title: The Streptococcus iniae transcriptional regulator CpsY is required for protection from neutrophil-mediated killing and proper growth in vitro.
abstract: The ability of a pathogen to metabolically adapt to the local environment for optimal expression of virulence determinants is a continued area of research. Orthologs of the Streptococcus iniae LysR family regulator CpsY have been shown to regulate methionine biosynthesis and uptake pathways but appear to influence expression of several virulence genes as well. An S. iniae mutant with an in-frame deletion of cpsY (ΔcpsY mutant) is highly attenuated in a zebrafish infection model. The ΔcpsY mutant displays a methionine-independent growth defect in serum, which differs from the methionine-dependent defect observed for orthologous mutants of Streptococcus mutans and Streptococcus agalactiae. On the contrary, the ΔcpsY mutant can grow in excess of the wild type (WT) when supplemented with proteose peptone, suggesting an inability to properly regulate growth. CpsY is critical for protection of S. iniae from clearance by neutrophils in whole blood but is dispensable for intracellular survival in macrophages. Susceptibility of the ΔcpsY mutant to killing in whole blood is not due to a growth defect, because inhibition of neutrophil phagocytosis rescues the mutant to WT levels. Thus, CpsY appears to have a pleiotropic regulatory role for S. iniae, integrating metabolism and virulence. Furthermore, S. iniae provides a unique model to investigate the paradigm of CpsY-dependent regulation during systemic streptococcal infection.
authors.affiliation: Wayne State University School of Medicine, Department of Immunology and Microbiology, 540 E. Canfield, Detroit, MI 48201, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Allen
authors.forename: Melody N
authors.initials: MN
authors.lastname: Neely
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology; D008715:Methionine / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D011401:Promoter Regions, Genetic; D013291:Streptococcus / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D008715:Methionine