Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 25, 2022

Abstract Pseudomonas aeruginosa ( P. ) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infection requiring ventilation, such as COVID-19. also widely-used model bacterium for all biological areas. In addition to continued, intense efforts in understanding bacterial pathogenesis of including virulence factors (LPS, quorum sensing, two-component systems, 6 type secretion outer membrane vesicles (OMVs), CRISPR-Cas their regulation), rapid progress has been made further studying host-pathogen interaction, particularly host immune networks involving autophagy, inflammasome, non-coding RNAs, cGAS, etc . Furthermore, numerous technologic advances, bioinformatics, metabolomics, scRNA-seq, nanoparticles, drug screening, phage therapy, have used improve our defense. Nevertheless, much remains be uncovered about interactions between responses, mechanisms resistance by known or unannotated well mammalian cell signaling pathways. The widespread use antibiotics the slow development effective antimicrobials present daunting challenges necessitate new theoretical practical platforms screen develop mechanism-tested novel drugs treat intractable infections, especially those caused multi-drug strains. Benefited from advancing research tools technology, dissecting this pathogen’s feature entered into molecular mechanistic details dynamic holistic views. Herein, we comprehensively review discuss current status biophysical traits, behaviors, factors, invasive regulators, defense patterns against its infection, which point out directions future investigation add design and/or alternative therapeutics combat clinically significant pathogen.

Language: Английский

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Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Microorganisms, Journal Year: 2022, Volume and Issue: 10(6), P. 1239 - 1239

Published: June 16, 2022

Chronic and recurrent bacterial infections are frequently associated with the formation of biofilms on biotic or abiotic materials that composed mono- multi-species cultures bacteria/fungi embedded in an extracellular matrix produced by microorganisms. Biofilm is, among others, regulated quorum sensing (QS) which is interbacterial communication system usually two-component systems (TCSs) secreted autoinducer compounds activate signal transduction pathways through interaction their respective receptors. Embedded biofilms, bacteria protected from environmental stress stimuli, they often show reduced responses to antibiotics, making it difficult eradicate infection. Besides penetration antibiotics intricate structure sessile biofilm-embedded metabolic activity them intrinsically less sensitive antibiotics. Moreover, express elevated levels efflux pumps extrude thereby reducing intracellular levels. Some involved secretion QS biofilm-related materials, besides being important for removing toxic substances bacteria. pump inhibitors (EPIs) have been shown both prevent biofilm sensitize suggesting a relationship between these processes. Additionally, quenchers may affect antibiotic susceptibility. Thus, targeting elements regulate might be promising approach combat antibiotic-resistant infections.

Language: Английский

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Microbiome and metabolome features in inflammatory bowel disease via multi-omics integration analyses across cohorts

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 6, 2023

Abstract The perturbations of the gut microbiota and metabolites are closely associated with progression inflammatory bowel disease (IBD). However, inconsistent findings across studies impede a comprehensive understanding their roles in IBD potential as reliable diagnostic biomarkers. To address this challenge, here we comprehensively analyze 9 metagenomic 4 metabolomics cohorts from different populations. Through cross-cohort integrative analysis (CCIA), identify consistent characteristic commensal microbiota. Especially, three bacteria, namely Asaccharobacter celatus , Gemmiger formicilis Erysipelatoclostridium ramosum which rarely reported IBD. Metagenomic functional reveals that essential gene Two-component system pathway, linked to fecal calprotectin, implicated Metabolomics shows 36 identified significant differences, while these still unknown. further elucidate relationship between metabolites, construct multi-omics biological correlation (MOBC) maps, highlights microbial biotransformation deficiencies alterations aminoacyl-tRNA synthetases. Finally, biomarkers for diagnosis, validated multiple global (AUROC values ranging 0.92 0.98). Our results offer valuable insights resource developing mechanistic hypotheses on host-microbiome interactions

Language: Английский

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Using next generation antimicrobials to target the mechanisms of infection

npj Antimicrobials and Resistance, Journal Year: 2023, Volume and Issue: 1(1)

Published: Sept. 22, 2023

Abstract The remarkable impact of antibiotics on human health is being eroded at an alarming rate by the emergence multidrug resistant pathogens. There a recognised consensus that new strategies to tackle infection are urgently needed limit devasting antibiotic resistance our global healthcare infrastructure. Next generation antimicrobials (NGAs) compounds target bacterial virulence factors disrupt pathogenic potential without impacting viability. By disabling key required establish and maintain infection, NGAs make pathogens more vulnerable clearance immune system can potentially render them susceptible traditional antibiotics. In this review, we discuss developing field how advancements in area could offer viable standalone alternative or effective means prolong efficacy when used combination.

