The Small Protein CydX Is Required for Cytochrome bd Quinol Oxidase Stability and Function in Salmonella enterica Serovar Typhimurium: a Phenotypic Study
| Autor: | Yoon Mee Park, Bo Gyeong Kang, Kieu Minh Duc, Choa Lee, Iel Soo Bang, Hee Jeong Park, Young Hee Joung |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Salmonella Oxidase test Cytochrome biology 030306 microbiology Mutant biology.organism_classification medicine.disease_cause Microbiology 03 medical and health sciences chemistry.chemical_compound chemistry Salmonella enterica biology.protein medicine Molecular Biology Heme Bacteria Intracellular 030304 developmental biology |
| Zdroj: | Journal of Bacteriology. 202 |
| ISSN: | 1098-5530 0021-9193 |
| DOI: | 10.1128/jb.00348-19 |
| Popis: | Cytochrome bd quinol oxidases, which have a greater affinity for oxygen than heme-copper cytochrome oxidases (HCOs), promote bacterial respiration and fitness in low-oxygen environments, such as host tissues. Here, we show that, in addition to the CydA and CydB subunits, the small protein CydX is required for the assembly and function of the cytochrome bd complex in the enteric pathogen Salmonella enterica serovar Typhimurium. Mutant S Typhimurium lacking CydX showed a loss of proper heme arrangement and impaired oxidase activity comparable to that of a ΔcydABX mutant lacking all cytochrome bd subunits. Moreover, both the ΔcydX mutant and the ΔcydABX mutant showed increased sensitivity to β-mercaptoethanol and nitric oxide (NO). Cytochrome bd-mediated protection from β-mercaptoethanol was not a result of resistance to reducing damage but, rather, was due to cytochrome bd oxidase managing Salmonella respiration, while β-mercaptoethanol interacted with the copper ions necessary for the HCO activity of the cytochrome bo-type quinol oxidase. Interactions between NO and hemes in cytochrome bd and cytochrome bd-dependent respiration during nitrosative stress indicated a direct role for cytochrome bd in mediating Salmonella resistance to NO. Additionally, CydX was required for S Typhimurium proliferation inside macrophages. Mutants deficient in cytochrome bd, however, showed a significant increase in resistance to antibiotics, including aminoglycosides, d-cycloserine, and ampicillin. The essential role of CydX in cytochrome bd assembly and function suggests that targeting this small protein could be a useful antimicrobial strategy, but potential drug tolerance responses should also be considered.IMPORTANCE Cytochrome bd quinol oxidases, which are found only in bacteria, govern the fitness of many facultative anaerobic pathogens by promoting respiration in low-oxygen environments and by conferring resistance to antimicrobial radicals. Thus, cytochrome bd complex assembly and activity are considered potential therapeutic targets. Here we report that the small protein CydX is required for the assembly and function of the cytochrome bd complex in S Typhimurium under stress conditions, including exposure to β-mercaptoethanol, nitric oxide, or the phagocytic intracellular environment, demonstrating its crucial function for Salmonella fitness. However, cytochrome bd inactivation also leads to increased resistance to some antibiotics, so considerable caution should be taken when developing therapeutic strategies targeting the CydX-dependent cytochrome bd. |
| Databáze: | OpenAIRE |
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