Date of Award

2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

Streptococcus pyogenes is a Gram-positive aerotolerant bacterium that is an extracellular, non-motile, non-sporulating pathogen. They are clinically important in humans not only because of their pathogenicity but their remarkable ability to adapt to harsh conditions. Viability and virulence of S. pyogenes are reported to be associated with cyclic-di-adenosine monophosphate (c-di-AMP). Proper biosynthesis of this second messenger is essential to maintain ionic balance, homeostasis and cell envelope integrity as it has been reported to be associated with the expression of the virulence factors SpeB which the pathogens use to fight the host immune system leading to infection development. c-di-AMP helps S. pyogenes survive when it is exposed to unfavorable conditions by acting as a signaling molecule. We measure the c-di-AMP level of Streptococcus pyogenes with ionic imbalance, and cell envelope stress and observe its potential to regulate SpeB expression under an elevated external potassium level. The study revealed that KtrAB potassium importer impacts c-di-AMP level markedly, but dltX and liaR gene deletion didnt show visible change in c-di-AMP pool. Although dltX demonstrated a connection to reverting SpeB expression under an elevated external potassium condition. We also measured c-di-AMP level of 40 clinical isolates of S. pyogenes that are collected from patients suffering from S. pyogenes infections in different sites of the body and analyzed its SpeB and hemolysis activity. Invasive and non-invasive clinical strains showed variable intracellular c-di-AMP level; no discernible association could be identified with the hemolysis and SpeB activity of the clinical isolates.

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