Dataset Information

Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum ?-lactamases in Klebsiella pneumoniae.

ABSTRACT: Eight Klebsiella pneumoniae clinical strains with high-level aminoglycoside resistance were collected from eight hospitals in São Paulo State, Brazil, in 2010 and 2011. Three of them produced an RmtD group 16S rRNA methyltransferase, RmtD1 or RmtD2. Five strains were found to produce a novel 16S rRNA methyltransferase, designated RmtG, which shared 57 to 58% amino acid identity with RmtD1 and RmtD2. Seven strains coproduced KPC-2 with or without various CTX-M group extended-spectrum ?-lactamases, while the remaining strain coproduced CTX-M-2.

SUBMITTER: Bueno MF

PROVIDER: S-EPMC3632927 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum β-lactamases in Klebsiella pneumoniae.

Bueno Maria Fernanda C MF Francisco Gabriela R GR O'Hara Jessica A JA de Oliveira Garcia Doroti D Doi Yohei Y

Antimicrobial agents and chemotherapy 20130304 5

Eight Klebsiella pneumoniae clinical strains with high-level aminoglycoside resistance were collected from eight hospitals in São Paulo State, Brazil, in 2010 and 2011. Three of them produced an RmtD group 16S rRNA methyltransferase, RmtD1 or RmtD2. Five strains were found to produce a novel 16S rRNA methyltransferase, designated RmtG, which shared 57 to 58% amino acid identity with RmtD1 and RmtD2. Seven strains coproduced KPC-2 with or without various CTX-M group extended-spectrum β-lactamases ...[more]

PMID: 23459483

Similar Datasets

Project description:The most common mechanism of resistance to β-lactam antibiotics in Gram-negative bacteria is the production of β-lactamases that hydrolyze the drugs. Class A β-lactamases are serine active-site hydrolases that include the common TEM, CTX-M, and KPC enzymes. The TEM enzymes readily hydrolyze penicillins and older cephalosporins. Oxyimino-cephalosporins, such as cefotaxime and ceftazidime, however, are poor substrates for TEM-1 and were introduced, in part, to circumvent β-lactamase-mediated resistance. Nevertheless, the use of these antibiotics has lead to evolution of numerous variants of TEM with mutations that significantly increase the hydrolysis of the newer cephalosporins. The CTX-M enzymes emerged in the late 1980s and hydrolyze penicillins and older cephalosporins and derive their name from the ability to also hydrolyze cefotaxime. The CTX-M enzymes, however, do not efficiently hydrolyze ceftazidime. Variants of CTX-M enzymes, however, have evolved that exhibit increased hydrolysis of ceftazidime. Finally, the KPC enzyme emerged in the 1990s and is characterized by its broad specificity that includes penicillins, most cephalosporins, and carbapenems. The KPC enzyme, however, does not efficiently hydrolyze ceftazidime. As with the TEM and CTX-M enzymes, variants have recently evolved that extend the spectrum of KPC β-lactamase to include ceftazidime. This review discusses the structural and mechanistic basis for the expanded substrate specificity of each of these enzymes that result from natural mutations that confer oxyimino-cephalosporin resistance. For the TEM enzyme, extended-spectrum mutations act by establishing new interactions with the cephalosporin. These mutations increase the conformational heterogeneity of the active site to create sub-states that better accommodate the larger drugs. The mutations expanding the spectrum of CTX-M enzymes also affect the flexibility and conformation of the active site to accommodate ceftazidime. Although structural data are limited, extended-spectrum mutations in KPC may act by mediating new, direct interactions with substrate and/or altering conformations of the active site. In many cases, mutations that expand the substrate profile of these enzymes simultaneously decrease the thermodynamic stability. This leads to the emergence of additional global suppressor mutations that help correct the stability defects leading to increased protein expression and increased antibiotic resistance.

Dataset Information

Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum ?-lactamases in Klebsiella pneumoniae.

Publications

Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum β-lactamases in Klebsiella pneumoniae.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets