ExoS effector in Pseudomonas aeruginosa Hyperactive Type III secretion system mutant promotes enhanced Plasma Membrane Rupture in Neutrophils

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1013021 - e1013021

Published: April 2, 2025

Pseudomonas aeruginosa is an opportunistic pathogen responsible for airway infections in immunocompromised individuals, including those with cystic fibrosis (CF). P. has a type III secretion system (T3SS) that translocates effectors into host cells. ExoS T3SS effector ADP ribosyltransferase (ADPRT) activity. ADPRT activity promotes virulence by inhibiting phagocytosis and limiting oxidative burst neutrophils. The also flagellin, which can activate the NLRC4 inflammasome, resulting in: 1) gasdermin-D pores, release of IL-1β pyroptosis; 2) histone 3 citrullination (CitH3), nuclear DNA decondensation expansion neutrophil cytosol incomplete NET extrusion. However, studies PAO1 indicate inhibits inflammasome Here, we identified + CF clinical isolate hyperactive T3SS. Variants mutant or were used to infect neutrophils from C57BL/6 mice wildtype engineered have genotype defects assembly. Responses assembly assayed found be similar regulated extrusion responses, like PAO1, but promoted enhanced CitH3 plasma membrane rupture (PMR). Glycine supplementation inhibited PMR mutant, suggesting ninjurin-1 required this process. These results identify as pathogenic hypervirulent .

Language: Английский

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Adaptation and Evolution of Pathogens in the Cystic Fibrosis Lung

Journal of the Pediatric Infectious Diseases Society, Journal Year: 2022, Volume and Issue: 11(Supplement_2), P. S23 - S31

Published: Sept. 1, 2022

Abstract As opposed to acute respiratory infections, the persistent bacterial infections of lung that characterize cystic fibrosis (CF) provide ample time for bacteria evolve and adapt. The process adaptation is recorded in mutations accumulate over genomes infecting bacteria. Some these lead obvious phenotypic differences such as antibiotic resistance or well-known mucoid phenotype Pseudomonas aeruginosa. Other may be just important but harder detect increased mutation rates, cell surface changes, shifts metabolism nutrient acquisition. Remarkably, many adaptations occur again different patients, signaling are adapting solve specific challenges CF tract. This parallel evolution even extends across distinct species. review addresses systems known change long-term with a special emphasis on cross-species comparisons. Consideration given how impact health CF, possible evolutionary mechanisms repeated adaptations.

Language: Английский

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Staphylococcalsecreted cytotoxins are competition sensing signals forPseudomonas aeruginosa

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 29, 2023

ABSTRACT Coinfection with two notorious opportunistic pathogens, the Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus , dominates chronic pulmonary infections. While coinfection is associated poor patient outcomes, interspecies interactions responsible for such decline remain unknown. Here, we dissected molecular mechanisms of sensing between P. S. . We discovered that senses secreted peptides and, counterintuitively, moves towards these toxins. tolerates a strategy through “competition sensing”, whereby it preempts imminent danger/competition by arming cells type six secretion (T6S) iron acquisition systems. Intriguingly, while T6S predominantly described as weaponry targeting eukaryotic cells, find essential full competition previously undescribed role T6S. Importantly, was activated during bronchial epithelia, including islands human cells. This study reveals critical insight into both how antagonism may cause collateral damage to host environment.

Language: Английский

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Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(5)

Published: Sept. 12, 2022

Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard care guidelines for the management CF CRS suggest treatment airway may ameliorate lower disease. We sought to determine whether changes sinus microbial community diversity specific taxa known cause lung are associated increased inflammation. performed 16S rRNA gene sequencing, supplemented cytokine analyses, microscopy, bacterial culturing, on samples from sinuses 27 adults CRS. At each study visit, participants underwent endoscopic paranasal sampling clinical evaluation. identified key drivers composition evaluated relationships between outcomes Sinus was low, unstable, many exhibiting alternating dominance Pseudomonas aeruginosa staphylococci over time. Despite tendency by these two taxa, communities were highly individualized shifted during exacerbation symptoms. Exacerbations also dominated Staphylococcus spp. Reduced linked worse inflammatory status (including interleukin-1β [IL-1β]). Increased IL-1β appearance, other cytokines dynamics. Our work revealed previously unknown instability link inflammation, lack diversity,

Language: Английский

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SprayNPray: user-friendly taxonomic profiling of genome and metagenome contigs

BMC Genomics, Journal Year: 2022, Volume and Issue: 23(1)

Published: March 12, 2022

Abstract Background Shotgun sequencing of cultured microbial isolates/individual eukaryotes (whole-genome sequencing) and communities (metagenomics) has become commonplace in biology. Very often, sequenced samples encompass organisms spanning multiple domains life, necessitating increasingly elaborate software for accurate taxonomic classification assembled sequences. Results While many tools exist, SprayNPray offers a quick user-friendly, semi-automated approach, allowing users to separate contigs by taxonomy (and other metrics) interest. Easy installation, usage, intuitive output, which is amenable visual inspection and/or further computational parsing, will reduce barriers biologists beginning analyze genomes metagenomes. This approach can be used broad-level overviews, preliminary analyses, or as supplement binning software. profiles using metrics, including closest homologs from user-specified reference database, gene density, read coverage, GC content, tetranucleotide frequency, codon-usage bias. Conclusions The output this designed allow spot-check metagenome-assembled genomes, identify, remove putative contaminants isolate assemblies, identify bacteria eukaryotic assemblies vice-versa), possible horizontal transfer events.

