Spread of Plasmid-Encoded NDM-1 and GES-5 Carbapenemases among Extensively Drug-Resistant and Pandrug-Resistant Clinical Enterobacteriaceae in Durban, South Africa

Abstract

Whole-genome sequence analyses revealed the presence of ( = 31), ( = 8), ( = 1), or ( = 1) in extensively drug-resistant and pandrug-resistant organisms isolated from in-patients in 10 private hospitals (2012 to 2013) in Durban, South Africa. Two novel NDM-1-encoding plasmids from were circularized by PacBio sequencing. In p19-10_01 [IncFIB(K); 223.434 bp], was part of a Tn-like structure (16.276 bp) delineated by IS The multireplicon plasmid p18-43_01 [IncR_1/IncFIB(pB171)/IncFII(Yp); 212.326 bp] shared an 80-kb region with p19-10_01, not including the -containing region. The two plasmids were used as references for tracing NDM-1-encoding plasmids in the other genome assemblies. The p19-10_01 sequence was detected in ( = 7) only, whereas p18-43_01 was tracked to ( = 4), ( = 1), ( = 11), spp. ( = 7), and ( = 1), revealing horizontal spread of this -bearing plasmid structure. Global phylogeny showed clustering of the (18/20) isolates together with closely related carbapenemase-negative ST101 isolates from other geographical origins. The South African isolates were divided into three phylogenetic subbranches, where each group had distinct resistance and replicon profiles, carrying either p19-10_01, p18-10_01, or pCHE-A1 (8,201 bp). The latter plasmid carried and within an integron mobilization unit. Our findings imply independent plasmid acquisition followed by local dissemination. Additionally, we detected carried by pPKPN4 in (ST14) and contained by a pNDM-MGR194-like genetic structure in (ST167), adding even more complexity to the multilayer molecular mechanisms behind nosocomial spread of carbapenem-resistant in Durban, South Africa.

Plasmid evolution in carbapenemase‐producing Enterobacteriaceae: a review

“…This pEB‐1 plasmid was compared with other L/M plasmids, pEL60 and pNDM‐OM, and similar characteristics were observed, except that the integration site of the ARGs array was different . In South Africa, bla GES‐5 was reported on an IncQ plasmid but still within a class 1 integron, with an additional aadA4 on an integron mobilization unit …”

“…Additionally, GES‐5 has been described in Pseudomonas spp. and Enterobacteriaceae , and has been widely reported in South America, with a few reports in Canada, the Czech Republic, Turkey, Portugal, South Africa, and South Korea . Other GES variants are also reported, although rarely …”

“…More than 20 KPC variants have been described, but KPC‐2 and KPC‐3 are most reported and widely distributed . KPCs have been reported in several K. pneumoniae sequence types (ST), although ST258, ST11, and, more recently, ST101, are the major players associated with pandemic spread …”

“…Carbapenem resistance is mainly driven by carbapenemases found on mobile genetic elements (MGEs), such as integrons, insertion sequences, transposons, and mobile plasmids, that can shuttle carbapenemase‐expressing genes within and across bacterial cells of the same or different species . The ability of plasmids to carry multiple antibiotic resistance genes (ARGs) and be mobilized across same and different species via conjugation make them very important in the molecular epidemiology of CREs . This is further complicated by the ability of multiple plasmids, depending on their incompatibility (Inc), to be harbored in a single CRE cell.…”

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

“…Horizontal gene transfer (HGT) allows a significant genetic diversity to be amassed from other unrelated bacteria as opposed to vertical gene transfer . It has been shown that HGT remains the most effective means of bacterial evolution, as it allows bacteria to rapidly acquire new genomic traits, such as virulence and resistance determinants with the help of MGEs .…”