Review

Authors: Mónica García-Solache, Louis B Rice

The genus comprises a ubiquitous group of Gram-positive bacteria that are of great relevance to human health for their role as major causative agents of health care-associated infections. The enterococci are resilient and versatile species able to survive under harsh conditions, making them well adapted to the health care environment. Two species cause the majority of enterococcal infections: and Both species demonstrate intrinsic resistance to common antibiotics, such as virtually all cephalosporins, aminoglycosides, clindamycin, and trimethoprim-sulfamethoxazole. Additionally, a remarkably plastic genome allows these two species to readily acquire resistance to further antibiotics, such as high-level aminoglycoside resistance, high-level ampicillin resistance, and vancomycin resistance, either through mutation or by horizontal transfer of genetic elements conferring resistance determinants.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterococcus; Gene Transfer, Horizontal; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Mutation

PubMed: 30700430
DOI: 10.1128/CMR.00058-18

Review

Authors: Elizabeth Fiore, Daria Van Tyne, Michael S Gilmore...

Enterococci are unusually well adapted for survival and persistence in a variety of adverse environments, including on inanimate surfaces in the hospital environment and at sites of infection. This intrinsic ruggedness undoubtedly played a role in providing opportunities for enterococci to interact with other overtly drug-resistant microbes and acquire additional resistances on mobile elements. The rapid rise of antimicrobial resistance among hospital-adapted enterococci has rendered hospital-acquired infections a leading therapeutic challenge. With about a quarter of a genome of additional DNA conveyed by mobile elements, there are undoubtedly many more properties that have been acquired that help enterococci persist and spread in the hospital setting and cause diseases that have yet to be defined. Much remains to be learned about these ancient and rugged microbes, particularly in the area of pathogenic mechanisms involved with human diseases.

Topics: Animals; Enterococcus; Gram-Positive Bacterial Infections; Humans; Interspersed Repetitive Sequences; Virulence

PubMed: 31298205
DOI: 10.1128/microbiolspec.GPP3-0053-2018

Review

Authors: Carmen Torres, Carla Andrea Alonso, Laura Ruiz-Ripa...

Enterococci are natural inhabitants of the intestinal tract in humans and many animals, including food-producing and companion animals. They can easily contaminate the food and the environment, entering the food chain. Moreover, is an important opportunistic pathogen, especially the species and , causing a wide variety of infections. This microorganism not only contains intrinsic resistance mechanisms to several antimicrobial agents, but also has the capacity to acquire new mechanisms of antimicrobial resistance. In this review we analyze the diversity of enterococcal species and their distribution in the intestinal tract of animals. Moreover, resistance mechanisms for different classes of antimicrobials of clinical relevance are reviewed, as well as the epidemiology of multidrug-resistant enterococci of animal origin, with special attention given to beta-lactams, glycopeptides, and linezolid. The emergence of new antimicrobial resistance genes in enterococci of animal origin, such as and , is highlighted. The molecular epidemiology and the population structure of and isolates in farm and companion animals is presented. Moreover, the types of plasmids that carry the antimicrobial resistance genes in enterococci of animal origin are reviewed.

Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Enterococcus; Enterococcus faecalis; Enterococcus faecium; Farms; Food Microbiology; Gastrointestinal Tract; Gram-Positive Bacterial Infections; Humans; Molecular Epidemiology; Pets

PubMed: 30051804
DOI: 10.1128/microbiolspec.ARBA-0032-2018

Review

Authors: Keith E Weaver

The study of the genetics of enterococci has focused heavily on mobile genetic elements present in these organisms, the complex regulatory circuits used to control their mobility, and the antibiotic resistance genes they frequently carry. Recently, more focus has been placed on the regulation of genes involved in the virulence of the opportunistic pathogenic species and . Little information is available concerning fundamental aspects of DNA replication, partition, and division; this article begins with a brief overview of what little is known about these issues, primarily by comparison with better-studied model organisms. A variety of transcriptional and posttranscriptional mechanisms of regulation of gene expression are then discussed, including a section on the genetics and regulation of vancomycin resistance in enterococci. The article then provides extensive coverage of the pheromone-responsive conjugation plasmids, including sections on regulation of the pheromone response, the conjugative apparatus, and replication and stable inheritance. The article then focuses on conjugative transposons, now referred to as integrated, conjugative elements, or ICEs, and concludes with several smaller sections covering emerging areas of interest concerning the enterococcal mobilome, including nonpheromone plasmids of particular interest, toxin-antitoxin systems, pathogenicity islands, bacteriophages, and genome defense.