Language: Английский

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Lytic bacteriophages interact with respiratory epithelial cells and induce the secretion of antiviral and proinflammatory cytokines

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

ABSTRACT Phage therapy is a therapeutic approach to treat multidrug resistant infections that employs lytic bacteriophages (phages) eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there scarce data regarding effects on human host. Here, we aimed understand how phages interact with cells of airway epithelium, tissue site colonized by bacterial biofilms numerous chronic respiratory disorders. We determined interactions between and epithelial depend specific phage properties well physiochemical features microenvironment. Although poor at internalizing phages, epithelium responds exposure changing transcriptional profile secreting antiviral proinflammatory cytokines correlate families. Overall, our findings indicate mammalian responses are heterogenous could potentially alter way local defenses aid clearance during therapy. Thus, besides receptor specificity particular isolate, criteria select should be expanded include cell responses.

Language: Английский

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Co-occurring microflora and mucin drive Pseudomonas aeruginosa diversification and pathoadaptation

ISME Communications, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 1, 2024

Abstract While several environmental factors contribute to the evolutionary diversification of pathogenic bacterium Pseudomonas aeruginosa during cystic fibrosis lung infections, relatively little is known about impact surrounding microbiota. By using in vitro experimental evolution, we show that presence Stenotrophomonas maltophilia, Staphylococcus aureus, or them both, prevent evolution loss virulence, which repeatedly occurs absence these species due mutations regulators Quinolone Signal quorum sensing system, vqsM and pqsR. Moreover, strength effect co-occurring attenuated through changes physical environment by addition mucin, resulting selection for phenotypes resembling those evolved species. Together, our findings variation mucosal polymicrobial can determine trajectory P. aeruginosa, partly explaining its pathoadaptation from acute chronic phenotype infections.

Language: Английский

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Genomic stasis over millions of years in subseafloor sediment

Environmental Microbiology, Journal Year: 2024, Volume and Issue: 26(8)

Published: July 1, 2024

Abstract One of the significant challenges in microbiology is to understand extent and mechanisms evolution within life beneath surface Earth. The population bottleneck that microbes deep marine sediment experience implies mutational genetic forces could lead higher levels relaxed selection an increase pseudogenes. To investigate this hypothesis, a group Thalassospira strains were isolated from subseafloor 3 6 million years old, as reported by Orsi colleagues 2021. These isolates, representing lineages have been buried for millions years, offer excellent opportunity study seafloor over long period. existence closely related environments on Earth enabled us examine impact each group. We discovered isolates show lineage‐specific similarities world, both overall intensity genome specific genes affected mutation. found no signs increased or other notable genomic changes genomes seafloor, suggesting these awakened million‐year near‐stasis. unique characteristics lineage must then reflect surface‐inhabiting decendants acquired past 3–6 years. Remarkably, appear stably maintained their midst metabolic dormancy extremely generation times.

Language: Английский

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Definition of sinonasal and otological exacerbation in patients with primary ciliary dyskinesia: an expert consensus

ERJ Open Research, Journal Year: 2024, Volume and Issue: 10(6), P. 00218 - 2024

Published: Aug. 22, 2024

Background Recurrent infections of the nose, sinuses and ears are common problems for people with primary ciliary dyskinesia. While pulmonary exacerbations in dyskinesia defined, there is no definition ear-nose-throat exacerbations, a potential outcome research clinical trials. Methods We set up an expert panel 24 specialists, respiratory physicians, other healthcare professionals patients to develop consensus definitions sinonasal otological children adults settings. reviewed literature used modified Delphi approach four electronic surveys. Results Definitions both based on combination major minor criteria, requiring three or two at least criteria each. Major exacerbation 1) reported acute increase nasal discharge change colour, 2) pain sensitivity sinus regions 3) mucopurulent examination. Minor include symptoms, examination signs, doctor's decision treat improvement after 14 days. ear sensitivity, discharge, 4) signs otitis media otoscopy. hearing problems, complication, treat. Conclusion These might offer useful measure different They should be validated future studies trials together outcomes, assess their usability.

Language: Английский

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Phenotypic and genotypic characteristics of Pseudomonas aeruginosa isolated from cystic fibrosis patients with chronic infections

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 20, 2023

Patients with cystic fibrosis are predisposed to chronic respiratory tract infections caused by Pseudomonas aeruginosa. As the disease progresses, microorganism diversifies into genotypically and phenotypically different strains which may coexist in patient's airways for years. Adaptation of patients probably occurs response host's airway environment, elements immune system antibiotic therapy. Due persistence airways, a comprehensive molecular analysis was conducted. The included 120 isolated from 10 adult P. aeruginosa infection. aim study analyze patterns trace their transmission population patients, as well relationship specific phenotypic features. In research, genotypic performed using pulsed-field gel electrophoresis. results number features were added outcomes studies. result, 28 genotypes distinguished. also showed cross-transmission between patients. 3 transmissible clusters identified, including IG1 IG2 9 each, obtained 2 IG3 cluster 6 Moreover, it found that some several unrelated transiently or permanently infect tract. A understanding adaptation help develop more effective antimicrobial therapies identify new targets future drugs order prevent progression infection stages.

Language: Английский

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