Role of RNAIII in Resistance to Antibiotics and Antimicrobial Agents in Staphylococcus epidermidis Biofilms

Abstract

Staphylococcus epidermidis is a known opportunistic pathogen and is one of the leading causes of chronic biofilm-associated infections. Biofilm formation is considered as a main strategy to resist antibiotic treatment and help bacteria escape from the human immune system. Understanding the complex mechanisms in biofilm formation can help find new ways to treat resistant strains and lower the prevalence of nosocomial infections. In order to examine the role of RNAIII regulated by the agr quorum sensing system and to what extent it influences biofilm resistance to antimicrobial agents, deletion mutant S. epidermidis RP62a-ΔRNAIII deficient in repressor domains with a re-maining functional hld gene was created. A deletion strain was used to examine the influence of oxacillin in combination with vanillin on biofilm resistance and cell survival was determined. Utilizing real-time qPCR, confocal laser scanning microscopy (CLSM), and crystal violet staining analyses, we found that the RNAIII-independent controlled phenol soluble modulins (PSMs) and RNAIII effector molecule have a significant role in biofilm resistance to antibiotics and phenolic compounds, and it protects the integrity of biofilms. Moreover, a combination of antibiotic and antimicrobial agents can induce methicillin-resistant S. epidermidis biofilm formation and can lead to exceedingly difficult medical treatment.

Combination antimicrobial therapy: in vitro synergistic effect of anti-staphylococcal drug oxacillin with antimicrobial peptide nisin against Staphylococcus epidermidis clinical isolates and Staphylococcus aureus biofilms

“…Minich et al, found that oxacillin at the 1/2× MIC concentration decreased the relative mRNA expression of icaA in the biofilm-producing strain S. epidermidis RP62A comparison to untreated control ( p < 0.01). In the presence of oxacillin (1/2× MIC) and vanillin (1/20× MIC), icaA expression decreased by 55% ( P < 0.0001), highlighting the advantages of combinatorial strategy in repressing the biofilm determinant genes [ 71 ].…”

Quorum Sensing in Biofilm

“…An important clinical consideration is to determine the strain susceptibility and optimal form of treatment, otherwise, the patient's condition may worsen [102]. In addition, limitations and challenges should be carefully weighed.…”

“…Reportedly, RNAIII inhibitory peptides (RIPs) have shown inhibitory effects on agr and biofilm. It is believed that targeting this molecule will diminish the production of some virulence factors and toxins [101,102]. Similarly, based on the inhibition of agr of another subgroup [103], natural and synthetic AIPs may be introduced as potential inhibitors.…”