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Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.

ABSTRACT: Pseudomonas aeruginosa is the major pathogenic bacteria in cystic fibrosis and other forms of bronchiectasis. Growth in antibiotic-resistant biofilms contributes to the virulence of this organism. Sodium nitrite has antimicrobial properties and has been tolerated as a nebulized compound at high concentrations in human subjects with pulmonary hypertension; however, its effects have not been evaluated on biotic biofilms or in combination with other clinically useful antibiotics. We grew P. aeruginosa on the apical surface of primary human airway epithelial cells to test the efficacy of sodium nitrite against biotic biofilms. Nitrite alone prevented 99% of biofilm growth. We then identified significant cooperative interactions between nitrite and polymyxins. For P. aeruginosa growing on primary CF airway cells, combining nitrite and colistimethate resulted in an additional log of bacterial inhibition compared to treating with either agent alone. Nitrite and colistimethate additively inhibited oxygen consumption by P. aeruginosa. Surprisingly, whereas the antimicrobial effects of nitrite in planktonic, aerated cultures are nitric oxide (NO) dependent, antimicrobial effects under other growth conditions are not. The inhibitory effect of nitrite on bacterial oxygen consumption and biofilm growth did not require NO as an intermediate as chemically scavenging NO did not block growth inhibition. These data suggest an NO-radical independent nitrosative or oxidative inhibition of respiration. The combination of nebulized sodium nitrite and colistimethate may provide a novel therapy for chronic P. aeruginosa airway infections, because sodium nitrite, unlike other antibiotic respiratory chain "poisons," can be safely nebulized at high concentration in humans.

SUBMITTER: Zemke AC

PROVIDER: S-EPMC4278422 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.

Zemke Anna C AC Shiva Sruti S Burns Jane L JL Moskowitz Samuel M SM Pilewski Joseph M JM Gladwin Mark T MT Bomberger Jennifer M JM

Free radical biology & medicine 20140916

Pseudomonas aeruginosa is the major pathogenic bacteria in cystic fibrosis and other forms of bronchiectasis. Growth in antibiotic-resistant biofilms contributes to the virulence of this organism. Sodium nitrite has antimicrobial properties and has been tolerated as a nebulized compound at high concentrations in human subjects with pulmonary hypertension; however, its effects have not been evaluated on biotic biofilms or in combination with other clinically useful antibiotics. We grew P. aerugin ...[more]

PMID: 25229185

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Project description:Enterococci are commonly found in humans, animals and environments. Their highly adaptive mechanisms are related to several virulent determinants and their ability to resist antibiotics. Data on the relationship between the esp gene, biofilm formation and antibiotic susceptibility profiles may differ between countries. This cross-sectional study was conducted to determine the proportion of esp gene and biofilm formation among Enterococcus faecalis and Enterococcus faecium clinical isolates. We also investigated the possible association between the esp gene with antibiotic susceptibility patterns and biofilm formation. The isolates were collected from clinical samples and identified using biochemical tests and 16SRNA. Antibiotic susceptibility patterns and a biofilm assay were conducted according to the established guidelines. Molecular detection by PCR was used to identify the esp gene using established primers. In total, 52 and 28 of E. faecalis and E. faecium were identified, respectively. E. faecium exhibited higher resistance rates compared to E. faecalis as follows: piperacillin/tazobactam (100% versus 1.9%), ampicillin (92.8% versus 1.9%), high-level gentamicin resistance (HLGR) (89.3% versus 25.0%) and penicillin (82.1% versus 7.7%). E. faecium produced more biofilms than E. faecalis (59.3% versus 49.0%). E. faecium acquired the esp gene more frequently than E. faecalis (78.6% versus 46.2%). Interestingly, the associations between ampicillin and tazobactam/piperacillin resistance with the esp gene were statistically significant (X2 = 4.581, p = 0.027; and X2 = 6.276, p = 0.012, respectively). Our results demonstrate that E. faecium exhibits high rates of antimicrobial resistance, esp gene acquisition and biofilm formation. These peculiar traits of E. faecium may have implications for the management of enterococcal infections in hospitals. Thus, concerted efforts by all parties in establishing appropriate treatment and effective control measures are warranted in future.

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Dataset Information

Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.

Publications

Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.

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