Date of Award


Degree Type


Degree Name

Master of Science


Microbiology and Immunology


Dr. David Heinrichs

Second Advisor

Dr. John McCormick

Third Advisor

Dr. Martin McGavin


Staphylococcus aureus is a notorious, Gram-positive, coccoid-shaped bacterium that is pathogenic to humans and animals. It is the culprit of many infectious diseases ranging from boils, impetigo, and food poisoning to more serious diseases such as endocarditis, osteomyelitis,‘ and toxic shock syndrome. However, for S. aureus to survive in the host, nutrients and especially iron must be acquired. S. aureus expresses iron-regulated surface determinant (Isd) proteins that, together, function in the acquisition of heme iron. However, mutants devoid of IsdA or IsdE have only subtle defects in growth on heme as a sole iro» source. Here I demonstrate that an isd locus deletion mutant (Aisd) grows better than wildtype on heme-containing media, indicating the existence of non-isd mechanisms of heme acquisition. Transposon mutagenesis in the A isd background identified an insertion in brnQ3, encoding a putative branched chain amino acid (BCAA) transporter, which yielded a strain that grew extremely poorly, with an extended lag period, on media containing heme as a sole iron source. Expression of either brnQ3 or isdEF in trans, or exogenously supplying a mixture of Ile/Leu/Val/Thr complemented the growth deficiency of the mutant. In comparison to wildtype S. aureus, the isd brnQ3 mutant had impaired virulence in mice. Together, the data show not only that isdEF is active in heme uptake but also suggest tha' brnQ3, despite the presence of two additional paralogs, is important for uptake of BCAAs, and that intracellular BCAAs, which are an indicator of nutritional status, regulate expression of an alternate, non-Isd, heme uptake mechanism in S. aureus.



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