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dc.contributor.authorStewart, Philip S.
dc.contributor.authorFranklin, Michael J.
dc.contributor.authorFolsom, James P.
dc.contributor.authorBoegli, Laura
dc.contributor.authorJames, Garth A.
dc.identifier.citationStewart, Philip S., Michael J. Franklin, James P. Folsom, Laura Boegli, and Garth A. James. "Contribution of Stress Responses to Antibiotic Tolerance in Pseudomonas aeruginosa Biofilms ." Antimicrobial Agents and Chemotherapy 59, no. 7 (April 2015): 3838-3847. DOI: .en_US
dc.description.abstractEnhanced tolerance of biofilm-associated bacteria to antibiotic treatments is likely due to a combination of factors, including changes in cell physiology as bacteria adapt to biofilm growth and the inherent physiological heterogeneity of biofilm bacteria. In this study, a transcriptomics approach was used to identify genes differentially expressed during biofilm growth of Pseudomonas aeruginosa. These genes were tested for statistically significant overlap, with independently compiled gene lists corresponding to stress responses and other putative antibiotic-protective mechanisms. Among the gene groups tested were those associated with biofilm response to tobramycin or ciprofloxacin, drug efflux pumps, acyl homoserine lactone quorum sensing, osmotic shock, heat shock, hypoxia stress, and stationary-phase growth. Regulons associated with Anr-mediated hypoxia stress, RpoS-regulated stationary-phase growth, and osmotic stress were significantly enriched in the set of genes induced in the biofilm. Mutant strains deficient in rpoS, relA and spoT, or anr were cultured in biofilms and challenged with ciprofloxacin and tobramycin. When challenged with ciprofloxacin, the mutant strain biofilms had 2.4- to 2.9-log reductions in viable cells compared to a 0.9-log reduction of the wild-type strain. Interestingly, none of the mutants exhibited a statistically significant alteration in tobramycin susceptibility compared to that with the wild-type biofilm. These results are consistent with a model in which multiple genes controlled by overlapping starvation or stress responses contribute to the protection of a P. aeruginosa biofilm from ciprofloxacin. A distinct and as yet undiscovered mechanism protects the biofilm bacteria from tobramycin.en_US
dc.description.sponsorshipNIH/NIAID award AI113330; NIH/NIGMS award GM109452en_US
dc.titleContribution of Stress Responses to Antibiotic Tolerance in Pseudomonas aeruginosa Biofilmsen_US
mus.citation.journaltitleAntimicrobial Agents and Chemotherapyen_US
mus.identifier.categoryEngineering & Computer Scienceen_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Engineeringen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentCenter for Biofilm Engineering.en_US
mus.relation.departmentChemical & Biological Engineering.en_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.contributor.orcidStewart, Philip S.|0000-0001-7773-8570en_US
mus.contributor.orcidFolsom, James P.|0000-0002-4586-4086en_US

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