Further understanding of Pseudomonas aeruginosa’s ability to horizontally acquire virulence: possible intervention strategies

Abstract

Article highlightsA review of the state of the art of the fast-moving field of Pseudomonas aeruginosa genomics Insight into the species population structure that shows the genetic diversity underlying its evolutionary and environmental flexibility.Examination of high-risk multidrug resistant clone evolution and penetration into healthcare systems.Consideration of alternatives and possible adjuncts to antibiotic chemotherapy including environmental control of AMR isolates.Review possible interventions with potential to control or reduce the ability for P. aeruginosa to gain virulence via HGT. Expert OpinionAnalysis of the genome of Pseudomonas aeruginosa has greatly intensified in recent years following the publication of the type strain PAO1 genome sequence in 2000. Phenotypically diverse and a coloniser of a large variety of natural habitats, this species is able to infect both plants and humans using the same virulence armamentarium. The genomes of 4660 P. aeruginosa are in the public domain and these have started to reveal the reasons for the species evolutionary success. For a species with a relatively large genome of about 6.3 million nucleotides coding for an estimated 5600 genes the essential core genome appears surprisingly small -only 321 genes. The vast majority of P. aeruginosa genes are shared between a small number of isolates with approximately half found in only one isolate. This unusually high level of genetic diversity is driven by frequent horizontal gene transfer events between members of the species as well as extra-species associations that are evidenced by, for example the acquisition of antibiotic resistance genes on mobile genetic elements such as plasmids containing carbapenem resistance and even colistin resistance determinants.Perhaps thankfully in this species, although multiple drug resistance (MDR) is commonplace even in environmental isolates, extreme (XDR) and pan-drug resistances are much less common and largely restricted to a relatively small number of genetic backgrounds. These high-risk clones can be easily identified by genome sequencing and there is good potential for this to become routine so that rapid diagnostics can provide antibiotic sensitivity and even virulence potential data in a clinically useful timeframe that can minimise the untargeted, empirical use of that valuable resources -antibiotics.Genomic sequencing is now used to trace P. aeruginosa outbreaks retrospectively but technology is currently sufficiently advanced to allow real-time outbreak analyses in hospitals and other healthcare settings. Currently this is financially unviable in most settings but the near future promises declining costs for genomic sequencing and future innovations will reduce the human resource requirements of current epidemiological analyses.Pseudomonas aeruginosa exists almost exclusively in biofilms which provide challenges for therapeutic intervention due to the low metabolic activity of some cells, the inability of some antibiotics to adequately penetrate the biofilm matrix and th...

No Correlation between Biofilm Formation, Virulence Factors, and Antibiotic Resistance in Pseudomonas aeruginosa: Results from a Laboratory-Based In Vitro Study

“…These enzymes are often encoded by horizontally-transferable genes, which are often also associated with resistance determinants to other classes of antimicrobial drugs [60]. Currently, the propagation of carbapenemase-producing organisms, especially in non-fermenting Gram-negative bacteria, is a public health issue these resistance-determinants may rapidly disseminate, leading to outbreaks of bacteria with extensive resistance [61]. While Class A and D carbapenemases have also been described, the metallo-β-lactamases blaVIM and blaIMP are the most prevalent in Pseudomonas spp.…”

Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights

“…PGNBs are also a major challenge in public health, such as P. aeruginosa ( 97 ) and A. baumannii ( 98 ). P. aeruginosa is one of the main opportunistic pathogenic bacteria in hospitals ( 99 , 100 ), which often results in post-operative ( 101 ) or post-burn wound infections ( 102 ), bacteremia ( 103 ) and sepsis ( 104 ). Antimicrobial resistance also exists in P. aeruginosa , it has been discovered that melatonin has a direct suppressive role in carbapenem-resistant P. aeruginosa ( 54 ).…”

Development of a rapid method for assessing the efficacy of antibacterial photocatalytic coatings

“…Applications where they may be useful include hospital environments (Reid et al, 2018;Priyadarshini et al, 2020), decontamination and remediation of water (Ioannou-Ttofa et al, 2019;Oliveira et al, 2019;Redfern and Enright, 2020), highfrequency contact surfaces (Kim et al, 2018), and in air purification systems (Mohamed and Awad, 2020). However, the translation of these reports to real-world systems may be limited by several factors.…”

“…This is because the reactive oxygen species generated during photocatalysis cause the bacterial cells to exhibit a stress or SOS response. This coordinated response may upregulate certain genes that mediate efflux pumps, mutation rate, biofilm formation, and horizontal gene transfer -all of which are elements that may contribute to antibacterial resistance (Redfern and Enright, 2020;Yin et al, 2020). By including more exposure times, it can be ascertained that a candidate material exhibits rapid inactivation of microorganisms, in addition to longterm activity that may help prevent colonisation of the surface.…”

“…Surface contamination and subsequent biofilm formation has major implications in certain domains where the hygienic status of the environment is paramount. Industries such as food, beverage, pharmaceutical, biomedical and wastewater remediation all require that microbial populations (bacteria, fungi and viruses) are controlled to prevent the spread of infectious disease, limit horizontal gene transfer, avoid product spoilage, and reduce operating costs (Choi et al, 2007;Simões et al, 2010;Bruscolini et al, 2015;Priha et al, 2015;Redfern and Enright, 2020). Amongst a host of strategies aimed at controlling, reducing or preventing such contamination and colonisation, the application of photocatalytic thin film coatings to surfaces is one approach (Foster et al, 2011).…”