Characterization of a SPM-1 metallo-beta-lactamase-producing Pseudomonas aeruginosa by comparative genomics and phenotypic analysis

Abstract

Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of the bla SPM-1 gene, encoding a metallo-beta-lactamase, in combination with other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify key features of their physiology that may lead to the identification of new targets for therapy. Using both illumina and pacBio sequencing data, we obtained a single contig representing the CCBH4851 genome with annotated features that were consistent with data reported for the species. However, comparative analysis with other Pseudomonas aeruginosa strains revealed genomic differences regarding virulence factors and regulatory proteins. In addition, we performed phenotypic assays that revealed CCBH4851 is impaired in bacterial motilities and biofilm formation. On the other hand, CCBH4851 genome contained acquired genomic islands that carry transcriptional factors, virulence and antimicrobial resistance-related genes. presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations may also influence the multidrug-resistant behavior of CCBH4851. Overall, characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed the presence of features that strongly relates to the virulence and antibiotic resistance profile of this important infectious agent. Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections in hospitalized individuals worldwide. Multidrug-resistant (MDR) isolates, particularly those non-susceptible to carbapenems, have become a major concern of health institutions. In addition to mechanisms such as loss of porins or overexpression of efflux pumps, carbapenem resistance is produced by the acquisition of genes encoding carbapenem-hydrolyzing beta-lactamases 1. These enzymes are classified into classes A and D, the activesite serine beta-lactamases (SBLs), and class B, the zinc-dependent or metallo-beta-lactamases (MBLs). SBLs have a broad spectrum of activity against beta-lactams but are inhibited by common beta-lactamase inhibitors.

Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying blaVIM–2 and blaKPC–2 Genes That Spread on Different Genetic Environment in Colombia

“…In addition, sequencing confirmed the presence of mutations in antimicrobial resistance-associated genes in some of the clinical isolates using P. aeruginosa PAO1 as a reference (Table 1). In general, some mutations in quinolone resistance determining regions (QRDRs) of GyrA, ParC, and ParE detected have been previously linked to fluoroquinolone resistance as well as the overexpression of efflux pump systems (Dunham et al, 2010;Subedi et al, 2018;Do Nascimento et al, 2020). In some isolates, the mexZ, nfxB, mexT, and mexR genes, which regulate the MexXY-OprM, MexCD-OprJ, MexEF-OprN, and MexAB-OprM multidrug efflux systems, revealed the presence of several point mutations predicted to result in several amino acid substitutions associated with resistance previously reported (Monti et al, 2013;López-Causapé et al, 2018b;Neves et al, 2019;Olsson et al, 2020).…”

An updated gene regulatory network reconstruction of multidrug-resistant Pseudomonas aeruginosa CCBH4851

“…The structural differences between CCBH-2022 and PA01-2020 results from additional information available due to the new version of PAO1 and recent experimental work on characterising the complete closed genome of P. aeruginosa CCBH4851. 104 …”

Comparative Genomic Analysis of Multi-Drug Resistant Pseudomonas aeruginosa Sequence Type 235 Isolated from Sudan

“…Pseudomonas aeruginosa (P. aeruginosa ) is an aerobic, non-spore forming, Gram negative rods gamma proteobacterium [ 1 ]. The genome size of P. aeruginosa can reach 7.3 Mb, which contains core genes plus variable accessory genes [ 2 ]. P. aeruginosa is frequently associated with a wide range of acute and chronic infections, particularly infections of chronic wounds, such as pressure ulcers, diabetic ulcers, and venous ulcers, in addition to pneumonia in cystic fibrosis and cancer patients taking chemotherapy [ 3 , 4 ].…”