Network-assisted investigation of virulence and antibiotic-resistance systems in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a Gram-negative bacterium of clinical significance. Although the genome of PAO1, a prototype strain of P. aeruginosa, has been extensively studied, approximately one-third of the functional genome remains unknown. With the emergence of antibiotic-resistant strains of P. aeruginosa, there is an urgent need to develop novel antibiotic and anti-virulence strategies, which may be facilitated by an approach that explores P. aeruginosa gene function in systems-level models. Here, we present a genome-wide functional network of P. aeruginosa genes, PseudomonasNet, which covers 98% of the coding genome, and a companion web server to generate functional hypotheses using various network-search algorithms. We demonstrate that PseudomonasNet-assisted predictions can effectively identify novel genes involved in virulence and antibiotic resistance. Moreover, an antibiotic-resistance network based on PseudomonasNet reveals that P. aeruginosa has common modular genetic organisations that confer increased or decreased resistance to diverse antibiotics, which accounts for the pervasiveness of cross-resistance across multiple drugs. The same network also suggests that P. aeruginosa has developed mechanism of trade-off in resistance across drugs by altering genetic interactions. Taken together, these results clearly demonstrate the usefulness of a genome-scale functional network to investigate pathogenic systems in P. aeruginosa.

Resistome metagenomics from plate to farm: the resistome and microbial composition during food waste feeding and composting on a Vermont poultry farm

“…None of these proved significant however, which prompted the investigation of potential interactions between resistance genes and virulence genes facilitating gene transfer events. Co-occurrence of virulence genes and antibiotic resistance has been shown in Pseudomonas aeruginosa [52] and has a stronger association than antibiotic use alone in populations of E. coli [53,54]. In the current study, this relationship between antibiotic resistance genes and virulence factors produced the only statistically significant result, with Shannon diversities of these gene categories being positively correlated (0.553, P = 0.05).…”

The Microbial Ecosystem Distinguishes Chronically Diseased Tissue from Adjacent Tissue in the Sigmoid Colon of Chronic, Recurrent Diverticulitis Patients

“…However, whether this enrichment is associated with non-specific intestinal inflammation 17 or the diverticular disease process will require further research. Pseudomonas is an organism which in healthcare settings is known to have a broad range of behavior, but with a potential for antibiotic resistance 18 . Animal models of intestinal anastomoses have shown that Pseudomonas can release collagenases in response to tissue injury 19 .…”

Quorum sensing: An imperative longevity weapon in bacteria

“…A network of potential antiquorum sensing agents for P. aeruginosa was created with information from biomedical ontologies and curated databases (Martín et al, 2017). Some groups have already applied network approaches to study antibiotic resistance in P. aeruginosa, while others have tried to extract information types and apply it to the retrieval and curation of research articles in P. aeruginosa QS (Hwang et al, 2016). In V. fischeri, LuxI is an important component of QS signaling pathway (Engebrecht et al, 1987).…”