자료유형  

 학위논문

Control Number  

0016933746

International Standard Book Number  

9798380260084

Dewey Decimal Classification Number  

589

Main Entry-Personal Name  

Hurley, Kelly Elizabeth.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pittsburgh., 2022

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2022

Physical Description  

1 online resource(44 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Yasin, Mohamed Hamdy;Mattila, Joshua T.;Richardson, Anthony R.

Dissertation Note  

Thesis (M.Sc.)--University of Pittsburgh, 2022.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Staphylococcus aureus is a major human pathogen that causes a variety of illnesses ranging from minor skin and soft tissue infections (SSTIs) to more severe systemic infections. Although the primary host immune response can typically clear pathogenic bacterial infections, S. aureus is uniquely resistant to this environment. Our lab has determined that nitric oxide (NO), an important component of the innate immune response that plays a role in both immunomodulatory and antibacterial processes, is the effector to which S. aureus is specifically resistant. Additionally, NO and its derivatives can lead to damage of S. aureus DNA, more specifically, deamination and/or oxidation of DNA bases; however, regulation and repair mechanisms of DNA in S. aureus is understudied. Thus, we hypothesize several DNA repair mechanisms may account for the replication fidelity of S. aureus and may contribute to fitness in the presence of NO. Here we show the role of several DNA repair mechanisms in S. aureus. More specifically, we found recombinational repair gene, recG, may play a role in the repair of NO-induced replication fork collapses. We also show a role of base excision repair pathway protein, MutY, in reducing NO- mediated mutagenesis. Lastly, we show the role of the mismatch repair pathway in preventing illegitimate recombination. It is known that MMR proteins prevent RecA-mediated recombination between divergent sequences. S. aureus has three mismatch repair MutS homologues that work alongside an endonuclease, MutL. Only one has been studied and was shown to limit spontaneous mutagenesis but did not appear to have a role in preventing illegitimate homologous recombination. Here we confirm only one MutS homologue, MutS1, contributes to mutagenesis in S. aureus. We also show a role of the MutS1 homologue in preventing illegitimate recombination between divergent sequences. Overall, our results suggest NO leads to DNA damage, which subsequently induces activity of several DNA repair pathways, contributing to the replication fidelity and fitness of S. aureus. Although one mismatch repair homologue contributes to mutagenesis, no other combinatorial homologues play a role.

Subject Added Entry-Topical Term  

Plasmids.

Subject Added Entry-Topical Term  

Nitric oxide.

Subject Added Entry-Topical Term  

Yeast.

Subject Added Entry-Topical Term  

Mutation.

Subject Added Entry-Topical Term  

Staphylococcus infections.

Subject Added Entry-Topical Term  

Pathology.

Added Entry-Corporate Name  

University of Pittsburgh.

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643940