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Drug Design Reviews - Online (Discontinued)

Editor-in-Chief

ISSN (Print): 1567-2697
ISSN (Online): 1567-2697

Genomic and Structural Diversity of Antiseptic Resistance Gene smr Encoding Multidrug Efflux Protein in Staphylococci

Author(s): Nobumichi Kobayashi, Mohammed Mahbub Alam, Masaho Ishino and Keiji Mise

Volume 1, Issue 4, 2004

Page: [303 - 312] Pages: 10

DOI: 10.2174/1567269043390528

Price: $65

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Abstract

Antiseptic resistance of staphylococci is caused by multidrug transporter proteins represented by QacA / QacB and Smr / QacC which mediate efflux of drugs via electrochemical proton gradient across the cytoplasmic membrane. Smr / QacC is a member of small multidrug resistance (SMR) family which consists of approximately 110 amino acids and contains four predicted transmembrane segments. SMR family includes various antiseptic resistance proteins which have been found in staphylococci as well as in other bacterial species. Phylogenetically, SMR family proteins are classified into two major clusters, genogroup 1 and genogroup 2, which are mostly found in Gram-positive cocci and Gram-negative bacteria, respectively. Although amino acid sequences of SMR family are divergent among different genotypes, several amino acids in transmembrane regions are highly conserved and considered to be directly associated with a process of drug transport through the bacterial cytoplasmic membrane. The Smr / QacC which is encoded by smr is genetically well conserved in staphylococci. However, genomic diversity is found outside the ORF of smr gene and three types of smr gene cassette (Types 1, 2, and 3) which is a structural unit containing smr and terminal direct repeats (DRs) have been discriminated. Although antiseptic resistance levels of Staphylococcus aureus having smr in each of the three types of cassettes were generally similar, higher copy numbers were detected for type 2 cassette-smr than type 1 cassettesmr in our recent study, suggesting that expression level of smr might be different depending on the type of smr gene cassette. Further study of genomic structure and diversity of smr gene will contribute to prevent spread of antiseptic resistance in staphylococci and development of novel antiseptic substances.

Keywords: antiseptic, resistance, efflux, staphylococcus, smr, diversity


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