Umbelliferone Impedes Biofilm Formation and Virulence of Methicillin-Resistant Staphylococcus epidermidis via Impairment of Initial Attachment and Intercellular Adhesion

Abstract

Staphylococcus epidermidis is an opportunistic human pathogen, which is involved in numerous nosocomial and implant associated infections. Biofilm formation is one of the prime virulence factors of S. epidermidis that supports its colonization on biotic and abiotic surfaces. The global dissemination of three lineages of S. epidermidis superbugs highlights its clinical significance and the imperative need to combat its pathogenicity. Thus, in the current study, the antibiofilm activity of umbelliferone (UMB), a natural product of the coumarin family, was assessed against methicillin-resistant S. epidermidis (MRSE). UMB exhibited significant antibiofilm activity (83%) at 500 μg/ml concentration without growth alteration. Microscopic analysis corroborated the antibiofilm potential of UMB and unveiled its potential to impair intercellular adhesion, which was reflected in auto-aggregation and solid phase adherence assays. Furthermore, real time PCR analysis revealed the reduced expression of adhesion encoding genes (icaD, atlE, aap, bhp, ebh, sdrG, and sdrF). Down regulation of agrA and reduced production of secreted hydrolases upon UMB treatment were speculated to hinder invasive lifestyle of MRSE. Additionally, UMB hindered slime synthesis and biofilm matrix components, which were believed to augment antibiotic susceptibility. In vivo assays using Caenorhabditis elegans divulged the non-toxic nature of UMB and validated the antibiofilm, antivirulence, and antiadherence properties of UMB observed in in vitro assays. Thus, UMB impairs MRSE biofilm by turning down the initial attachment and intercellular adhesion. Altogether, the obtained results suggest the potent antibiofilm activity of UMB and the feasibility of using it in clinical settings for combating S. epidermidis infections.

Piperine Impedes Biofilm Formation and Hyphal Morphogenesis of Candida albicans

“…For in vivo colonization assessment, worms were crushed in saline and plated on candida differential agar. Internal colonization was also observed under CLSM (Swetha et al, 2019;Valliammai et al, 2019). As this study is intended to evaluate the therapeutic potential of C. albicans for its application in oral candidiasis, safety evaluation was further evaluated with the HBEC.…”

A Natural Alternative Treatment for Urinary Tract Infections: Itxasol©, the Importance of the Formulation

“…Although knowledge of the antibiotic action of UMB is scarce, it has recently been demonstrated that derivates of UMB from plants of genus Ferula are useful against periodontal bacteria, inhibiting bacteria growth and biofilm formation [76]. In agreement with these data, it has been described that UMB can inhibit the formation of the biofilm created by Staphylococcus epidermidis, impairing intracellular adhesion by downregulation in the expressions of genes related to adherence function [77]. The MIC of UMB against different pathogens is shown in Table 4.…”

“…Coumarins downregulate the expression of curli and motility genes, which results in fewer fimbriae and the production of biofilm [ 84 ]. In the same sense, UMB prevents the formation of biofilm by the methicillin-resistant Staphylococcus epidermidis strain at a dose of 500 mg/mL but without affecting the growth of this bacteria [ 77 ].…”

Effects of Itxasol© Components on Gene Expression in Bacteria Related to Infections of the Urinary Tract and to the Inflammation Process

“…This action is carried out by reducing the expression of genes that code for factors involved in the formation of the bacterial biofilm, others that favor bacterial invasion such as agrA , those related to the production of hydrolases, and those of bacterial adhesion such as icaD, atlE, aap, bhp, ebh, sdrG, and sdr . Specifically, Umb is capable of reducing the expression of genes encoding exopolysaccharide (PIA) synthesis icaD , virulence and biofilm formation ( agrA ), intercellular adhesion and accumulation ( aap and bhp ), autolysin/adhesin ( atlE ), and ECM-binding protein ( ebh, sdrG, and sdrF ) [ 59 ]. It is noteworthy that coumarins have an antifungal activity against Candida albicans .…”