ZFIN ID: ZDB-PUB-070629-18
SalY of the Streptococcus pyogenes Lantibiotic Locus Is Required for Full Virulence and Intracellular Survival in Macrophages
Phelps, H.A., and Neely, M.N.
Date: 2007
Source: Infection and Immunity   75(9): 4541-4551 (Journal)
Registered Authors: Neely, Melody N.
Keywords: none
MeSH Terms:
  • ATP-Binding Cassette Transporters/genetics
  • ATP-Binding Cassette Transporters/physiology*
  • Animals
  • Bacterial Proteins/genetics
  • Bacterial Proteins/physiology*
  • Bacteriocins/genetics*
  • Cell Line
  • Disease Models, Animal
  • Genetic Markers
  • Intracellular Fluid/microbiology*
  • Macrophages/microbiology*
  • Mice
  • Streptococcal Infections/microbiology
  • Streptococcus pyogenes/genetics
  • Streptococcus pyogenes/growth & development
  • Streptococcus pyogenes/pathogenicity*
  • Zebrafish/microbiology
PubMed: 17576754 Full text @ Infect. Immun.
Streptococcus pyogenes utilizes numerous mechanisms for evading the host immune response, but has only recently been found to survive in the intracellular environment. In this study, we demonstrate the requirement of a putative ABC transporter permease for intracellular survival in macrophages. The highly attenuated S. pyogenes mutant, SalY, was identified from a transposon mutagenesis screen, with over 200-fold attenuation in virulence in a zebrafish invasive disease model. Sequencing of the region surrounding the insertion identified a locus that is highly conserved in other S. pyogenes genomes and is homologous to an operon involved in lantibiotic production. In vitro analysis demonstrated that the SalY mutant is deficient in intracellular survival in murine macrophages, a phenotype also observed in zebrafish macrophages in vivo. Macrophage crude cell lysates added to bacterial cultures resulted in death of the SalY mutant, but only growth inhibition of the wild type strain. Specific depletion of zebrafish macrophages in vivo restored the ability of the SalY mutant to cause disease to wild type levels. The SalY-infected, macrophage-depleted zebrafish exhibit large lesions and invasive dissemination at a similar rate and level as wild type. In contrast, an M protein mutant with a similar degree of attenuation as the SalY mutant did not regain full virulence by in vivo depletion of macrophages. The putative SalY ABC transporter may be an example of the ability of S. pyogenes to adapt and evolve new survival strategies that allow dissemination and growth in previously uninhabitable sites.