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Nanoemulsion-loaded hydrogel coatings for inhibition of bacterial virulence and biofilm formation on solid surfaces.

ABSTRACT: The indiscriminate use of antibiotics has led to the emergence of drug-resistant bacteria which has become one of the biggest challenges of the twenty-first century for the researchers to combat and in turn search for novel targets which could lead to the development of effective and sustainable therapies. Inhibition of biofilm formation and virulence of bacterial pathogens is an emerging approach to address the challenges related to bacterial infections. To suppress the virulence and biofilm formation by Escherichia coli O157:H7 (ECOH), we developed stable nanoemulsion (NE) of Gaultheria fragrantissima Wall. essential oil's (EO) bioactive compounds, viz., eugenol (E-NE) and methyl salicylate (MS-NE) that showed significantly higher anti-biofilm and anti-virulence activities as compared to eugenol and methyl salicylate without affecting ECOH planktonic cell growth. Transcriptional analysis showed that E-NE and MS-NE reduced the expression of genes, including curli, type I fimbriae, Shiga-like toxins, quorum sensing, and ler-controlled toxins, which are needed for biofilm formation, pathogenicity, and attachment. E-NE and MS-NE loaded hydrogel coatings showed superior anti-biofilm activity against ECOH on glass, plastic and meat surfaces as compared to eugenol and methyl salicylate loaded coatings. Conclusively, NE-loaded hydrogel coatings could be used in combating ECOH infection on solid surfaces through anti-biofilm and anti-virulence strategies.

SUBMITTER: Prateeksha

PROVIDER: S-EPMC6482171 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Nanoemulsion-loaded hydrogel coatings for inhibition of bacterial virulence and biofilm formation on solid surfaces.

Prateeksha Barik Saroj Kanta SK Singh Brahma Nand BN

Scientific reports 20190424 1

The indiscriminate use of antibiotics has led to the emergence of drug-resistant bacteria which has become one of the biggest challenges of the twenty-first century for the researchers to combat and in turn search for novel targets which could lead to the development of effective and sustainable therapies. Inhibition of biofilm formation and virulence of bacterial pathogens is an emerging approach to address the challenges related to bacterial infections. To suppress the virulence and biofilm fo ...[more]

PMID: 31019240

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Project description:Intestinal disease or surgical intervention results in local changes in tissue and host-derived factors triggering bacterial virulence. A key phenotype involved in impaired tissue healing is increased bacterial collagenase expression which degrades intestinal collagen. Antibiotic administration is ineffective in addressing this issue as it inadvertently eliminates normal flora while allowing pathogenic bacteria to "bloom" and acquire antibiotic resistance. Compounds that could attenuate collagenase production while allowing commensal bacteria to proliferate normally would offer major advantages without the risk of the emergence of resistance. We have previously shown that intestinal phosphate depletion in the surgically stressed host is a major cue that triggers P. aeruginosa virulence which is suppressed under phosphate abundant conditions. Recent findings indicate that orally administered polyphosphate, hexametaphosphate, (PPi) suppresses collagenase, and biofilm production of P. aeruginosa and S. marcescens in animal models of intestinal injury but does not attenuate E. faecalis induced collagenolytic activity (Hyoju et al., 2017). Systemic administration of phosphates, however, is susceptible to rapid clearance. Given the diversity of collagenase producing bacteria and the variation of phosphate metabolism among microbial species, a combination therapy involving different phosphate compounds may be required to attenuate pathogenic phenotypes. To address these barriers, we present a drug delivery approach for sustained release of phosphates from poly(ethylene) glycol (PEG) hydrogel nanoparticles. The efficacy of monophosphate (Pi)- and PPi-loaded NPs (NP-Pi and NP-PPi, respectively) and a combination treatment (NP-Pi + NP-PPi) in mitigating collagenase and biofilm production of gram-positive and gram-negative pathogens expressing high collagenolytic activity was investigated. NP-PPi was found to significantly decrease collagenase and biofilm production of S. marcescens and P. aeruginosa. Treatment with either NP-Pi or NP-Pi + NP-PPi resulted in more prominent decreases in E. faecalis collagenase compared to NP-PPi alone. The combination treatment was also found to significantly reduce P. aeruginosa collagenase production. Finally, significant attenuation in biofilm dispersal was observed with NP-PPi or NP-Pi + NP-PPi treatment across all test pathogens. These findings suggest that sustained release of different forms of phosphate confers protection against gram-positive and gram-negative pathogens, thereby providing a promising treatment to attenuate expression of tissue-disruptive bacterial phenotypes without eradicating protective flora over the course of intestinal healing.

Project description:ObjectivesThe present study aimed to evaluate the potential of the salivary pellicle (SP) formed on titanium (Ti) surfaces to modulate the formation of a biofilm composed of Streptococcus gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis.Materials and methodsTi substrates were incubated for 2 h with a pool of saliva samples obtained from 10 systemically and periodontally healthy subjects. Enamel substrates were included as a biological reference. Scanning electron microscopy (SEM) and Raman spectroscopy analysis were used to analyze the formation of the salivary pellicle. After the SP formation, the surfaces were incubated for 12 h with a mix of Streptococcus gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis. The number of bacterial cells attached to each surface was determined by the XTT assay while bacterial viability was analyzed by fluorescence microscopy using the LIVE/DEAD® BacLightTM kit.ResultsThe SEM and Raman spectroscopy analysis confirmed the presence of a salivary pellicle formed on the tested surfaces. Regarding the biofilm formation, the presence of the SP decreases the number of the bacterial cells detected in the test surfaces, compared with the uncover substrates. Even more, the SP-covered substrates showed similar bacterial counts in both Ti and enamel surfaces, meaning that the physicochemical differences of the substrates were less determinant than the presence of the SP. While on the SP-uncover substrates, differences in the bacterial adhesion patterns were directly related to the physicochemical nature of the substrates.ConclusionsThe salivary pellicle was the main modulator in the development of the biofilm consisting of representative oral bacteria on the Ti substrates.Clinical relevanceThe results of this study provide valuable information on the modulatory effect of the salivary pellicle on biofilm formation; such information allows us to understand better the events involved in the formation of oral biofilms on Ti dental implants.

Project description:Background & aimsAltered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT).MethodsVF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups.ConclusionsVirulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis.PresentationsPortions of this manuscript were an oral presentation in the virtual International Liver Congress 2021.AbbreviationsVF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injury.

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Nanoemulsion-loaded hydrogel coatings for inhibition of bacterial virulence and biofilm formation on solid surfaces.

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Nanoemulsion-loaded hydrogel coatings for inhibition of bacterial virulence and biofilm formation on solid surfaces.

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