LdtMav2, a nonclassical transpeptidase and susceptibility of Mycobacterium avium to carbapenems

Future Microbiol. 2017 Jun;12(7):595-607. doi: 10.2217/fmb-2016-0208. Epub 2017 May 30.

Abstract

Aim: Mycobacterium avium infections, especially in immune-compromised individuals, present a significant challenge as therapeutic options are limited. In this study, we investigated if M. avium genome encodes nonclassical transpeptidases and if newer carbapenems are effective against this mycobacteria.

Materials & methods: Biochemical and microbiological approaches were used to identify and characterize a nonclassical transpeptidase, namely L,D-transpeptidase, in M. avium.

Results & conclusion: We describe the biochemical and physiological attributes of a L,D-transpeptidase in M. avium, LdtMav2. Suggestive of a constitutive requirement, levels of LdtMav2, a L,D-transpeptidase in M. avium, remain constant during exponential and stationary phases of growth. Among β-lactam antibacterials, only a subset of carbapenems inhibit LdtMav2 and tebipenem, a new oral carbapenem, inhibits growth of M. avium.

Keywords: L,D-transpeptidase; Mycobacterium avium; carbapenem; mycobacteria; peptidoglycan; tebipenem.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology*
  • Crystallography, X-Ray
  • Drug Resistance, Multiple, Bacterial
  • Genome, Bacterial
  • Mycobacterium avium Complex / drug effects*
  • Mycobacterium avium Complex / enzymology*
  • Mycobacterium avium Complex / genetics
  • Mycobacterium avium Complex / growth & development
  • Peptidyl Transferases / chemistry*
  • Peptidyl Transferases / genetics*
  • Peptidyl Transferases / isolation & purification
  • Peptidyl Transferases / metabolism
  • Sequence Analysis, DNA
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • beta-Lactams
  • Peptidyl Transferases
  • tebipenem