Abstract
BackgroundThe prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities. Although hundreds of complete genomes of clinical P. aeruginosa isolates have been sequenced, only a few complete genomes of mucoid strains are available, limiting a comprehensive understanding of this important group of opportunistic pathogens. Herein, the complete genome of a clinically isolated mucoid strain P. aeruginosa JNQH-PA57 was sequenced and assembled using Illumina and Oxford nanopore sequencing technologies. Genomic features, phylogenetic relationships, and comparative genomics of this pathogen were comprehensively analyzed using various bioinformatics tools. A series of phenotypic and molecular-genetic tests were conducted to investigate the mechanisms of carbapenem resistance in this strain.ResultsSeveral genomic features of MDR P. aeruginosa JNQH-PA57 were identified based on the whole-genome sequencing. We found that the accessory genome of JNQH-PA57 including several prophages, genomic islands, as well as a PAPI-1 family integrative and conjugative element (ICE), mainly contributed to the larger genome of this strain (6,747,067 bp) compared to other popular P. aeruginosa strains (with an average genome size of 6,445,223 bp) listed in Pseudomonas Genome Database. Colony morphology analysis and biofilm crystal staining assay respectively demonstrated an enhanced alginate production and a thicker biofilm formation capability of JNQH-PA57. A deleted mutation at nt 424 presented in mucA gene, resulted in the upregulated expression of a sigma-factor AlgU and a GDP mannose dehydrogenase AlgD, which might explain the mucoid phenotype of this strain. As for the carbapenem resistance mechanisms, our results revealed that the interplay between impaired OprD porin, chromosomal β-lactamase OXA-488 expression, MexAB-OprM and MexXY-OprM efflux pumps overexpression, synergistically with the alginates-overproducing protective biofilm, conferred the high carbapenem resistance to P. aeruginosa JNQH-PA57.ConclusionBased on the genome analysis, we could demonstrate that the upregulated expression of algU and algD, which due to the truncation variant of MucA, might account for the mucoid phenotype of JNQH-PA57. Moreover, the resistance to carbapenem in P. aeruginosa JNQH-PA57 is multifactorial. The dataset presented in this study provided an essential genetic basis for the comprehensive cognition of the physiology, pathogenicity, and carbapenem resistance mechanisms of this clinical mucoid strain.
Highlights
The prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities
We found that the accessory genome of JNQH-PA57 including several prophages, genomic islands, as well as a PAPI-1 family integrative and conjugative element (ICE), mainly contributed to the larger genome of this strain (6, 747,067 bp) compared to other popular P. aeruginosa strains listed in Pseudomonas Genome Database
As for the carbapenem resistance mechanisms, our results revealed that the interplay between impaired OprD porin, chromosomal βlactamase OXA-488 expression, MexAB-OprM and MexXY-OprM efflux pumps overexpression, synergistically with the alginates-overproducing protective biofilm, conferred the high carbapenem resistance to P. aeruginosa JNQH-PA57
Summary
The prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities. Hundreds of complete genomes of clinical P. aeruginosa isolates have been sequenced, only a few complete genomes of mucoid strains are available, limiting a comprehensive understanding of this important group of opportunistic pathogens. Pseudomonas aeruginosa is an opportunistic pathogen that can cause a wide range of acute and chronic infections. It is responsible for the life-threatening infections in patients with malignancy, immunosuppression, burns, and those who performed mechanical ventilation [1]. Once the chronic infection is established, P. aeruginosa may acquire mutations leading to the conversion of mucoid phenotype, and exhibit reinforced recalcitrance to clearance by the immune system and antimicrobial therapy [9]
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