Bacitracin resistance and enhanced virulence of Streptococcus suis via a novel efflux pump

BMC Vet Res. 2019 Oct 28;15(1):377. doi: 10.1186/s12917-019-2115-2.

Abstract

Background: Streptococcus suis is a prominent pathogen causing septicemia and meningitis in swine and humans. Bacitracin is used widely as a growth promoter in animal feed and to control the spread of necrotic enteritis in most developing countries. This study aimed to characterize a novel membrane transporter module Sst comprising SstE, SstF, and SstG for bacitracin resistance.

Results: Comparative genomics and protein homology analysis found a potential efflux pump SstFEG encoded upstream of well-known bacitracin-resistance genes bceAB and bceRS. A four-fold decrease in bacitracin susceptibility was observed in sstFEG deletion mutant comparing with S. suis wildtype strain CZ130302. Further studies indicated that the bacitracin tolerance mediated by SstFEG is not only independent of the BceAB transporter, but also regulated by the two-component system BceSR. Given that SstFEG are harbored by almost all virulent strains, but not in the avirulent strains, we managed to explore its potential role in bacterial pathogencity. Indeed, our results showed that SstFEG is involved in S. suis colonization and virulence in animal infection model by its potential competitive survival advantage against host bactericidal effect.

Conclusion: To our knowledge, this is the first study to functionally characterize the bacitracin efflux pump in S. suis to provide evidence regarding the important roles of the novel ABC transporter system SstFEG with respect to drug resistance and virulence.

Keywords: Bacitracin; Efflux pump; Serotype Chz; SstFEG; Streptococcus suis; Virulence.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents, Local / metabolism
  • Anti-Infective Agents, Local / pharmacology
  • Bacitracin / metabolism
  • Bacitracin / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial*
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Bacterial
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Streptococcal Infections / microbiology
  • Streptococcus suis / drug effects*
  • Streptococcus suis / metabolism
  • Streptococcus suis / pathogenicity
  • Virulence

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents, Local
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Bacitracin