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

Abstract

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

Relationship between Biofilm-Formation, Phenotypic Virulence Factors and Antibiotic Resistance in Environmental Pseudomonas aeruginosa

“…Overall mortality associated with these infections may be as high as 20-60%, which is further compounded by the increasing levels of MDR in PA [56]. The hallmarks of PA's pathogenicity include its cell-mediated (endotoxin, flagella, pili, and adhesins) and secreted virulence determinants (type I-III secretion systems, degrading enzymes, and exotoxins) [2,57]. Biofilm may be considered another critical secreted virulence factor, which allows for the survival of their host; biofilms have a complex composition including aggregated bacteria, carbohydrates (among them, exopolysaccharides are the most important), DNA, lipids, proteins, and ions, which all have a role in binding water to this matrix [58,59].…”

Virulence genes contributing to Aeromonas veronii pathogenicity in Nile tilapia (Oreochromis niloticus): approaching the development of live and inactivated vaccines

“…Previous research shows that many number of interconnected factors cause the pathogenicity of Aeromonas . There are confirmed virulence factors, such as outer membrane proteins, toxins, proteases, motility-related factors, secretion systems, quorum, and iron ion acquisition systems, as well as hemolytic and cytotoxic activities (Qin et al 2022 ). Pathogenicity was related to the presence of virulence genes in Aeromonas strains, which play an essential role in disease development (Hossain et al 2018 ; Sun et al 2016 ; Zhang et al 2019 ).…”

Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection

“…( Gross et al, 2008 ; Brickman and Armstrong, 2018 ). Both have evolved from environmental origins ( Mathee et al, 2008 ), and both have evolved a variety of virulence mechanisms that allows them to be adaptable to different environmental stressors, including host immune responses ( Hauser, 2011 ; Gestal et al, 2019a , b ; Qin et al, 2022 ). B. pertussis is the causative agent of whooping cough, also known as pertussis disease or the 100-day cough ( Kilgore et al, 2016 ).…”