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
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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