Klebsiella pneumoniae Sequence Type 11 Isolate Producing RmtG 16S rRNA Methyltransferase from a Patient in Miami, Florida

Hu, Fupin; Munoz-Price, L. Silvia; Depascale, Dennise; Rivera, Jesabel I.; Doi, Yohei

doi:10.1128/aac.02632-14

Cited by 10 publications

(10 citation statements)

References 10 publications

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“…First identified in KPC-producing K pneumoniae clinical isolates in Brazil, 53 it has been found in Chile and Miami, all in K pneumoniae . 60,61 rmtG is flanked downstream by IS Vsa3 , but this insertion sequence likely belongs to the site of insertion of the module carrying rmtG rather than the rmtG -containing module itself. 62 There are currently no data on the epidemiology of rmtG .…”

Section: Acquired 16s Ribosomal Rna Methyltransferases In Gram-negatimentioning

confidence: 99%

Aminoglycoside Resistance

Doi

Wachino

Arakawa

2016

Infectious Disease Clinics of North America

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275

125

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Section: Acquired 16s Ribosomal Rna Methyltransferases In Gram-negatimentioning

confidence: 99%

Aminoglycoside Resistance

Doi

Wachino

Arakawa

2016

Infectious Disease Clinics of North America

Self Cite

275

125

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“…The emergence of clones coproducing 16S rRNA methyltransferases further complicates the treatment of infections due to these pathogens, with extremely limited therapeutic options left. The occurrence in Switzerland of a K. pneumoniae clone co-producing KPC-2 and RmtG, with the latter enzyme being so far reported in America and India (Bueno et al, 2013;Filgona et al, 2015;Hu et al, 2014;Poirel et al, 2014), underlines how importation of multidrug-resistant clones may occur despite the high standards of antibiotic stewardship programs and hygiene control in effect in the Swiss healthcare institutions.…”

mentioning

confidence: 99%

Klebsiella pneumoniae co-producing KPC and RmtG, finally targeting Switzerland

Mancini

Poirel

Corthesy

et al. 2018

Diagnostic Microbiology and Infectious Disease

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“…Despite its remarkably low affinity for SAM and SAH, our structure and modeling show that Kmr retains all of the critical elements of the SAM binding pocket through its common class I methyltransferase core fold as well as those specific to the 16S rRNA (m 1 A1408)-modifying enzymes within the ␤6/7 linker. The base of the SAM binding pocket in Kmr is formed by a conserved GxGxG motif (Kmr amino acids 32 GTGDG 36 ) which spans core strand ␤1 and the following loop ( Fig. 5 and 6).…”

Section: Resultsmentioning

confidence: 99%

“…While aminoglycoside-modifying enzymes remain the predominant resistance mechanism among human and animal bacterial pathogens, aminoglycoside resistance-conferring 16S rRNA methyltransferases are increasingly being identified in clinical and veterinary isolates (11,(31)(32)(33). The ease of their spread among pathogens within mobile genetic elements and the broad, high-level resistance conferred by these rRNA modification enzymes make them a profound threat to the future usefulness of aminoglycosides (34,35).…”

Section: Discussionmentioning

confidence: 99%

30S Subunit-Dependent Activation of the Sorangium cellulosum So ce56 Aminoglycoside Resistance-Conferring 16S rRNA Methyltransferase Kmr

Savic

Sunita

Zelinskaya

et al. 2015

Antimicrob Agents Chemother

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bMethylation of bacterial 16S rRNA within the ribosomal decoding center confers exceptionally high resistance to aminoglycoside antibiotics. This resistance mechanism is exploited by aminoglycoside producers for self-protection while functionally equivalent methyltransferases have been acquired by human and animal pathogenic bacteria. Here, we report structural and functional analyses of the Sorangium cellulosum So ce56 aminoglycoside resistance-conferring methyltransferase Kmr. Our results demonstrate that Kmr is a 16S rRNA methyltransferase acting at residue A1408 to confer a canonical aminoglycoside resistance spectrum in Escherichia coli. Kmr possesses a class I methyltransferase core fold but with dramatic differences in the regions which augment this structure to confer substrate specificity in functionally related enzymes. Most strikingly, the region linking core ␤-strands 6 and 7, which forms part of the S-adenosyl-L-methionine (SAM) binding pocket and contributes to base flipping by the m 1 A1408 methyltransferase NpmA, is disordered in Kmr, correlating with an exceptionally weak affinity for SAM. Kmr is unexpectedly insensitive to substitutions of residues critical for activity of other 16S rRNA (A1408) methyltransferases and also to the effects of by-product inhibition by S-adenosylhomocysteine (SAH). Collectively, our results indicate that adoption of a catalytically competent Kmr conformation and binding of the obligatory cosubstrate SAM must be induced by interaction with the 30S subunit substrate. Gene pools in soil and aquatic microbial communities represent largely unexplored reservoirs of antibiotic resistance (1, 2). An analysis of the resistance mechanisms present in these communities may reveal new insights into the origins, activities, and potential for mobilization of antibiotic resistance determinants to pathogenic bacterial populations. In particular, myxobacteria of the genus Sorangium have become a major source of secondary metabolites over the last several decades alongside the actinobacteria and fungi (3, 4). The model strain Sorangium cellulosum So ce56 possesses a 13.1-Mb genome with 17 gene clusters for secondary metabolites (5). Associated with this tremendous biosynthetic power is a high resistance potential against multiple antibiotics. For example, all Sorangium strains can grow in the presence of exceptionally high concentrations of kanamycin through the action of a single, specific aminoglycoside resistance-conferring 16S rRNA methyltransferase, Kmr (6).In common with most aminoglycosides, kanamycin binds within helix (h) 44 of the 16S rRNA in the bacterial small (30S) ribosomal subunit and induces errors in mRNA decoding (7-9). Aminoglycoside-producing bacteria typically protect themselves from self-intoxication by expression of aminoglycoside resistance-conferring methyltransferases that modify the drug binding site. Two subfamilies of 16S rRNA methyltransferases introduce distinct 16S rRNA modifications at N7 of guanosine 1405 (m 7 G1405) or N1 of adenosine 1408 (m 1 A140...

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Klebsiella pneumoniae Sequence Type 11 Isolate Producing RmtG 16S rRNA Methyltransferase from a Patient in Miami, Florida

Cited by 10 publications

References 10 publications

Aminoglycoside Resistance

Aminoglycoside Resistance

Klebsiella pneumoniae co-producing KPC and RmtG, finally targeting Switzerland

30S Subunit-Dependent Activation of the Sorangium cellulosum So ce56 Aminoglycoside Resistance-Conferring 16S rRNA Methyltransferase Kmr

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