The anti-sigma factor MucA of Pseudomonas aeruginosa: Dramatic differences of a mucA22 vs. a ΔmucA mutant in anaerobic acidified nitrite sensitivity of planktonic and biofilm bacteria in vitro and during chronic murine lung infection
Autor: | Daniel A. Muruve, Long J. Lu, Dennis E. Ohman, Boo Shan Tseng, Gee W. Lau, Ralph J. Panos, Michael J. Schurr, Shengchang Su, Daniel J. Hassett, Thomas B. Thompson, Hongwei D. Yu, Warunya Panmanee, Cameron T. McDaniel, Xiaoting Zhu, Zhaowei Ren |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Pulmonology Microarrays Mutant Gene Expression ATP-binding cassette transporter medicine.disease_cause Sigma factor Medicine and Health Sciences Pathogen Lung Multidisciplinary biology Chemistry respiratory system Hydrogen-Ion Concentration Plankton 3. Good health Bioassays and Physiological Analysis Pseudomonas aeruginosa Medicine Research Article Science Chronic Obstructive Pulmonary Disease 030106 microbiology Anaerobic Bacteria Research and Analysis Methods Microbiology 03 medical and health sciences Bacterial Proteins Gene Types medicine Genetics Humans Pseudomonas Infections Gene Regulation Nitrites Bacteria Biofilm Organisms Biology and Life Sciences Bacteriology biology.organism_classification respiratory tract diseases Quorum sensing 030104 developmental biology Biofilms Chronic Disease Mutation Respiratory Infections Regulator Genes Bacterial Biofilms |
Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 6, p e0216401 (2019) |
ISSN: | 1932-6203 |
Popis: | Mucoid mucA22 Pseudomonas aeruginosa (PA) is an opportunistic lung pathogen of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients that is highly sensitive to acidified nitrite (A-NO2-). In this study, we first screened PA mutant strains for sensitivity or resistance to 20 mM A-NO2- under anaerobic conditions that represent the chronic stages of the aforementioned diseases. Mutants found to be sensitive to A-NO2- included PA0964 (pmpR, PQS biosynthesis), PA4455 (probable ABC transporter permease), katA (major catalase, KatA) and rhlR (quorum sensing regulator). In contrast, mutants lacking PA0450 (a putative phosphate transporter) and PA1505 (moaA2) were A-NO2- resistant. However, we were puzzled when we discovered that mucA22 mutant bacteria, a frequently isolated mucA allele in CF and to a lesser extent COPD, were more sensitive to A-NO2- than a truncated ΔmucA deletion (Δ157-194) mutant in planktonic and biofilm culture, as well as during a chronic murine lung infection. Subsequent transcriptional profiling of anaerobic, A-NO2--treated bacteria revealed restoration of near wild-type transcript levels of protective NO2- and nitric oxide (NO) reductase (nirS and norCB, respectively) in the ΔmucA mutant in contrast to extremely low levels in the A-NO2--sensitive mucA22 mutant. Proteins that were S-nitrosylated by NO derived from A-NO2- reduction in the sensitive mucA22 strain were those involved in anaerobic respiration (NirQ, NirS), pyruvate fermentation (UspK), global gene regulation (Vfr), the TCA cycle (succinate dehydrogenase, SdhB) and several double mutants were even more sensitive to A-NO2-. Bioinformatic-based data point to future studies designed to elucidate potential cellular binding partners for MucA and MucA22. Given that A-NO2- is a potentially viable treatment strategy to combat PA and other infections, this study offers novel developments as to how clinicians might better treat problematic PA infections in COPD and CF airway diseases. |
Databáze: | OpenAIRE |
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