Journal
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Volume 128, Issue -, Pages 50-58Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2022.08.001
Keywords
Nitric oxide; Pseudomonas aeruginosa; Alginate biosynthesis
Categories
Funding
- Shaanxi Academy of Sciences Project [2018nk-01]
- Foundation of Science and Technology in Shaanxi Province [2020TD-050]
- National Key R D Program [2017YFA0504000]
- National Natural Science Foundation of China [91849203, 31900893]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB39000000]
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The study found that nitric oxide can significantly reduce the expression of algU in Pseudomonas aeruginosa, thereby inhibiting the synthesis of alginate. This inhibitory effect was observed in nine clinical PA isolates, especially in mucoid strains.
In the process of chronic cystic fibrosis (CF) infection, Pseudomonas aeruginosa (PA) is converted into a mucoid phenotype characterized by an overproduction of exopolysaccharide alginate. The alginate forms a thick mucus that causes difficulty in patient's breathing, drug resistance and contributes to both the morbidity and mortality of the patient. AlgU of PA, an extracytoplasmic function sigma factor, is responsible for the alginate over-production and leads to mucoidy and chronic infection of CF patients. In this report, we found that endogenous and exogenous nitric oxide (NO) can significantly reduce algU expression, leading to down-regulation of a series of alginate synthesis-related genes (algD, alg8, algX, and algK), eventually down-regulated alginate synthesis. A fluorescent reporter strain was constructed to clarify the inhibitory effect of alginate synthesis through real-time monitoring in different conditions. The results showed that NO presented inhibitory effect on alginate synthesis in nine clinical PA isolates as in the PA reference strain, and the reduction of alginate was more significant in three mucoid strains (by about 51%, 70% and 61%, respectively, while 47% for the reference strain). In the co -culture system, effect of NO on PA fluorescence intensity is similar to that in monocultures, with the best effect at 10 mu M NO donor sodium nitroprusside (SNP). Finally, we examined the changes in the antibiotic susceptibility of PA under NO-inhibited alginate conditions. In the presence of 10 mu M SNP, the number of planktonic cells increased, and both adherent and planktonic PA cells showed increased susceptibility to tobramycin. We thus suggest that NO can potentially be employed as a therapeutic strategy to prevent cystic fibrosis lungs from PA infection.
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