Document Type

Honors Thesis

Publication Date

Spring 5-2018

Abstract

Streptococcus pyogenes, the etiologic agent for several life-threatening invasive diseases, utilizes numerous mechanisms to evade the host immune response and establish a successful infection causing a significant source of morbidity and mortality risks for patients. The bacterium is known to cause necrotizing fasciitis in both humans and zebrafish, with extensive necrotic damage to tissues but surprisingly lacking in an inflammatory response for a systemic infection. This suggests that the recruitment of inflammatory cells to the site of infection is inhibited. To observe this in real-time, we used the zebrafish model of Streptococcal pathogenesis to analyze immune cell recruitment in the attenuated putative ABC transporter permease mutant, SalY, and lantibiotic mutant, SalA, to explain the difference in virulence as compared to wild-type. Fluorescence microscopy using transgenic zebrafish with fluorescent immune cells reveals increased co-localization with macrophages in larvae infected with SalY mutant and a two-fold increase in the number of macrophages recruited early on to the site of infection compared to wild type. Bacterial recovery of SalY-mutant infection significantly decreased by nearly 85% compared to wild type. SalA mutant exhibited comparable observations to SalY mutant in immune cell recruitment and bacterial recovery. Further characterization of conserved genes of the Salivaricin locus in relation to their function in immunity will provide insight into a new mechanism for immune evasion and potentially lead to the development of novel antimicrobials to help address the significant healthcare burden posed by this pathogen.

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