacteria.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Paquistão , Plasmídeos/genética , Pseudomonas aeruginosa/efeitos dos fármacos
20.
J Med Microbiol ; 68(11): 1591-1595, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553303

RESUMO

Patient-derived isolates of the opportunistic pathogen Pseudomonas aeruginosa are frequently resistant to antibiotics due to the presence of sequence variants in resistance-associated genes. However, the frequency of antibiotic resistance and of resistance-associated sequence variants in environmental isolates of P. aeruginosa has not been well studied. Antimicrobial susceptibility testing (ciprofloxacin, ceftazidime, meropenem, tobramycin) of environmental (n=50) and cystic fibrosis (n=42) P. aeruginosa isolates was carried out. Following whole genome sequencing of all isolates, 25 resistance-associated genes were analysed for the presence of likely function-altering sequence variants. Environmental isolates were susceptible to all antibiotics with one exception, whereas patient-derived isolates had significant frequencies of resistance to each antibiotic and a greater number of likely resistance-associated genetic variants. These findings indicate that the natural environment does not act as a reservoir of antibiotic-resistant P. aeruginosa, supporting a model in which antibiotic susceptible environmental bacteria infect patients and develop resistance during infection.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Microbiologia Ambiental , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Ceftazidima/farmacologia , Ciprofloxacino/farmacologia , Fibrose Cística/microbiologia , Genômica , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Tobramicina/farmacologia
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