YpdA, a putative bacillithiol disulfide reductase, contributes to cellular redox homeostasis and virulence in Staphylococcus aureus
| Autor: | George Y. Liu, Irina V. Mikheyeva, Nadia Gaϊa, Anna-Rita Corvaglia, Mamta Rawat, Patrice Francois, Stefano Leo, Ambrose L. Cheung, Stacey L. Kolar, Jason M. Thomas |
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| Rok vydání: | 2018 |
| Předmět: |
Staphylococcus aureus
Neutrophils Mutant Reductase Biology medicine.disease_cause Microbiology Article 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins medicine Homeostasis Humans Molecular Biology Cells Cultured 030304 developmental biology ddc:616 0303 health sciences Virulence 030306 microbiology Wild type Cytosol Bacillithiol chemistry Biochemistry Mutation NAD+ kinase Oxidation-Reduction Protein Kinases Oxidative stress Intracellular |
| Zdroj: | Molecular Microbiology, Vol. 111, No 4 (2019) pp. 1039-1056 |
| ISSN: | 1365-2958 0950-382X |
| Popis: | The intracellular redox environment of Staphylococcus aureus is mainly buffered by bacillithiol (BSH), a low molecular weight thiol. The identity of enzymes responsible for the recycling of oxidized bacillithiol disulfide (BSSB) to the reduced form (BSH) remains elusive. We examined YpdA, a putative bacillithiol reductase, for its role in maintaining intracellular redox homeostasis. The ypdA mutant showed increased levels of BSSB and a lower bacillithiol redox ratio vs. the isogenic parent, indicating a higher level of oxidative stress within the bacterial cytosol. We showed that YpdA consumed NAD(P)H; and YpdA protein levels were augmented in response to stress. Wild type strains overexpressing YpdA showed increased tolerance to oxidants and electrophilic agents. Importantly, YpdA overexpression in the parental strain caused an increase in BSH levels accompanied by a decrease in BSSB concentration in the presence of stress, resulting in an increase in bacillithiol redox ratio vs. the vector control. Additionally, the ypdA mutant exhibited decreased survival in human neutrophils (PMNs) as compared with the parent, while YpdA overexpression protected the resulting strain from oxidative stress in vitro and from killing by human neutrophils ex vivo. Taken together, these data present a new role for YpdA in Staphylococcus aureus physiology and virulence through the bacillithiol system. |
| Databáze: | OpenAIRE |
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