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Identification of a Small Molecule Anti-biofilm Agent Against Salmonella enterica
Biofilm formation is a common strategy utilized by bacterial pathogens to establish persistence in a host niche. serovar Typhi, the etiological agent of Typhoid fever, relies on biofilm formation in the gallbladder to chronically colonize asymptomatic carriers, allowing for transmission to uninfecte...
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Published in: | Frontiers in microbiology 2018-11, Vol.9, p.2804-2804 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Biofilm formation is a common strategy utilized by bacterial pathogens to establish persistence in a host niche.
serovar Typhi, the etiological agent of Typhoid fever, relies on biofilm formation in the gallbladder to chronically colonize asymptomatic carriers, allowing for transmission to uninfected individuals.
serovar Typhimurium utilizes biofilms to achieve persistence in human and animal hosts, an issue of both clinical and agricultural importance. Here, we identify a compound that selectively inhibits biofilm formation in both
Typhi and
Typhimurium serovars at early stages of biofilm development with an EC
of 21.0 and 7.4 μM, respectively. We find that this compound, T315, also reduces biofilm formation in
, a nosocomial and opportunistic pathogen with rising antibiotic resistance. T315 treatment in conjunction with sub-MIC dosing of ciprofloxacin further reduces
biofilm formation, demonstrating the potential of such combination therapies for therapeutic development. Through synthesis of two biotin-labeled T315 probes and subsequent pull-down and proteomics analysis, we identified a T315 binding target: WrbA, a flavin mononucleotide-dependent NADH:quinone oxidoreductase. Using a
Typhimurium strain lacking WrbA we demonstrate that this factor contributes to endogenous
biofilm formation processes and is required for full T315 anti-biofilm activity. We suggest WrbA as a promising target for further development of anti-biofilm agents in
, with potential for use against additional bacterial pathogens. The development of anti-biofilm therapeutics will be essential to combat chronic carriage of Typhoid fever and thus accomplish a meaningful reduction of global disease burden. |
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ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2018.02804 |