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Microbiology Spectrum Jul 2019Enterococci are unusually well adapted for survival and persistence in a variety of adverse environments, including on inanimate surfaces in the hospital environment and... (Review)
Review
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 -
Infectious Disease Clinics of North... Dec 2020Serious infections owing to vancomycin-resistant enterococci have historically proven to be difficult clinical cases, requiring combination therapy and management of... (Review)
Review
Serious infections owing to vancomycin-resistant enterococci have historically proven to be difficult clinical cases, requiring combination therapy and management of treatment-related toxicity. Despite the introduction of new antibiotics with activity against vancomycin-resistant enterococci to the therapeutic armamentarium, significant challenges remain. An understanding of the factors driving the emergence of resistance in vancomycin-resistant enterococci, the dynamics of gastrointestinal colonization and microbiota-mediated colonization resistance, and the mechanisms of resistance to the currently available therapeutics will permit clinicians to be better prepared to tackle these challenging hospital-associated pathogens.
Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterococcus faecium; Gastrointestinal Microbiome; Gram-Positive Bacterial Infections; Humans; Vancomycin-Resistant Enterococci
PubMed: 33131572
DOI: 10.1016/j.idc.2020.08.004 -
Microbial Genomics Jul 2019Vancomycin-resistant Enterococcus faecium (VREfm) is a globally significant public health threat and was listed on the World Health Organization's 2017 list of... (Review)
Review
Vancomycin-resistant Enterococcus faecium (VREfm) is a globally significant public health threat and was listed on the World Health Organization's 2017 list of high-priority pathogens for which new treatments are urgently needed. Treatment options for invasive VREfm infections are very limited, and outcomes are often poor. Whole-genome sequencing is providing important new insights into VREfm evolution, drug resistance and hospital adaptation, and is increasingly being used to track VREfm transmission within hospitals to detect outbreaks and inform infection control practices. This mini-review provides an overview of recent data on the use of genomics to understand and respond to the global problem of VREfm.
Topics: Disease Outbreaks; Enterococcus faecium; Genome, Bacterial; Genomics; Gram-Positive Bacterial Infections; Humans; Phylogeny; Vancomycin Resistance; Vancomycin-Resistant Enterococci; Whole Genome Sequencing
PubMed: 31329096
DOI: 10.1099/mgen.0.000283 -
Science (New York, N.Y.) Oct 2020Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice...
Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These "elite-survivors" harbored distinct gut microbiota that developed after radiation and protected against radiation-induced damage and death in both germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa and were associated with postradiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy, who also displayed milder gastrointestinal dysfunction. In our study in mice, metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The administration of these metabolites caused long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses.
Topics: Acute Radiation Syndrome; Animals; Clostridiales; Enterococcaceae; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Metabolomics; Mice; Mice, Inbred C57BL; Radiation Protection; Survivors; Tryptophan
PubMed: 33122357
DOI: 10.1126/science.aay9097 -
Nature Nov 2022Enteric pathogens are exposed to a dynamic polymicrobial environment in the gastrointestinal tract. This microbial community has been shown to be important during...
Enteric pathogens are exposed to a dynamic polymicrobial environment in the gastrointestinal tract. This microbial community has been shown to be important during infection, but there are few examples illustrating how microbial interactions can influence the virulence of invading pathogens. Here we show that expansion of a group of antibiotic-resistant, opportunistic pathogens in the gut-the enterococci-enhances the fitness and pathogenesis of Clostridioides difficile. Through a parallel process of nutrient restriction and cross-feeding, enterococci shape the metabolic environment in the gut and reprogramme C. difficile metabolism. Enterococci provide fermentable amino acids, including leucine and ornithine, which increase C. difficile fitness in the antibiotic-perturbed gut. Parallel depletion of arginine by enterococci through arginine catabolism provides a metabolic cue for C. difficile that facilitates increased virulence. We find evidence of microbial interaction between these two pathogenic organisms in multiple mouse models of infection and patients infected with C. difficile. These findings provide mechanistic insights into the role of pathogenic microbiota in the susceptibility to and the severity of C. difficile infection.
