Invasion and diversity in Pseudomonas aeruginosa urinary tract infections

Abstract

Introduction. P. aeruginosa is an opportunistic Gram-negative pathogen frequently isolated in urinary tract infections (UTI) affecting elderly and catheterized patients and associated with ineffective antibiotic treatment and poor clinical outcomes. Gap statement. Invasion has been shown to play an important role in UTI caused by E. coli but has only recently been studied with P. aeruginosa . The ability of P. aeruginosa to adapt and evolve in chronic lung infections is associated with resistance to antibiotics but has rarely been studied in P. aeruginosa UTI populations. Aim. We sought to determine whether phenotypic and genotypic heterogeneity exists in P. aeruginosa UTI isolates and whether, like urinary pathogenic Escherichia coli , these could invade human bladder epithelial cells – two factors that could complicate antibiotic treatment. Methodology. P. aeruginosa UTI samples were obtained from five elderly patients at the Royal Liverpool University Hospital as part of routine diagnostics. Fourty isolates from each patient sample were screened for a range of phenotypes. The most phenotypically diverse isolates were genome sequenced. Gentamicin protection assays and confocal microscopy were used to determine capacity to invade bladder epithelial cells. Results. Despite significant within-patient phenotypic differences, no UTI patient was colonized by distinct strains of P. aeruginosa . Limited genotypic differences were identified in the form of non-synonymous SNPs. Gentamicin protection assays and confocal microscopy provided evidence of P. aeruginosa ’s ability to invade bladder epithelial cells. Conclusions. Phenotypic variation and cell invasion could further complicate antibiotic treatment in some patients. More work is needed to better understand P. aeruginosa UTI pathogenesis and develop more effective treatment strategies.

Pseudomonas aeruginosa clinical blood isolates display significant phenotypic variability

“…aeruginosa virulence factors implicating pyocyanin production, biofilm production, and twitching motility as important mediators of pathogenesis [ 4 – 6 , 40 – 45 ]. We observed high variability amongst the phenotypes we assayed, which is consistent with other studied that found high variability amongst isolates from other clinical sites such as urinary tracts and cystic fibrosis lungs [ 22 – 24 ]. It is possible that none of the three specific phenotypes we assayed are important for blood infections or are only induced in blood-like environments.…”

“…If strains act as niche specialists there should be little variability amongst a suite of virulence factors than can be assayed in the lab. Alternatively, clinical and environmental isolates can have genomic similarity while displaying phenotypic heterogeneity [ 22 – 24 ].…”

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“…There have been many studies on P. aeruginosa virulence factors implicating pyocyanin production, biofilm production, and twitching motility as important mediators of pathogenesis [4][5][6][40][41][42][43][44][45]. We observed high variability amongst the phenotypes we assayed, which is consistent with other studied that found high variability amongst isolates from other clinical sites such as urinary tracts and cystic fibrosis lungs [22][23][24]. It is possible that none of the three specific phenotypes we assayed are important for blood infections or are only induced in blood-like environments.…”

“…If strains act as niche specialists there should be little variability amongst a suite of virulence factors than can be assayed in the lab. Alternatively, clinical and environmental isolates can have genomic similarity while displaying phenotypic heterogeneity [22][23][24].…”

Proteomic profiling spotlights the molecular targets and the impact of the natural antivirulent umbelliferone on stress response, virulence factors, and the quorum sensing network of Pseudomonas aeruginosa

“…P. aeruginosa is a ubiquitous, Gram-negative, monoflagellated pathogen that causes serious life-threatening infections, especially in those who have a weak immune system or individuals suffering from any disease. It is a common causative agent of bacteremia in burn victims, urinary tract infections in catheterized patients, ocular infections, and hospital-acquired pneumonia in ventilator-dependent patients ( Bodey et al., 1983 ; Berra et al., 2010 ; Dave et al., 2020 ; Habboush et al., 2021 ; Kunwar et al., 2021 ; Newman et al., 2022 ). Furthermore, P. aeruginosa adapt to cystic fibrosis (CF) airways and survive as overpowering, pervasive, and ineradicable infectious agents until the patient dies ( Döring et al., 2000 ).…”