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Development of benzo[1,4]oxazines as biofilm inhibitors and dispersal agents against Vibrio cholerae.

Warner CJ, Cheng AT, Yildiz FH, Linington RG - Chem. Commun. (Camb.) (2015)

Bottom Line: Bacterial biofilms are estimated to be associated with over 65 percent of all nosocomial infections.However, no therapeutics have been approved by the FDA which directly mediate biofilm formation or persistence.Herein we report oxazine as a highly potent inhibitor, disperser and in the presence of the appropriate antibiotic eradicator of V. cholerae biofilms.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, California, 95064, USA. rliningt@ucsc.edu.

ABSTRACT
Bacterial biofilms are estimated to be associated with over 65 percent of all nosocomial infections. However, no therapeutics have been approved by the FDA which directly mediate biofilm formation or persistence. Herein we report oxazine as a highly potent inhibitor, disperser and in the presence of the appropriate antibiotic eradicator of V. cholerae biofilms.

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Related in: MedlinePlus

Static and confocal flow cell images of compound 25 against V. cholerae biofilms. (A) static culture conditions, from left to right, DMSO control, compound 25 at 15 μM. In both instances OD600 data suggested no bactericidal activity; (B) confocal flow cell images of V. cholerae, see ESI† for further details. From left to right, DMSO control and lead compound 25 at 250 μM. COMSTAT analysis of mean biomass (mm3/mm2) indicated a 7-fold reduction in the presence of lead compared 25 compared to DMSO control. In both cases white bars indicate 50 μm.
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fig3: Static and confocal flow cell images of compound 25 against V. cholerae biofilms. (A) static culture conditions, from left to right, DMSO control, compound 25 at 15 μM. In both instances OD600 data suggested no bactericidal activity; (B) confocal flow cell images of V. cholerae, see ESI† for further details. From left to right, DMSO control and lead compound 25 at 250 μM. COMSTAT analysis of mean biomass (mm3/mm2) indicated a 7-fold reduction in the presence of lead compared 25 compared to DMSO control. In both cases white bars indicate 50 μm.

Mentions: To examine whether oxazine 25 was capable of disrupting biofilm formation and persistence under more physiologically relevant conditions, we examined its anti-biofilm properties under flow cell conditions. At all concentrations tested (see ESI†), strong biofilm inhibition was observed, with a marked decrease in the size, thickness and morphology of the biofilm. COMSTAT analysis17 indicated a 7-fold reduction in biomass upon treatment of the V. cholerae biofilms with compound 25 under flow conditions (Fig. 3B). These data indicate that compound 25 is capable of disrupting biofilms under both static and flow cell conditions, and suggest that this compound has potential value as a biofilm inhibitor for the clearance of established biofilm-mediated infections in vivo.


Development of benzo[1,4]oxazines as biofilm inhibitors and dispersal agents against Vibrio cholerae.

Warner CJ, Cheng AT, Yildiz FH, Linington RG - Chem. Commun. (Camb.) (2015)

Static and confocal flow cell images of compound 25 against V. cholerae biofilms. (A) static culture conditions, from left to right, DMSO control, compound 25 at 15 μM. In both instances OD600 data suggested no bactericidal activity; (B) confocal flow cell images of V. cholerae, see ESI† for further details. From left to right, DMSO control and lead compound 25 at 250 μM. COMSTAT analysis of mean biomass (mm3/mm2) indicated a 7-fold reduction in the presence of lead compared 25 compared to DMSO control. In both cases white bars indicate 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288701&req=5

fig3: Static and confocal flow cell images of compound 25 against V. cholerae biofilms. (A) static culture conditions, from left to right, DMSO control, compound 25 at 15 μM. In both instances OD600 data suggested no bactericidal activity; (B) confocal flow cell images of V. cholerae, see ESI† for further details. From left to right, DMSO control and lead compound 25 at 250 μM. COMSTAT analysis of mean biomass (mm3/mm2) indicated a 7-fold reduction in the presence of lead compared 25 compared to DMSO control. In both cases white bars indicate 50 μm.
Mentions: To examine whether oxazine 25 was capable of disrupting biofilm formation and persistence under more physiologically relevant conditions, we examined its anti-biofilm properties under flow cell conditions. At all concentrations tested (see ESI†), strong biofilm inhibition was observed, with a marked decrease in the size, thickness and morphology of the biofilm. COMSTAT analysis17 indicated a 7-fold reduction in biomass upon treatment of the V. cholerae biofilms with compound 25 under flow conditions (Fig. 3B). These data indicate that compound 25 is capable of disrupting biofilms under both static and flow cell conditions, and suggest that this compound has potential value as a biofilm inhibitor for the clearance of established biofilm-mediated infections in vivo.

Bottom Line: Bacterial biofilms are estimated to be associated with over 65 percent of all nosocomial infections.However, no therapeutics have been approved by the FDA which directly mediate biofilm formation or persistence.Herein we report oxazine as a highly potent inhibitor, disperser and in the presence of the appropriate antibiotic eradicator of V. cholerae biofilms.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, California, 95064, USA. rliningt@ucsc.edu.

ABSTRACT
Bacterial biofilms are estimated to be associated with over 65 percent of all nosocomial infections. However, no therapeutics have been approved by the FDA which directly mediate biofilm formation or persistence. Herein we report oxazine as a highly potent inhibitor, disperser and in the presence of the appropriate antibiotic eradicator of V. cholerae biofilms.

Show MeSH
Related in: MedlinePlus