Language: Английский

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Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 19, 2023

Pseudomonas aeruginosa is one of the most important foodborne pathogens that can persist in leafy green vegetables and subsequently produce biofilms. In this study, synergistic effect thymoquinone nisin reducing biofilm formation P. on lettuce was evaluated, their anti-virulence anti-biofilm mechanisms were also investigated. At concentrations ranging from 0.5 to 2 mg/ml, inhibited production autoinducers virulence factors, enhanced susceptibility biofilms as evidenced by scanning electron microscopy confocal laser microscopy. Integrated transcriptomics, metabolomics, docking analyses indicated treatment disrupted quorum sensing (QS) system, altered cell membrane component, down-regulated expressions genes related virulence, efflux pump, antioxidation. The changed component repressed pump system permeability facilitated entrance into cells, thus improving nisin. dysfunctional QS antioxidant enzymes lead enhancement oxidative stress. stress energy metabolism protein ultimately attenuated pathogenicity PAO1. Our study has potential function a QS-based agent defend against combination with

Language: Английский

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Physiological responses and molecular mechanisms of biofilm formation induced by extracellular metabolites of euglena in Pseudomonas aeruginosa LNR1 for diesel biodegradation based on transcriptomic and proteomic

Environmental Research, Journal Year: 2024, Volume and Issue: 248, P. 118273 - 118273

Published: Jan. 25, 2024

Language: Английский

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Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 12, 2024

Abstract Purines and their derivatives control intracellular energy homeostasis nucleotide synthesis, act as signaling molecules. Here, we combine structural sequence information to define a purine-binding motif that is present in sensor domains of thousands bacterial receptors modulate motility, gene expression, metabolism, second-messenger turnover. Microcalorimetric titrations selected validate ability specifically bind purine derivatives, evolutionary analyses indicate sensors share common ancestor with amino-acid receptors. Furthermore, provide experimental evidence physiological relevance sensing system modulates c-di-GMP levels.

Language: Английский

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Whole-Genome Sequencing of Resistance, Virulence and Regulation Genes in Extremely Resistant Strains of Pseudomonas aeruginosa

Medical Sciences, Journal Year: 2025, Volume and Issue: 13(1), P. 6 - 6

Published: Jan. 3, 2025

Pseudomonas aeruginosa is a clinically significant opportunistic pathogen, renowned for its ability to acquire and develop diverse mechanisms of antibiotic resistance. This study examines the resistance, virulence, regulatory in extensively drug-resistant clinical strains P. aeruginosa. Antibiotic susceptibility was assessed using Minimum Inhibitory Concentration (MIC) method, whole-genome sequencing (WGS) performed on Illumina NovaSeq platform. The analysis demonstrated higher prevalence virulence genes compared resistance genes. Key factors identified included secretion systems, motility, adhesion, biofilm formation. Resistance observed comprised efflux pumps beta-lactamases, while systems involved two-component transcriptional regulators, sigma factors. Additionally, phenotypic profiles were found correlate with through genotypic analysis. underscores analyzed, highlighting urgent need alternative strategies address infections caused by bacteria.

Language: Английский

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Antibacterial activity and multi-target mechanism of harmane against Escherichia coli O157:H7 and its application on ready-to-eat leafy greens

International Journal of Food Microbiology, Journal Year: 2025, Volume and Issue: 431, P. 111084 - 111084

Published: Jan. 23, 2025

Language: Английский

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Epidemiology, Molecular Characteristics, and Virulence Factors of Carbapenem-Resistant Pseudomonas aeruginosa Isolated from Patients with Urinary Tract Infections

Infection and Drug Resistance, Journal Year: 2022, Volume and Issue: Volume 15, P. 141 - 151

Published: Jan. 1, 2022

Pseudomonas aeruginosa is an important pathogen that causes urinary tract infections. Carbapenems are the drugs of choice for treatment P. However, emergence and spread carbapenem-resistant (CRPA) a serious global health threat. In this study, we investigated epidemiology, molecular characteristics, drug resistance, virulence factors CRPA isolated from urine samples.A total 124 isolates were obtained samples collected between March 2020 February 2021. Clonal relatedness was evaluated using multilocus sequence typing (MLST) pulsed-field gel electrophoresis (PFGE). We performed antimicrobial susceptibility tests presence carbapenemase genes in isolates.The carbapenem resistance rate 46.7% (59/124). A 54 (91.5%) out 59 identified as multidrug-resistant. The majority (81.4%, 48/59) harbored genes, such blaIMP-6 or blaNDM-1. epidemiological analysis MLST, 88.1% confirmed to be ST773 (50.8%, 30/59) ST235 (37.3%, 22/59). harboring blaNDM-1 belonged (PFGE pulsotypes E1-E18, F) H1-H2, I1-I16) subtypes, respectively. studied simultaneously 10 14 16 examined. Nine factor (toxA, exoT, plcH, plcN, phzM, phzS, lasB, aprA, algD) all isolates.Our study shows blaNDM-1-known internationally high-risk clones with multiple factors-are widely area. These findings suggest continuous monitoring necessary prevent further carbapenemase-producing CRPA.

Language: Английский

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