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Title: Studies on Staphylococcus aureus survival under human colonic conditions
Author: Sannasiddappa, Thippeswamy Hirenallure
ISNI:       0000 0004 5365 0058
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2014
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Although nasal colonisation is a well-established risk factor for most types of Staphylococcal infections, several studies have suggested that intestinal colonisation could have important clinical implications. In this study, the effect of S. aureus infection of the human large intestine on resident microbiota was studied using an in vitro human colonic model system. During infection, S. aureus was able to compromise colonisation resistance by the colonic microbiota thus, transiently decreasing resident bacteria. Furthermore, the concentration of short chain fatty acids in the vessel representing the proximal colon was decreased significantly by infection. Bile salts being potent antimicrobial agents in the human intestine represent major obstacles for the survival and colonisation of invading pathogenic bacteria. Hence, the antimicrobial mode of action of various human bile salts on S. aureus was investigated. Comparatively, unconjugated bile salts were found to be more potent than conjugated bile salts in inhibiting S. aureus growth by membrane damaging effect resulting in dissipation of intracellular pH, transmembrane electric potential, leakage of potassium and probably other ions across the cell membrane and also the low molecular- weight metabolites from the cell. This subsequently leads to loss of proton motive force, important ions, and solutes from the cytoplasm, thereby leading to cell death. However, determined MICs of human bile salts were significantly higher than the physiological levels found in the human intestine, raising the possibility of bile salt resistance in the bacterium. S. aureus components involved in bile salt resistance were identified by mutagenesis and functionally characterized in the heterologous host bacterium. MnhF, an efflux pump was found to be involved in the resistance to unconjugated bile salts. Furthermore, survival of S. aureus 6.mnhF was attenuated compared to wild type in the in vitro human colonic model, implicating MnhF in S. aureus colonisation of the human intestine. Thus, infection by S. aureus appears to be able to alter the overall structure of the human colonic micro biota, the microbial metabolic profiles and resists antimicrobial action of bile salts by efflux.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available