Effects of elevated levels of intracellular nitric oxide on Pseudomonas aeruginosa biofilm in chronic skin wound and slow-killing infection models.
Int Microbiol
; 27(2): 349-359, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-37410300
ABSTRACT
Nitric oxide (NO), produced through the denitrification pathway, regulates biofilm dynamics through the quorum sensing system in Pseudomonas aeruginosa. NO stimulates P. aeruginosa biofilm dispersal by enhancing phosphodiesterase activity to decrease cyclic di-GMP levels. In a chronic skin wound model containing a mature biofilm, the gene expression of nirS, encoding nitrite reductase to produce NO, was low, leading to reduced intracellular NO levels. Although low-dose NO induces biofilm dispersion, it is unknown whether it influences the formation of P. aeruginosa biofilms in chronic skin wounds. In this study, a P. aeruginosa PAO1 strain with overexpressed nirS was established to investigate NO effects on P. aeruginosa biofilm formation in an ex vivo chronic skin wound model and unravel the underlying molecular mechanisms. Elevated intracellular NO levels altered the biofilm structure in the wound model by inhibiting the expression of quorum sensing-related genes, which was different from an in vitro model. In Caenorhabditis elegans as a slow-killing infection model, elevated intracellular NO levels increased worms' lifespan by 18%. Worms that fed on the nirS-overexpressed PAO1 strain for 4 h had complete tissue, whereas worms that fed on empty plasmid-containing PAO1 had biofilms on their body, causing severe damage to the head and tail. Thus, elevated intracellular NO levels can inhibit P. aeruginosa biofilm growth in chronic skin wounds and reduce pathogenicity to the host. Targeting NO is a potential approach to control biofilm growth in chronic skin wounds wherein P. aeruginosa biofilms are a persistent problem.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
Limite:
Animals
Idioma:
En
Revista:
Int Microbiol
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China