Genomic analysis of a multidrug‐resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon

Abstract

Whole‐genome sequence analysis was performed on a multidrug‐resistant Providencia rettgeri PR002 clinical strain isolated from the urine of a hospitalized patient in Pretoria, South Africa, in 2013. The resistome, mobilome, pathogenicity island(s), as well as virulence and heavy‐metal resistance genes of the isolate, were characterized using whole‐genome sequencing and bioinformatic analysis. PR002 had a genome assembly size of 4,832,624 bp with a GC content of 40.7%, an A/C2 plasmid replicase gene, four integrons/gene cassettes, 17 resistance genes, and several virulence and heavy metal resistance genes, confirming PR002 as a human pathogen. A novel integron, In1483, harboring the gene blaOXA‐2, was identified, with other uncharacterized class 1 integrons harboring aacA4cr and dfrA1. Aac(3′)‐IIa and blaSCO‐1, as well as blaPER‐7, sul2, and tet(B), were found bracketed by composite Tn3 transposons, and IS91, IS91, and IS4 family insertion sequences, respectively. PR002 was resistant to all antibiotics tested except amikacin, carbapenems, cefotaxime‐clavulanate, ceftazidime‐clavulanate, cefoxitin, and fosfomycin. PR002 was closely related to PR1 (USA), PRET_2032 (SPAIN), DSM_1131, and NCTC7477 clinical P. rettgeri strains, but not close enough to suggest it was imported into South Africa from other countries. Multidrug resistance in P. rettgeri is rare, particularly in clinical settings, making this case an important incident requiring urgent attention. This is also the first report of an A/C plasmid in P. rettgeri. The array, multiplicity, and diversity of resistance and virulence genes in this strain are concerning, necessitating stringent infection control, antibiotic stewardship, and periodic resistance surveillance/monitoring policies to preempt further horizontal and vertical spread of these resistance genes.

Pathogenomics and Evolutionary Epidemiology of Multi-Drug Resistant Clinical Klebsiella pneumoniae Isolated from Pretoria, South Africa

“…Integron 191 was however identified in four different STs suggesting a diversity of clones with this MGE. The dominance of the class 1 integron in this study is also consistent with genomes found in Africa, Europe and South America 8,31,41,44 . Two novel integrons identified had the aadA16 cassette variant in K021 as well as dfr30b and dfrA14b cassette variants in K145, confirming the ongoing evolutionary processes in these genomes resulting in the diversity of gene cassettes in K. pneumoniae.…”

“…The presence of the bla CTX-M , bla TEM , bla OXA , and bla SHV ESBL genes in similar genetic contexts have been described previously in same and different species in South African and international isolates 7,8,12,19,20,[31][32][33][34][35][36] . The presence of these ARGs within the same genetic context and on the same plasmid replicons across same and different species around the globe strongly suggests the clonal and plasmid-mediated spread of these ARGs.…”

“…2-7), commonly encode resistance to β-lactams [45][46][47][48] ; this synteny and genetic environment were also observed in E. coli from the same hospitals 12 . This rich diversity of transposons and ISs obviously contribute to the genome plasticity, ARGs composition and HGT of ARGs within and across the www.nature.com/scientificreports www.nature.com/scientificreports/ strains 6,8,10 . None of the isolates carried Tn21, which was shown to carry multiple resistance genes in a Kenyan study, and was associated with the transfer of antimicrobial resistance in these isolates 44 .…”

Phylogeography and Resistome Epidemiology of Gram-Negative Bacteria in Africa: A Systematic Review and Genomic Meta-Analysis from a One-Health Perspective

“…These species have been implicated in fatal infections such as sepsis and wound infections 31,34,39,62,63 , bearing critical ARGs such as ESBLs and carbapenemases ( Fig. S11, S20, S24-S25).…”

Pathogenomic Analysis of a Novel Extensively Drug-Resistant Citrobacter freundii Isolate Carrying a blaNDM-1 Carbapenemase in South Africa

“…Resistance to ciprofloxacin was mediated by GyrA [S83I] chromosomal mutation, plasmid-mediated quinolone resistance genes (PMQR) (aac(6')-Ib-cr and qnrB1), and efflux genes ( [15] reported that high-level fluroquinolone resistance was mediated by efflux, PMQR genes, and gyrA mutations in Enterobacterales, including Citrobacter freundii, which supported our results. More so, efflux genes belonging to three main efflux pump systems ( Table 2) reported to play vital roles in antibiotic resistance in Enterobacterales were also identified [18,19]. However, the mere presence of these efflux genes does not directly implicate resistance, and hence further studies on their expression levels will be needed to ascertain the possibility of efflux pump hyperexpression [18].…”