Topics: Anti-Bacterial Agents; Bacteriophages; Conjugation, Genetic; DNA Transposable Elements; Drug Resistance, Bacterial; Enterococcus; Enterococcus faecalis; Humans; Signal Transduction; Vancomycin-Resistant Enterococci; Virulence

PubMed: 30848235
DOI: 10.1128/microbiolspec.GPP3-0055-2018

Authors: Xiaozhe Xiong, Songhai Tian, Pan Yang...

Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of β-barrel pore-forming toxins with a β-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E. faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.

Topics: Animals; Bacterial Toxins; Cattle; Enterococcus; Horses; Leukocytes, Mononuclear; Mice; Microbial Sensitivity Tests; Swine; Virulence Factors

PubMed: 35259335
DOI: 10.1016/j.cell.2022.02.002

Authors: Şerife Merve Gök, Hatice Türk Dağı, Fatih Kara...

Enterococci, which are commonly found in the environment, cause serious infections despite the absence of well-defined virulence factors and toxins. Knowing the virulence properties of enterococci is important to understand the complex pathogenic structures. In this study, we aimed to investigate the virulence factors (asa1, hyl, cylA, efa, ebp, ace, esp, gelE, sprE, fsrA, fsrB, fsrC genes, gelatinase activity, hemolysin, hydrogen peroxide and biofilm production) and antibiotic resistance of Enterococcus faecium and Enterococcus faecalis strains isolated from clinical specimens. A total of 110 enterococcus isolates which were accepted as infectious agents were included in the study. The polymerase chain reaction method was used to identify the isolates and to detect virulence genes. Characteristics of hemolysis, biofilm formation, hydrogen peroxide production and gelatinase activity were investigated by phenotypic methods. The antibiotic susceptibility test was performed with VITEK 2 automated system. E.faecalis ATCC 29212 standard strain was used as a quality control in all tests. Of the 110 enterococci isolates included in the study, 61 were identified as E.faecium and 49 as E.faecalis. The efa gene was the most frequently detected virulence gene (92.7%), followed by ace (83.6%), esp (66.4%), ebp (60.0%), cylA (50.9%), hyl (46.4%), asa1 (45.5%), gelE, sprE, fsrC (33.6%), fsrA (12.7%) and fsrB (11.8%). All genes except hyl were higher in E.faecalis isolates and the difference was statistically significant (p<0.05). Twenty-five (51%) E.faecalis and 1 (1.6%) E.faecium isolates had beta-hemolysis and the difference was statistically significant (p= 0.000). Seven (11.5%) E.faecium and 4 (8.2%) E.faecalis isolates formed biofilm, but the difference was not statistically significant (p> 0.05). Two (3.3%) E.faecium and 14 (28.6%) E.faecalis isolates exhibited gelatinase activity and the difference between the two species was statistically significant (p= 0.000). Hydrogen peroxide production was not detected in any of the isolates. The highest resistance rate was determined against ciprofloxacin (70.9%). The resistance to ampicillin was 69.1%, high level streptomycin 65.1%, high level gentamicin 39.4%, vancomycin and teicoplanin 4.5%, and linezolid 1.8%. In conclusion, our data indicated that virulence factors except hyl gene and biofilm production were higher in E.faecalis isolates but E.faecium isolates were more resistant to antibiotics. In order to prevent infection of such virulent or resistant isolates in the hospital setting, infection control measures must be followed. In vivo studies are needed for the better understanding of the virulence of enterococci.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Virulence Factors