Topics: Animals; Humans; Mice; Anti-Bacterial Agents; Arginine; Clostridioides difficile; Disease Models, Animal; Drug Resistance, Bacterial; Enterococcus; Gastrointestinal Microbiome; Intestines; Leucine; Microbial Interactions; Ornithine; Virulence; Disease Susceptibility
PubMed: 36385534
DOI: 10.1038/s41586-022-05438-x -
Cell Mar 2022Enterococci 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)...
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 -
Science (New York, N.Y.) Nov 2019Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are...
Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.
Topics: Aged; Animals; Dysbiosis; Enterococcus; Feces; Female; Gastrointestinal Microbiome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Intestines; Lactose; Male; Mice; Microbiota; Middle Aged; RNA, Ribosomal, 16S; Sequence Analysis, RNA; Transplantation, Homologous
PubMed: 31780560
DOI: 10.1126/science.aax3760 -
Cell Host & Microbe Oct 2022Interactions between the enteric nervous system (ENS) and intestinal epithelium are thought to play a vital role in intestinal homeostasis. How the ENS monitors the...
Interactions between the enteric nervous system (ENS) and intestinal epithelium are thought to play a vital role in intestinal homeostasis. How the ENS monitors the frontier with commensal and pathogenic microbes while maintaining epithelial function remains unclear. Here, by combining subdiaphragmatic vagotomy with transcriptomics, chemogenetic strategy, and coculture of enteric neuron-intestinal organoid, we show that enteric neurons expressing VIP shape the α1,2-fucosylation of intestinal epithelial cells (IECs). Mechanistically, neuropeptide VIP activates fut2 expression via the Erk1/2-c-Fos pathway through the VIPR1 receptor on IECs. We further demonstrate that perturbation of enteric neurons leads to gut dysbiosis through α1,2-fucosylation in the steady state and results in increased susceptibility to alcohol-associated liver disease (ALD). This was attributed to an imbalance between beneficial Bifidobacterium and opportunistic pathogenic Enterococcus faecalis in ALD. In addition, Bifidobacterium α1,2-fucosidase may promote Bifidobacterium adhesion to the mucosal surface, which restricts Enterococcus faecalis overgrowth and prevents ALD progression.
Topics: Bifidobacterium; Enteric Nervous System; Enterococcus faecalis; Epithelium; Gastrointestinal Microbiome; Homeostasis; Neurons; alpha-L-Fucosidase
PubMed: 36150396
DOI: 10.1016/j.chom.2022.09.001 -
Scientific Reports Dec 2020The aim of this study was to investigate how carbohydrates (glucose or sucrose) affect the characteristics of Enterococcus faecalis (E. faecalis) planktonic and biofilm...
The aim of this study was to investigate how carbohydrates (glucose or sucrose) affect the characteristics of Enterococcus faecalis (E. faecalis) planktonic and biofilm in vitro. For this study, E. faecalis was cultured in tryptone-yeast extract broth with 0% glucose + 0% sucrose, 0.5% glucose, 1% glucose, 0.5% sucrose, or 1% sucrose. Viability of E. faecalis was examined by colony forming unit counting assays. Biofilm formation was assessed by measuring extracellular DNA (eDNA), a component of the biofilm matrix. Quantitative real-time PCR (qRT-PCR) was performed to investigate the expression of virulence-associated genes. Field emission scanning electron microscopy analysis, confocal laser scanning microscopy analysis, and crystal violet colorimetric assay were conducted to study E. faecalis biofilms. E. faecalis showed the highest viability and eDNA levels in 1% sucrose medium in biofilms. The result of qRT-PCR showed that the virulence-associated genes expressed highest in 1% sucrose-grown biofilms and in 1% glucose-grown planktonic cultures. E. faecalis showed highly aggregated biofilms and higher bacteria and exopolysaccharide (EPS) bio-volume in sucrose than in 0% glucose + 0% sucrose or glucose. The results indicate that the production of eDNA and EPS and expression of virulence-associated genes in E. faecalis are affected by the concentration of carbohydrates in biofilm or planktonic culture.
Topics: Culture Media; Enterococcus faecalis; Extracellular Polymeric Substance Matrix; Microbial Viability; Virulence
PubMed: 33318537
DOI: 10.1038/s41598-020-78998-5 -
Mikrobiyoloji Bulteni Jan 2020Enterococci, which are commonly found in the environment, cause serious infections despite the absence of well-defined virulence factors and toxins. Knowing the...
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