Hypermutator Pseudomonas aeruginosa exploits multiple genetic pathways to develop multidrug resistance during long-term infections in the airways of cystic fibrosis patients.

Hypermutator Pseudomonas aeruginosa exploits multiple genetic pathways to develop multidrug resistance during long-term infections in the airways of cystic fibrosis patients. Antimicrob Agents Chemother. 2020 Feb 18;: Authors: Colque CA, Albarracín Orio AG, Feliziani S, Marvig RL, Tobares AR, Johansen HK, Molin S, Smania AM Abstract Pseudomonas aeruginosa exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in P. aeruginosa isolated from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic CF infections. However, the within-patient genetic diversity of P. aeruginosa populations related to antibiotic resistance remains unexplored. Here, we show the evolution of the mutational resistome profile of a P. aeruginosa hypermutator lineage by performing longitudinal and transversal analyses of isolates collected from a CF patient throughout 20 years of chronic infection. Our results show the accumulation of thousands of mutations with an overall evolutionary history characterized by purifying selection. However, mutations in antibiotic resistance genes appear to be positively selected, driven by antibiotic treatment. Antibiotic resistance increased as infection progressed towards the establishment of a population constituted by genotypically diversified coexisting sub-lineages, all of which converged to multi-drug...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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Abstract Achromobacter is a genus of non-fermenting Gram negative bacteria under order Burkholderiales Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g. most cephalosporins, aztreonam and aminoglycosides), and are increasingly acquiring resistance ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In this study, the full-length PcrV was divided into four domains with the guidance of its structure, and the Nter domain (Met1-Lys127) and H12 domain (Leu251-Ile294) were found to be immunodominant. Subsequently, Nter and H12 were combined with a flexible linker to generate an artificial PcrV derivative (PcrVNH). PcrVNH was successfully produced in E. coli and behaved as a homogenous monomer. Moreover, immunization with PcrVNH elicited a multifactorial immune response and conferred broad protection in an acute PA pneumonia model and was equally effective to full-length PcrV. In addition, passive immunization with anti-Pcr...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionEvaluation of hypersusceptible mutants identified the association betweenlptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.
Source: MicrobiologyOpen - Category: Microbiology Authors: Tags: SPECIAL ISSUE: ANTIMICROBIAL RESISTANCE Source Type: research
Raquel Ferrer-Espada1,2, Xiaojing Liu1,2, Xueping Sharon Goh1,2 and Tianhong Dai1,2* 1Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States 2Vaccine &Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Polymicrobial biofilms, in which mixed microbial species are present, play a significant role in persistent infections. Furthermore, polymicrobial biofilms promote antibiotic resistance by allowing interspecies transfer of antibiotic resistance genes. In the present study, we investigated the effec...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Mycobacterium abscessus (MAB) is an emerging pathogen, particularly for individuals with cystic fibrosis (CF) and has become the most lethal and frequent multidrug-resistant mycobacterial infection in the developed World. MAB infections are increasingly common in CF cohorts, and are difficult and sometimes impossible to treat. Very little is known about the genetic determinants controlling MAB infection, virulence, and antimicrobial resistance, or how mycobacterial and non-mycobacterial genes (derived from horizontal gene transfer) interact to influence pathophysiology. We therefore sought to define the critical pathways r...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
ConclusionC/T showed excellent in vitro activity against P. aeruginosa CF clinical isolates. This antimicrobial agent is a potential therapeutic option when presented with challenging MDR P. aeruginosa and S. maltophilia exacerbations. Further clinical experience and trials in CF are required to determine the place of C/T in clinical practice.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
In this study ceftolozane/tazobactam was compared to other commonly used intravenous antibiotics against 193 non-fermenting Gram-negative bacteria isolated from CF sputum specimens, including P. aeruginosa, Achromobacter xylosoxidans, Stenotrophomonas maltophilia and Burkholderia. MICs to ceftolozane/tazobactam were determined by standard E-test assay and interpreted according to current EUCAST guidelines. RESULTS Ceftolozane/tazobactam had good in vitro antimicrobial activity against CF clinical isolates of P. aeruginosa in comparison to other antimicrobials with the exception of colistin. Ceftolozane/tazobactam also had ...
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Therapies for multidrug resistant and extensively drug-resistant non-fermenting gram-negative bacteria causing nosocomial infections: a perilous journey toward "molecularly targeted" therapy. Expert Rev Anti Infect Ther. 2018 Jan 09;: Authors: El Chakhtoura NG, Saade E, Iovleva A, Yasmin M, Wilson B, Perez F, Bonomo RA Abstract INTRODUCTION: Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of "serious" by the Centers for Disease C...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
te;nez-Martínez L, Arcos SC, Navas A, Oliver A Abstract The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa is frequently linked to widespread international strains designated as high-risk clones. In this work we attempted to decipher the interplay between resistance profiles, high-risk clones and virulence, testing a large (n=140) collection of well characterized P. aeruginosa isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis and environment) in a Caenorhabditis elega...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In this study, we report the draft genome sequence of a multidrug-resistant P. aeruginosa strain belonging to sequence type ST235, isolated from the respiratory tract of a CF patient with chronic colonisation. Whole-genome sequencing analysis revealed a 6.7 Mb genome size and the presence of 12 antibiotic resistance genes, including the rmtG gene conferring high-level aminoglycoside resistance, located on the chromosome.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
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