High-level resistance to mecillinam produced by inactivation of soluble lytic transglycosylase in Salmonella enterica serovar Typhimurium

FEMS Microbiol Lett. 2006 Mar;256(2):311-7. doi: 10.1111/j.1574-6968.2006.00133.x.

Abstract

By screening for high-level mecillinam resistant derivatives of a low-level resistant strain (cysB403 galE1922 relA21::Tn10) of Salmonella enterica serovar Typhimurium, a MudJ insertion in the gene for soluble lytic transglycosylase (slt) was isolated. This insertion (slt-1::MudJ) increased the resistance to mecillinam of cysB and cysE strains (MIC: about 20-40 microg mL(-1)) to a strikingly high level (MIC: 160 microg mL(-1)). As in Escherichia coli K-12, the slt mutation slightly increased the sensitivity of the wild type and of several strains that carried mutations that did not increase mecillinam resistance. All the strains acquired a spherical cell shape when treated with mecillinam. The effect of slt-1::MudJ was limited to mecillinam, the response to several other antibiotics remaining unaltered by the insertion. The results presented in this paper demonstrate that soluble lytic transglycosylase performs an important role in the response to mecillinam, which only becomes evident when failure of CysB/CysE function causes medium-level resistance. The results also suggest that soluble lytic transglycosylase interacts with, and is partially inhibited by normal lipopolysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Amdinocillin / metabolism
  • Amdinocillin / pharmacology*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial
  • Escherichia coli Proteins
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism*
  • Microbial Sensitivity Tests
  • Mutagenesis, Insertional
  • Mutation
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / enzymology*
  • Serine O-Acetyltransferase

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • CysB protein, Bacteria
  • Escherichia coli Proteins
  • Acetyltransferases
  • CysE protein, E coli
  • Serine O-Acetyltransferase
  • Glycosyltransferases
  • murein transglycosylase
  • Amdinocillin