Pleiotropic regulatory function of the lysr family transcriptional regulator cpsy during streptococcus iniae systemic infection

<p>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 <i>Streptococcus iniae</i> 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. A <i>S. iniae</i> mutant with an in-frame deletion of cpsY is highly attenuated in a zebrafish infection model. The cpsY deletion mutant displays a methionine-independent growth defect in serum, which differs from the methionine-dependent defect observed for orthologous mutants of <i>S. mutans</i> and <i>S. agalactiae</i>. On the contrary, the cpsY deletion mutant can grow in excess of WT when supplemented with proteose peptone, suggesting an inability to properly regulate growth. CpsY is critical for protection of <i>S. iniae</i> from clearance by neutrophils in whole blood, but is dispensable for intracellular survival in macrophages. Susceptibility of the cpsY deletion mutant to killing in whole blood is not due to a growth defect because inhibition of neutrophil phagocytosis rescues the mutant to WT levels. <i>S. iniae</i> does not alter neutrophil phagosomal maturation, but instead is able to adapt to the extreme bactericidal environment of a mature neutrophil phagosome dependent upon CpsY. This CpsY-dependent adaptation appears to involve stabilization of the cell wall in part through peptidoglycan O-acetylation and repression of cellular autolysins. In addition, CpsY may influence these processes by responding to nutritional stress. The ability of a pathogen to evade neutrophil phagocytic killing mechanisms is critically important for dissemination and establishment of a systemic infection. Understanding how pathogens overcome these innate defenses is important for the development of optimal therapeutic strategies for invasive infections. Furthermore <i>S. iniae</i> proves to be a powerful model to investigate bacterial adaptations during systemic streptococcal infection.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Immunology and Microbiology

Year dc:date.available

2011

Author dc:creator

• Allen, Jonathan Paul

Contributors dc:contributor

• Melody N. Neely

• Microbiology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/300

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1299