All ETDs from UAB

Advisory Committee Chair

Champion Deivanayagam

Advisory Committee Members

Suzanne Michalek

Hui Wu

Todd Green

Chad Petit

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Streptococci are involved in the infections of the oral cavity as well as at various sites throughout the body. Their initial contact with tissues/surfaces is enabled by adhesins present on the microbial surface. Among these the Antigen I/II- family (AgI/II) of adhesins are known be important factors in these infections as they enable adherence to multiple host proteins thus allowing the bacteria to gain a foot hold. In this thesis, we have structurally and functionally characterized yet another adhesin on S. mutans, the glucan binding protein C, which resembles the V-region of AgI/II. In addition, we have also resolved the structure of Pas of S. intermedius, another AgI/II-family of proteins, and investigated its adherence to Glycoprotein 340 (Gp340) and the blood protein fibrinogen. Additionally, we characterized the potential role of Pas in enabling biofilm formation with opportunistic pathogens Candida albicans and Pseudomonas aeruginosa. A more extensive functional repertoire for AgI/II-family proteins is becoming apparent. Beyond nanomolar adherence to tooth surface bound Gp340, they target other host proteins for adherence, and are involved in interkingdom interactions not only in the oral cavity but also lung alveoli. The following results are presented in this dissertation:1. We report the high-resolution structure (1.14 Å) of the GbpC protein showing a lectin-like fold with a short stalk. The affinity of GbpC to dextran was biophysically characterized using isothermal titration calorimetry (ITC). A cocrystal structure of GbpC with glucose is also presented which was used to model GpbC’s potential interaction with glucans (dextran). In addition, we describe a newly discovered function, where GpbC adheres to Gp340/SRCR, and expose that GbpC belongs to both the sucrose-dependent and independent class of adhesins on S. mutans. 2. We have determined the crystal structures of the apical lectin-like fold (1.7 Å), as well as the three C-terminal DEv-IgG folds (2.7 Å) of Streptococcus intermedius AgI/II equivalent protein Pas. Their adherence to Gp340/SRCR and the fibrinogen were characterized using surface plasmon resonance. Through biofilm studies, we established that Pas mediates interactions with opportunistic pathogens Candida albicans and Pseudomonas aeruginosa, which are the known to exacerbate cystic fibrosis lungs.



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