An Overview of the Factors Involved in Biofilm Production by the Enterococcus Genus

Review An Overview of the Factors Involved in Biofilm Production by the Enterococcus Genus

Abstract: Enterococcus species are known for their ability to form biofilms, which contributes to their survival in extreme environments and involvement in persistent bacterial infections, especially in the case of multi-drug-resistant strains. This review aims to provide a comprehensive understanding of the mechanisms underlying biofilm formation in clinically important species such as Enterococcus faecalis and the less studied but increasingly multi-drug-resistant Enterococcus faecium, and explores potential strategies for their eradication. Biofilm formation in Enterococcus involves a complex interplay of genes and virulence factors, including gelatinase, cytolysin, Secreted antigen A, pili, microbial surface components that recognize adhesive matrix molecules, and DNA release. Quorum sensing, a process of intercellular communication, mediated by peptide pheromones such as Cob, Ccf, and Cpd, plays a crucial role in coordinating biofilm development by targeting gene expression and regulation. Additionally, the regulation of extracellular DNA release has emerged as a fundamental component in biofilm formation. In E. faecalis, the autolysin N-acetylglucosaminidase and proteases such as gelatinase and serin protease are key players in this process, influencing biofilm development and virulence. Targeting extracellular DNA may offer a promising avenue for intervention in biofilm-producing E. faecalis infections. Overall, gaining insights into the intricate mechanisms of biofilm formation in Enterococcus may provide directions for anti-biofilm therapeutic research, with the purpose of reducing the burden of Enterococcus-associated infections.

One. Introduction

As an opportunistic pathogen, the Enterococcus genus is notorious for its ability to form biofilms. Enterococcal species are common in clinical settings, being responsible for fourteen point seven percent of healthcare-associated infections in adults. They are frequently resistant to multiple commonly used antibiotics, including vancomycin. Enterococcal biofilms have been detected in a variety of infections, such as periodontal, wound and urinary tract infections, as well as on medical devices such as ureteral stents and intravascular catheters. While not traditionally considered a respiratory pathogen, Enterococcus faecalis has been detected in lower respiratory tract infections and has been shown to form biofilms on endotracheal tubes.

Enterococcus faecium is another clinically important species that frequently causes healthcare-associated infections, such as urinary tract infections and bacteremia, with frequent multi-drug resistance, and particularly concerning-and increasing-vancomycin resistance.

The Enterococcus genus also includes a wide variety of species besides Enterococcus faecalis and Enterococcus faecium, which are gathered in a group called non-faecalis non-faecium Enterococcus or Other Enterococcus. The Other Enterococcus group also can be classified into vanC-positive Other Enterococcus (including Enterococcus gallinarum and Enterococcus casseliflavus) and vanC-negative Other Enterococcus (the other species). Although the vanC-positive species have a high clinical relevance due to the presence of an intrinsic resistance to glycopeptides, via the vanC gene, their involvement in biofilm formation has not been extensively studied so far. Also, the vanC-negative Other Enterococcus remains a rare encounter in the clinic setting. However, recent studies have highlighted that, for some species like Enterococcus avium, Enterococcus durans and Enterococcus raffinosus, there might be a site-specific association; however, a definitive conclusion has not yet been made and their involvement in biofilm formation has also not been widely described.

The process called biofilm formation comprises four stages: Initial attachment, microcolony formation (in part correlated with quorum sensing), biofilm maturation and dispersal. Each stage is governed by specific genes for each species of Enterococcus, some being very similar to genes across multiple genera. Numerous morphological factors contribute to their pathogenesis via the production of biofilms. Biofilm-related virulence factors can be divided into secreted factors (cytolysin, secreted antigen A and gelatinase) and cell surface factors, which include pili and microbial surface components that recognize adhesive matrix molecules and aggregation substances. Biofilm formation is regulated by a mechanism called quorum sensing. This is a cell-density-dependent mechanism of intercellular communication, mediated by the expression of specific bacterial genes.

This paper aims to compile the existing literature concerning the various factors involved in the formation of biofilms by enterococci and to provide a comprehensive insight into this fascinating niche, while also proposing a number of directions for future research into biofilm eradication techniques that may target these factors. Although there are several articles that review the different steps involved in the formation of biofilms by the Enterococcus genus, the present paper offers a more comprehensive overview of the complexity of factors that govern the process of biofilm formation for this bacterium. It also aims to provide some directions for the future research of anti-biofilm molecules.

We organized the review into four parts: (a) biofilm-related secreted virulence factors; (b) biofilm-related surface proteins; (c) quorum-sensing molecules; and (d) regulators of extracellular DNA release. An overview of the factors discussed is presented in Table one.