Characterization of Streptococcus Zinc-Efflux Activator (SczA): A novel transcription factor responsible for metal-ion homeostasis

Tuesday, October 23, 2018


Kayla D. McConnell

Department of Chemistry

Mississippi State University

Abstract

Streptococcus pneumoniae (pneumococcus) can be naturally found in the respiratory tract of asymptomatic individuals. However, in populations with compromised immune systems; such as that of the young, the elderly and persons with diseases that suppress the immune system, pneumococcus can become invasive and life-threatening. The 10 most predominant S. pneumoniae serotypes account for approximately 62% of invasive bacterial disease worldwide, carrying a fatality rate of 8% for children and 22% for adults. In the United States the detection and treatment of streptococcus infection incurred $3.5 billion in medical costs. Antibiotic treatment for those not vaccinated is available, however numerous drug-resistant strains of pneumococcus have been identified, and in 30% of severe S. pneumoniae infections, complete resistance to one or more antibiotics is present. Recent research has been directed toward new avenues for treatment of disease via disrupting biomolecular interactions, specifically metal-dependent transcription factor activity.
Streptococcus zinc-efflux activator (SczA), is a zinc-dependent transcription factor found within Streptococcus strains with the primary responsibility of metal-exportation via the regulation of the cation diffuser facilitator (czcD). In this presentation, I will discuss the proposed mechanism by which SczA accomplishes zinc cellular-efflux as a way to maintain cell homeostasis and prevent rapid apoptosis in streptococci strains. Site directed protein mutagenesis, as well as metal-ion binding studies, including investigating Mn/Zn bioavailability ratio influences, will be discussed. Studies have shown that binding of two zinc ions per protomer and binding at both sites is required for operator sequence recognition and activation of czcD over-expression. Also discussed will be S. pneumoniae overall resistance to zinc toxicity and survival rates in infected human macrophages.

Annotated Bibliography

Characterization of Streptococcus Zinc-Efflux Activator (SczA): A novel transcription factor responsible for metal-ion homeostasis
Kayla D. McConnell

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This article was the locus of SczA related-research. Through DNAse I footprinting, SczA promoter sequences were discovered, as well as the discovery that SczA is both an activator and a repressor of czcD metal-ion efllux from the cell

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            Article published discussing how zinc intoxication is prevented in S. pneumoniae by expression of the zinc exporter CzcD. Through titration studies, it is shown two zinc ions bind per protomer and through mutagenesis analysis, two binding sites with two distinct affinity terms are discovered.

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