Expansion of acquired 16S rRNA methytransferases along with CTX-M-15, NDM and OXA-48 within three sequence types of Escherichia coli from northeast India
Abstract:Background
This study aimed to identify ten different 16S rRNA methyltransferase genes (
rmtA, rmtB, rmtC, rmtD, armA, rmtF, npmA, rmtH, rmtE
and
rmtG)
and their coexisting ESBL and carbapenemase with the emergence of three
E.coli
clones within a single study centre.
Methods
A total of 329 non-duplicate
E.coli
isolates were studied to detect the presence of 16S rR… Show more
“…p1632-2 was another resistance plasmid harboring the armA gene. armA is a common element that conferred the high-level aminoglycoside phenotype that can be observed in the chromosome or multiple plasmids, belonging to different incompatibility groups (IncM2, IncFII, IncR, IncX1, and IncN) ( 20 – 24 ). In this study, the p1632-2 plasmid was typed as IncM2 plasmid and had an extremely high-conjugative frequency, higher than the other IncM2- armA plasmid pMS3802OXARMA studied before (10 −1 versus 10 −4 ) ( 25 ).…”
Carbapenemase-producing
Klebsiella pneumoniae
have become a great challenge for antimicrobial chemotherapy, while aminoglycosides can lower the mortality rate effectively in combination therapy with them. Unfortunately, we isolated two
K. pneumoniae
from blood sample of patients that not only exhibited high-level resistance to carbapenems and aminoglycosides but also showed the unusual co-occurrence of the
rmtB
,
armA
, and
bla
KPC-2
genes.
“…p1632-2 was another resistance plasmid harboring the armA gene. armA is a common element that conferred the high-level aminoglycoside phenotype that can be observed in the chromosome or multiple plasmids, belonging to different incompatibility groups (IncM2, IncFII, IncR, IncX1, and IncN) ( 20 – 24 ). In this study, the p1632-2 plasmid was typed as IncM2 plasmid and had an extremely high-conjugative frequency, higher than the other IncM2- armA plasmid pMS3802OXARMA studied before (10 −1 versus 10 −4 ) ( 25 ).…”
Carbapenemase-producing
Klebsiella pneumoniae
have become a great challenge for antimicrobial chemotherapy, while aminoglycosides can lower the mortality rate effectively in combination therapy with them. Unfortunately, we isolated two
K. pneumoniae
from blood sample of patients that not only exhibited high-level resistance to carbapenems and aminoglycosides but also showed the unusual co-occurrence of the
rmtB
,
armA
, and
bla
KPC-2
genes.
“…proteins such as NDM-1 and CTX-M-15 [15][16][17]. The RmtE2 variant, with a single amino acid modification compared with RmtE1, was only described in two E. coli isolates from two diseased pigs in China in 2015, encoded in an IncI1 plasmid [18].…”
Antimicrobial resistance (AMR) mechanisms, especially those conferring resistance to critically important antibiotics, are a great concern for public health. 16S rRNA methyltransferases (16S-RMTases) abolish the effectiveness of most clinically used aminoglycosides, but some of them are considered sporadic, such as RmtE. The main goals of this work were the genomic analysis of bacteria producing 16S-RMTases from a ‘One Health’ perspective in Venezuela, and the study of the epidemiological and evolutionary scenario of RmtE variants and their related mobile genetic elements (MGEs) worldwide. A total of 21 samples were collected in 2014 from different animal and environmental sources in the Cumaná region (Venezuela). Highly aminoglycoside-resistant
Enterobacteriaceae
isolates were selected, identified and screened for 16S-RMTase genes. Illumina and Nanopore whole-genome sequencing data were combined to obtain hybrid assemblies and analyse their sequence type, resistome, plasmidome and pan-genome. Genomic collections of rmtE variants and their associated MGEs were generated to perform epidemiological and phylogenetic analyses. A single 16S-RMTase, the novel RmtE4, was identified in five
Klebsiella
isolates from wastewater samples of Cumaná. This variant possessed three amino acid modifications with respect to RmtE1–3 (Asn152Asp, Val216Ile and Lys267Ile), representing the most genetic distant among all known and novel variants described in this work, and the second most prevalent. rmtE variants were globally spread, and their geographical distribution was determined by the associated MGEs and the carrying bacterial species. Thus, rmtE4 was found to be confined to
Klebsiella
isolates from South America, where it was closely related to ISVsa3 and an uncommon IncL plasmid related with hospital environments. This work uncovered the global scenario of RmtE and the existence of RmtE4, which could potentially emerge from South America. Surveillance and control measures should be developed based on these findings in order to prevent the dissemination of this AMR mechanism and preserve public health worldwide.
“…At present, the rmtG gene was still mainly prevalent in South America, especially in K. pneumoniae isolated from Brazil. It also could be found in K. aerogenes, P. aeruginosa, and E. coli isolated in America, India, Switzerland [ 3 , 59 , 96 , 97 , 98 , 100 , 101 ]. However, no strain carrying rmtG has been found in China so far.…”
Section: Plasmid-mediated 16s Rrna Methylase Resistance Gene and Its ...mentioning
confidence: 99%
“…The mechanism of aminoglycosides is to bind the A site of 16S rRNA, which consists of the 30S ribosomal subunit, leading to the inhibition of protein synthesis and bacteria death [ 2 ]. Therefore, aminoglycosides have a broad spectrum of antimicrobial activity against both Gram-positive and Gram-negative bacteria and are often used in combination with β-lactam antibiotics, especially the third-generation cephalosporins [ 3 ].…”
With the wide spread of multidrug-resistant bacteria, a variety of aminoglycosides have been used in clinical practice as one of the effective options for antimicrobial combinations. However, in recent years, the emergence of high-level resistance against pan-aminoglycosides has worsened the status of antimicrobial resistance, so the production of 16S rRNA methyltransferase (16S-RMTase) should not be ignored as one of the most important resistance mechanisms. What is more, on account of transferable plasmids, the horizontal transfer of resistance genes between pathogens becomes easier and more widespread, which brings challenges to the treatment of infectious diseases and infection control of drug-resistant bacteria. In this review, we will make a presentation on the prevalence and genetic environment of 16S-RMTase encoding genes that lead to high-level resistance to aminoglycosides.
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