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Targeting The Pin Domain Of Type Ii Toxins Is A Novel Approach To Treat Infections Caused By Nontypeable Haemophilus Influenzae, Ashley Lynne Molinaro

Biomedical Sciences Theses & Dissertations

Toxin-antitoxin (TA) gene pairs have been identified in nearly all bacterial genomes sequenced to date and are thought to facilitate persistence and antibiotic tolerance. TA loci are classified into various types based upon the characteristics of their antitoxins, with those in type II expressing proteic antitoxins. Many toxins from type II modules are ribonucleases that maintain a PilT N-terminus (PIN) domain containing conserved amino acids considered essential for activity. The vapBC (virulence associated protein) TA system is the largest subfamily in this class and has been linked to pathogenesis of nontypeable Haemophilus influenzae (NTHi). This dissertation presents three studies investigating …