Mobile lincosamide resistance genes in staphylococci

Plasmid. 2018 Sep;99:22-31. doi: 10.1016/j.plasmid.2018.06.002. Epub 2018 Jun 19.

Abstract

Lincosamide resistance in staphylococci is based on the expression of a number of genes which specify three major resistance mechanisms: (i) enzymatic inactivation by lincosamide nucleotidyltransferases, (ii) ribosome protection by ABC-F proteins, and (iii) methylation of the ribosomal target sites in the 23S rRNA by Cfr or Erm methylases. So far, only two lnu genes, lnu(A) and lnu(B), which code for different types of lincosamide nucleotidyltransferases, have been found in staphylococci. The ABC-F proteins are encoded by genes of the vga, lsa and sal classes. The corresponding proteins exhibit ATP-binding domains, but lack transmembrane regions. So far, vga(A) genes - including the variant genes vga(A)V and vga(A)LC -, vga(C) genes and vga(E) genes - including the variant gene vga(E)V -, the lsa genes lsa(B) and lsa(E), as well as the sal(A) gene have been identified in staphylococci. The aforementioned genes, except lsa(B), confer resistance not only to lincosamides, but also to pleuromutilins and streptogramin A. The cfr and erm genes code for methylases which target the adenine residues at positions 2503 and 2048 in the 23S rRNA, respectively. While the cfr gene confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A, the erm genes mediate resistance to macrolides, lincosamides and streptogramin B. Many of the aforementioned lincosamide resistance genes are located on either plasmids or transposons and as such, can easily be disseminated across strain, species, and genus boundaries. The co-location of other antimicrobial resistance genes on the same mobile genetic element facilitates co-selection and persistence of the lincosamide resistance genes under the selective pressure imposed by other antimicrobial agents.

Keywords: Plasmid; Transposon; cfr gene; lnu genes; lsa genes; vga genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Genes, Bacterial
  • Humans
  • Lincosamides / therapeutic use*
  • Macrolides / adverse effects
  • Macrolides / therapeutic use
  • Plasmids / genetics*
  • RNA, Ribosomal, 23S / genetics
  • Staphylococcus / drug effects
  • Staphylococcus / genetics*
  • Staphylococcus / pathogenicity
  • Streptogramin B / adverse effects
  • Streptogramin B / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Lincosamides
  • Macrolides
  • RNA, Ribosomal, 23S
  • Streptogramin B