Impact of multidrug resistance on the virulence and fitness of Pseudomonas aeruginosa: a microbiological and clinical perspective.

Pseudomonas aeruginosa is one of the most common nosocomial pathogens and part of the top emergent species associated with antimicrobial resistance that has become one of the greatest threat to public health in the twenty-first century. This bacterium is provided with a wide set of virulence factors that contribute to pathogenesis in acute and chronic infections. This review aims to summarize the impact of multidrug resistance on the virulence and fitness of P.

Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteraemic urinary tract infections: a post-hoc analysis of a multicentre prospective cohort in Spain.

Background: The global burden associated with antimicrobial resistance is of increasing concern.

Aim: To evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated bacteraemic urinary tract infections (BUTIs).

Methods: This was a prospective, multicentre, post-hoc analysis of patients with healthcare-associated-BUTI (ITUBRAS-2).

Evolution repeats itself in replicate long-term studies in the wild.

The extent to which evolution is repeatable remains debated. Here, we study changes over time in the frequency of cryptic color-pattern morphs in 10 replicate long-term field studies of a stick insect, each spanning at least a decade (across 30 years of total data). We find predictable "up-and-down" fluctuations in stripe frequency in all populations, representing repeatable evolutionary dynamics based on standing genetic variation.

Transferable AmpCs in : interplay with peptidoglycan recycling, mechanisms of hyperproduction, and virulence implications.

Chromosomal and transferable AmpC β-lactamases represent top resistance mechanisms in different gram-negatives, but knowledge regarding the latter, mostly concerning regulation and virulence-related implications, is far from being complete. To fill this gap, we used (KP) and two different plasmid-encoded AmpCs [DHA-1 (AmpR regulator linked, inducible) and CMY-2 (constitutive)] as models to perform a study in which we show that blockade of peptidoglycan recycling through AmpG permease inactivation abolished DHA-1 inducibility but did not affect CMY-2 production and neither did it alter KP pathogenic behavior. Moreover, whereas regular production of both AmpC-type enzymes did not attenuate KP virulence, when DHA-1 was expressed in an -defective mutant, killing was significantly (but not drastically) attenuated.

Genetic variation within a stick-insect species associated with community-level traits.

Phenotypic variation within species can affect the ecological dynamics of populations and communities. Characterizing the genetic variation underlying such effects can help parse the roles of genetic evolution and plasticity in "eco-evolutionary dynamics" and inform how genetic variation may shape patterns of evolution. Here, we employ genome-wide association (GWA) methods in Timema cristinae stick insects and their co-occurring arthropod communities to identify genetic variation associated with community-level traits.

The balance between antibiotic resistance and fitness/virulence in : an update on basic knowledge and fundamental research.

The interplay between antibiotic resistance and bacterial fitness/virulence has attracted the interest of researchers for decades because of its therapeutic implications, since it is classically assumed that resistance usually entails certain biological costs. Reviews on this topic revise the published data from a general point of view, including studies based on clinical strains or -evolved mutants in which the resistance phenotype is seen as a final outcome, i.e.

antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis.

Background: healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of over a five-year time lapse.

Methods: A total of 3.

A stabilizing eco-evolutionary feedback loop in the wild.

There is increasing evidence that evolutionary and ecological processes can operate on the same timescale (i.e., contemporary time).

Role of Enzymatic Activity in the Biological Cost Associated with the Production of AmpC β-Lactamases in Pseudomonas aeruginosa.

In the current scenario of growing antibiotic resistance, understanding the interplay between resistance mechanisms and biological costs is crucial for designing therapeutic strategies. In this regard, intrinsic AmpC β-lactamase hyperproduction is probably the most important resistance mechanism of Pseudomonas aeruginosa, proven to entail important biological burdens that attenuate virulence mostly under peptidoglycan recycling alterations. P.

Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial.

Objectives: To determine the susceptibility profiles and the resistome of Pseudomonas aeruginosa isolates from European ICUs during a prospective cohort study (ASPIRE-ICU).

Methods: 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs of 12 antibiotics were determined by broth microdilution.

Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Bloodstream Infections.

is a major cause of nosocomial bloodstream infections. This microorganism secretes two major proteases, alkaline protease A (AprA) and elastase B (LasB). Despite several studies having demonstrated that both purified proteases cleave a number of components of the immune system, their contribution to bloodstream infections remains poorly investigated.

Comparative analysis of in vitro dynamics and mechanisms of ceftolozane/tazobactam and imipenem/relebactam resistance development in Pseudomonas aeruginosa XDR high-risk clones.

Objectives: To analyse the dynamics and mechanisms of stepwise resistance development to ceftolozane/tazobactam and imipenem/relebactam in XDR Pseudomonas aeruginosa clinical strains.

Methods: XDR clinical isolates belonging to ST111 (main resistance mechanisms: oprD-, dacB-, CARB-2), ST175 (oprD-, ampR-G154R) and ST235 (oprD-, OXA-2) high-risk clones were incubated for 24 h in Müeller-Hinton Broth with 0.125-64 mg/L of ceftolozane + tazobactam 4 mg/L or imipenem + relebactam 4 mg/L.

