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Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

ABSTRACT: Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1) was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.

SUBMITTER: Sanchez LM

PROVIDER: S-EPMC4798295 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

Sanchez Laura M LM Cheng Andrew T AT Warner Christopher J A CJ Townsley Loni L Peach Kelly C KC Navarro Gabriel G Shikuma Nicholas J NJ Bray Walter M WM Riener Romina M RM Yildiz Fitnat H FH Linington Roger G RG

PloS one 20160318 3

Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we ...[more]

PMID: 26992172

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Project description:Biofilms are surface-associated microbial communities known for their increased resistance to antimicrobials and host factors. This resistance introduces a critical clinical challenge, particularly in cases associated with implants increasing the predisposition for bacterial infections. Preventing such infections requires the development of novel antimicrobials or compounds that enhance bactericidal effect of currently available antibiotics. We have synthesized and characterized twelve novel silver(I) cyanoximates designated as Ag(ACO), Ag(BCO), Ag(CCO), Ag(ECO), Ag(PiCO), Ag(PICO) (yellow and red polymorphs), Ag(BIHCO), Ag(BIMCO), Ag(BOCO), Ag(BTCO), Ag(MCO) and Ag(PiPCO). The compounds exhibit a remarkable resistance to high intensity visible light, UV radiation and heat and have poor solubility in water. All these compounds can be well incorporated into the light-curable acrylate polymeric composites that are currently used as dental fillers or adhesives of indwelling medical devices. A range of dry weight % from 0.5 to 5.0 of the compounds was tested in this study. To study the potential of these compounds in preventing planktonic and biofilm growth of bacteria, we selected two human pathogens (Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus) and Gram-positive environmental isolate Bacillus aryabhattai. Both planktonic and biofilm growth was abolished completely in the presence of 0.5% to 5% of the compounds. The most efficient inhibition was shown by Ag(PiCO), Ag(BIHCO) and Ag(BTCO). The inhibition of biofilm growth by Ag(PiCO)-yellow was confirmed by scanning electron microscopy (SEM). Application of Ag(BTCO) and Ag(PiCO)-red in combination with tobramycin, the antibiotic commonly used to treat P. aeruginosa infections, showed a significant synergistic effect. Finally, the inhibitory effect lasted for at least 120 h in P. aeruginosa and 36 h in S. aureus and B. aryabhattai. Overall, several silver(I) cyanoximates complexes efficiently prevent biofilm development of both Gram-negative and Gram-positive bacteria and present a particularly significant potential for applications against P. aeruginosa infections.

Project description:Bacterial biofilms are a major threat to human health, causing persistent infections that lead to millions of fatalities worldwide every year. Biofilms also cause billions of dollars of damage annually by interfering with industrial processes. Recently, cationic pillararenes were found to be potent inhibitors of biofilm formation in Gram-positive bacteria. To identify the structural features of pillararenes that result in antibiofilm activity, we evaluated the activity of 16 cationic pillar[5]arene derivatives including that of the first cationic water-soluble pillar[5]arene-based rotaxane. Twelve of the derivatives were potent inhibitors of biofilm formation by Gram-positive pathogens. Structure activity analyses of our pillararene derivatives indicated that positively charged head groups are critical for the observed antibiofilm activity. Although certain changes in the lipophilicity of the substituents on the positively charged head groups are tolerated, dramatic elevation in the hydrophobicity of the substituents or an increase in steric bulk on these positive charges abolishes the antibiofilm activity. An increase in the overall positive charge from 10 to 20 did not affect the activity significantly, but pillararenes with 5 positive charges and 5 long alkyl chains had reduced activity. Surprisingly, the cavity of the pillar[n]arene is not essential for the observed activity, although the macrocyclic structure of the pillar[n]arene core, which facilitates the clustering of the positive charges, appears important. Interestingly, the compounds found to be efficient inhibitors of biofilm formation were nonhemolytic at concentrations that are ∼100-fold of their MBIC50 (the minimal concentration of a compound at which at least 50% inhibition of biofilm formation was observed compared to untreated cells). The structure-activity relationship guidelines established here pave the way for a rational design of potent cationic pillar[n]arene-based antibiofilm agents.

Dataset Information

Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

Publications

Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

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