Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.7.1.4 (
nitrite reductase
)
1,847
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Biofilm-forming bacteria, including the Gram-negative
Pseudomonas aeruginosa
, cause multiple types of chronic infections and are responsible for serious health burdens in humans, animals, and plants. Nitric oxide (NO) has been shown to induce biofilm dispersal via triggering a reduction in cyclic-di-GMP levels in a variety of bacteria. However, how NO, at homeostatic levels, also facilitates biofilm formation is unknown. Here, we found that complestatin, a structural analog of vancomycin isolated from
Streptomyces
, inhibits
P. aeruginosa
biofilm formation by upregulating NO production via
nitrite reductase
(
NIR
) induction and c-di-GMP degradation via
phosphodiesterase
(
PDE
) stimulation. The complestatin protein target was identified as a nitrite transporter from a genome-wide screen using the Keio
Escherichia coli
knockout library and confirmed using nitrite transporter knockout and overexpression strains. We demonstrated that the nitrite transporter stimulated biofilm formation by controlled NO production via appropriate
NIR
suppression and subsequent diguanylate cyclase (DGC) activation, not
PDE
activity, and c-di-GMP production in
E. coli
and
P. aeruginosa
Thus, this study provides a mechanism for NO-mediated biofilm formation, which was previously not understood.
IMPORTANCE
Bacterial biofilms play roles in infections and avoidance of host defense mechanisms of medically important pathogens and increase the antibiotic resistance of the bacteria. Nitric oxide (NO) is reported to be involved in both biofilm formation and dispersal, which are conflicting processes. The mechanism by which NO regulates biofilm dispersal is relatively understood, but there are no reports about how NO is involved in biofilm formation. Here, by investigating the mechanism by which complestatin inhibits biofilm formation, we describe a novel mechanism for governing biofilm formation in
Escherichia coli
and
Pseudomonas aeruginosa
Nitrite transporter is required for biofilm formation via regulation of NO levels and subsequent c-di-GMP production. Additionally, the nitrite transporter contributes more to
P. aeruginosa
virulence than quorum sensing. Thus, this study identifies nitrite transporters as new antibiofilm targets for future practical and therapeutic agent development.
...
PMID:The Nitrite Transporter Facilitates Biofilm Formation via Suppression of Nitrite Reductase and Is a New Antibiofilm Target in Pseudomonas aeruginosa. 3263 43