In vitro evolution of cefepime/zidebactam (WCK 5222) resistance in Pseudomonas aeruginosa: dynamics, mechanisms, fitness trade-off and impact on in vivo efficacy.

Objectives: To study the dynamics, mechanisms and fitness cost of resistance selection to cefepime, zidebactam and cefepime/zidebactam in Pseudomonas aeruginosa.

Methods: WT P. aeruginosa PAO1 and its ΔmutS derivative (PAOMS) were exposed to stepwise increasing concentrations of cefepime, zidebactam and cefepime/zidebactam.

Validation of MALDI-TOF for the early detection of the ST175 high-risk clone of Pseudomonas aeruginosa in clinical isolates belonging to a Spanish nationwide multicenter study.

Introduction: Pseudomonas aeruginosa causes severe infections, particularly in healthcare settings and immunocompromised patients in whom MDR and XDR isolates are more prevalent. The aim of this study is to validate a method based on MALDI-TOF spectra analysis for early detection of the ST175 high-risk clone (HRC).

Methods: The MALDI-TOF spectra of the first 10 P.

Metagenomics Analysis Reveals an Extraordinary Inner Bacterial Diversity in Anisakids (Nematoda: Anisakidae) L3 Larvae.

L3 larvae of anisakid nematodes are an important problem for the fisheries industry and pose a potential risk for human health by acting as infectious agents causing allergies and as potential vectors of pathogens and microrganisms. In spite of the close bacteria-nematode relationship very little is known of the anisakids microbiota. Fresh fish could be contaminated by bacteria vectored in the cuticle or in the intestine of anisakids when the L3 larvae migrate through the muscles.

Rituximab for Inflammatory Myopathies in a Colombian Cohort.

Introduction/objectives: Rituximab (RTX) is a treatment for refractory inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). This study describes the characteristics of patients receiving RTX for myositis in our institution to evaluate its efficacy.

Method: We collected demographic data from all patients diagnosed with DM or PM who received RTX between 2011 and 2018.

A Genome-Based Model to Predict the Virulence of Pseudomonas aeruginosa Isolates.

Variation in the genome of , an important pathogen, can have dramatic impacts on the bacterium's ability to cause disease. We therefore asked whether it was possible to predict the virulence of isolates based on their genomic content. We applied a machine learning approach to a genetically and phenotypically diverse collection of 115 clinical isolates using genomic information and corresponding virulence phenotypes in a mouse model of bacteremia.

In vitro dynamics and mechanisms of resistance development to imipenem and imipenem/relebactam in Pseudomonas aeruginosa.

Objectives: We analysed the dynamics and mechanisms of resistance development to imipenem alone or combined with relebactam in Pseudomonas aeruginosa WT (PAO1) and mutator (PAOMS; ΔmutS) strains.

Methods: PAO1 or PAOMS strains were incubated for 24 h in Mueller-Hinton Broth with 0.125-64 mg/L of imipenem ± relebactam 4 mg/L.

Pathogenic characteristics of Pseudomonas aeruginosa bacteraemia isolates in a high-endemicity setting for ST175 and ST235 high-risk clones.

Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical concern. The interplay between antimicrobial resistance and virulence of P. aeruginosa was investigated in in vitro and in vivo studies.

Activity of Imipenem-Relebactam against a Large Collection of Pseudomonas aeruginosa Clinical Isolates and Isogenic β-Lactam-Resistant Mutants.

Imipenem and imipenem-relebactam MICs were determined for 1,445 clinical isolates and a large panel of isogenic mutants showing the most relevant mutation-driven β-lactam resistance mechanisms. Imipenem-relebactam showed the highest susceptibility rate (97.3%), followed by colistin and ceftolozane-tazobactam (both 94.

Association between Pseudomonas aeruginosa O-antigen serotypes, resistance profiles and high-risk clones: results from a Spanish nationwide survey.

Objectives: To evaluate the correlation of O-antigen serotypes with resistance profiles and high-risk clones in a Spanish nationwide survey.

Methods: Up to 30 consecutive healthcare-associated Pseudomonas aeruginosa isolates were collected during October 2017 from each of 51 hospitals (covering all Spanish regions) with a total of 1445 isolates studied. MICs of 13 antipseudomonal agents and MDR/XDR profiles had been previously determined, as well as whole-genome sequences of 185 representative XDR isolates.

In Vivo Validation of Peptidoglycan Recycling as a Target to Disable AmpC-Mediated Resistance and Reduce Virulence Enhancing the Cell-Wall-Targeting Immunity.

Background: Searching for new strategies to defeat Pseudomonas aeruginosa is of paramount importance. Previous works in vitro showed that peptidoglycan recycling blockade disables AmpC-dependent resistance and enhances susceptibility against cell-wall-targeting immunity. Our objective was to validate these findings in murine models.

Weighting the impact of virulence on the outcome of Pseudomonas aeruginosa bloodstream infections.

Objectives: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections.

Methods: A total of 593 P.