PubMed: 32050876
DOI: 10.5578/mb.68810

Review

Authors: Yasuyoshi Ike

Enterococci belong to the group of lactic acid bacteria (LAB), and inhabit the gastrointestinal tracts of a wide variety of animals from insects and to human, and the commensal organism in humans and animals. The commensal/probiotic role of enterococci has evolved through thousands of years in mutual coexistence. Enterococcus have many favorable traits that have been appreciated in food fermentation and preservation, and many serve as probiotics to promote health. While lactobacillus have been shown to confer numerous benefits on and often regarded as health bringing organisms, enterococci have become more recognized as emerging human pathogens in recent years. Mac Callum and Hastings characterized an organism, now known to be Enterococcal faecalis, which was isolated from a lethal case of endocarditis on 1899. The report was the first detailed description of its pathogenic capabilities. Over the past few decades, multi-drug resistance enterococci have become as important health-care associated pathogen, and leading causes of drug resistance infection. The modern life style including the broad use of antibiotics in medical practice and animal husbandry have selected for the convergence of potential virulence factors to the specific enterococcus species such as E. faecium and E. faecalis. The development of modern medical care of intensive and invasive medical therapies and treatments for human disease, and existence of severe compromised patients in hospitals has contributed to the increased prevalence of these opportunistic organisms. The virulence factors converged in E. faecalis and E. faecium which have been isolated in nosocomial infections, include antibiotic resistance, extracellular proteins (toxins), extrachromosome and mobile genetic elements, cell wall components, biofilm formation, adherence factors, and colonization factor such as bacteriocin, etc. In these potential virulence factors, I presented characteristics of enterococcal conjugative plasmid, cytolysin, collagen binding protein of adhesion, bacteriocins, and drug resistances. I made reference to our original reports, and review books for this review. The review books are "Enterococci: from Commensals to Leading Causes of Drug Resistant Infection, NCBI Bookshelf. A service of the National Library of Medicine, National Institute of Health. Ed. by Michael S Gilmore, Don B Clewell, Yasuyoshi Ike, and Nathan Shankar", and "The Enterococci: Pathogenesis, Molecular Biology, and Antibiotic Resistance, Gilmore M., Clewell D., Courvadin P., Dunny G., Murray B., Rice L., (ed) 2002. ASM Press".

Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Bacteriocins; Biofilms; Cross Infection; Drug Resistance, Bacterial; Endocarditis; Enterococcus; Humans; Virulence Factors

PubMed: 28659548
DOI: 10.3412/jsb.72.189

Comparative Study Review

Authors: B E Murray

Topics: Bacterial Proteins; Enterococcus; Humans; Infant; beta-Lactamases

PubMed: 1489177
DOI: 10.1128/AAC.36.11.2355

Review

Authors: B D Jett, M M Huycke, M S Gilmore...

Enterococci are commensal organisms well suited to survival in intestinal and vaginal tracts and the oral cavity. However, as for most bacteria described as causing human disease, enterococci also possess properties that can be ascribed roles in pathogenesis. The natural ability of enterococci to readily acquire, accumulate, and share extrachromosomal elements encoding virulence traits or antibiotic resistance genes lends advantages to their survival under unusual environmental stresses and in part explains their increasing importance as nosocomial pathogens. This review discusses the current understanding of enterococcal virulence relating to (i) adherence to host tissues, (ii) invasion and abscess formation, (iii) factors potentially relevant to modulation of host inflammatory responses, and (iv) potentially toxic secreted products. Aggregation substance, surface carbohydrates, or fibronectin-binding moieties may facilitate adherence to host tissues. Enterococcus faecalis appears to have the capacity to translocate across intact intestinal mucosa in models of antibiotic-induced superinfection. Extracellular toxins such as cytolysin can induce tissue damage as shown in an endophthalmitis model, increase mortality in combination with aggregation substance in an endocarditis model, and cause systemic toxicity in a murine peritonitis model. Finally, lipoteichoic acid, superoxide production, or pheromones and corresponding peptide inhibitors each may modulate local inflammatory reactions.

Topics: Animals; Bacterial Adhesion; Cytotoxins; Enterococcus; Female; Gene Transfer Techniques; Gram-Positive Bacterial Infections; History, 19th Century; History, 20th Century; Humans; Mice; Virulence

PubMed: 7834601
DOI: 10.1128/CMR.7.4.462

Review

Authors: Yasuyoshi Ike

Topics: Animals; Anti-Bacterial Agents; Bacteriocins; DNA Transposable Elements; Drug Resistance, Bacterial; Enterococcus; Evolution, Molecular; Humans; Perforin; Transposon Resolvases; Virulence

PubMed: 26911466
DOI: 10.3412/jsb.71.1