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Role of copper homeostasis in the pathogenesis of Streptococcus pyogenes
Dao, Tina hong
Dao, Tina hong
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Biology, Department of, Honors papers, Student research
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Abstract
Metals serve as cofactors of many crucial proteins in various cellular processes. Copper, in particular, not only is an essential trace element found in all eukaryotes and some prokaryotes, but it also has antimicrobial properties. The mammalian host exploits copper’s antimicrobial properties to kill bacteria during the innate immune response. Copper efflux mechanisms have been highly conserved in bacterial systems to minimize toxicity. Previous studies have shown that deletion of the copper exporter gene copA in Streptococcus pneumoniae resulted in hypersensitivity to elevated intracellular copper. Streptoccocus pneumoniae and Streptococcus pyogenes share many similarities such as the ability to cause pneumonia and bacteremia and lyse blood cells. Currently, there are no published studies on the role of the copper efflux pump and the mechanism of copper-mediated toxicity in S. pyogenes. In this study, an in-frame deletion in copA (SPy_1715) was constructed in the S. pyogenes HSC5 wild-type strain. This mutant, named ΔcopA, universally showed increased sensitivity to copper compared to the wild type. Virulence of the ΔcopA mutant was attenuated. The mutant developed significantly smaller lesions 24- and 48-hours post-infection in SKH1 hairless mice. The upregulation of czcD, which encodes a zinc exporter, under copper stress suggests that there is crosstalk between the copper and zinc efflux systems. Data presented here on the role of the S. pyogenes copper efflux system in virulence and metal homeostasis will be beneficial in developing future therapeutic strategies to reduce streptococcal infections.
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Permission to publish this honors paper was granted by the author and submitted on a CD.