Mycobacterium smegmatis RoxY Is a Repressor of oxyS and Contributes to Resistance to Oxidative Stress and Bactericidal Ubiquitin-Derived Peptides ▿ †
Autor: | Aaron Daugherty, Georgiana E. Purdy, Katelyn M. Powers, Melissa Standley, Cathy S. Kim |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Transposable element
Antimicrobial peptides Mutant Mycobacterium smegmatis Repressor Down-Regulation Microbiology Bacterial Proteins Lysosome Drug Resistance Bacterial Transcriptional regulation medicine Molecular Biology Gene Molecular Biology of Pathogens biology Ubiquitin Gene Expression Regulation Bacterial biology.organism_classification Anti-Bacterial Agents Repressor Proteins Oxidative Stress medicine.anatomical_structure Biochemistry Peptides |
Popis: | The mycobactericidal properties of macrophages include the generation of reactive oxygen intermediates and the delivery of bacteria to a hydrolytic lysosome enriched in bactericidal ubiquitin-derived peptides (Ub-peptides). To better understand the interactions of ubiquitin-derived peptides with mycobacteria and identify putative mycobacterial intrinsic resistance mechanisms, we screened for transposon mutants with increased susceptibility to the bactericidal Ub-peptide Ub2. We isolated 27 Mycobacterium smegmatis mutants that were hypersusceptible to Ub2. Two mutants were isolated that possessed mutations in the msmeg _ 0166 gene, which encodes a transcriptional regulator. The msmeg _ 0166 mutants were also hypersusceptible to other host antimicrobial peptides and oxidative stress. In characterizing msmeg _ 0166 , we found that it encodes a r epressor of oxy S , and therefore we have renamed the gene roxY . We demonstrate that RoxY and OxyS contribute to M. smegmatis resistance to oxidative stress. An ahpD transposon mutant was also isolated in our screen for Ub-peptide hypersusceptibility. Overexpression of oxyS in M. smegmatis reduced transcription of the ahpCD genes, which encode a peroxide detoxification system. Our data indicate that RoxY, OxyS, and AhpD play a role in the mycobacterial oxidative stress response and are important for resistance to host antimicrobial peptides. |
Databáze: | OpenAIRE |
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