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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 -
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 -
Signal Transduction and Targeted Therapy Feb 2021The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates...
The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH) as a coenzyme. Here, we show that oral berberine (BBR) might supply H through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH from dihydrobiopterin; the increased BH enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut-brain dialog activated by BBR's effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson's disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.
Topics: Animals; Berberine; Corpus Striatum; Dihydroxyphenylalanine; Dopamine; Enterococcus faecalis; Enterococcus faecium; Gastrointestinal Microbiome; Humans; Levodopa; Mice; Parkinson Disease; Tyrosine 3-Monooxygenase
PubMed: 33623004
DOI: 10.1038/s41392-020-00456-5 -
The Lancet. Microbe Feb 2023Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption... (Review)
Review
Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption associated with disease. This Review looks at vaccine candidates that are in development against pathogens on the 2017 WHO bacterial priority pathogen list, in addition to Clostridioides difficile and Mycobacterium tuberculosis. There were 94 active preclinical vaccine candidates and 61 active development vaccine candidates. We classified the included pathogens into the following four groups: Group A consists of pathogens for which vaccines already exist-ie, Salmonella enterica serotype Typhi, Streptococcus pneumoniae, Haemophilus influenzae type b, and M tuberculosis. Group B consists of pathogens with vaccines in advanced clinical development-ie, extra-intestinal pathogenic Escherichia coli, Salmonella enterica serotype Paratyphi A, Neisseria gonorrhoeae, and C difficile. Group C consists of pathogens with vaccines in early phases of clinical development-ie, enterotoxigenic E coli, Klebsiella pneumoniae, non-typhoidal Salmonella, Shigella spp, and Campylobacter spp. Finally, group D includes pathogens with either no candidates in clinical development or low development feasibility-ie, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Helicobacter pylori, Enterococcus faecium, and Enterobacter spp. Vaccines are already important tools in reducing antimicrobial resistance and future development will provide further opportunities to optimise the use of vaccines against resistance.
Topics: Anti-Bacterial Agents; Bacterial Vaccines; Escherichia coli; Drug Resistance, Bacterial; Enterococcus faecium
PubMed: 36528040
DOI: 10.1016/S2666-5247(22)00303-2 -
Frontiers in Cellular and Infection... 2023The human-bacterial association is long-known and well-established in terms of both augmentations of human health and attenuation. However, the growing incidents of... (Review)
Review
The human-bacterial association is long-known and well-established in terms of both augmentations of human health and attenuation. However, the growing incidents of nosocomial infections caused by the ESKAPE pathogens (, , , , , and sp.) call for a much deeper understanding of these organisms. Adopting a holistic approach that includes the science of infection and the recent advancements in preventing and treating infections is imperative in designing novel intervention strategies against ESKAPE pathogens. In this regard, this review captures the ingenious strategies commissioned by these master players, which are teamed up against the defenses of the human team, that are equally, if not more, versatile and potent through an analogy. We have taken a basketball match as our analogy, dividing the human and bacterial species into two teams playing with the ball of health. Through this analogy, we make the concept of infectious biology more accessible.
Topics: Humans; Quorum Sensing; Anti-Bacterial Agents; Virulence; Staphylococcal Infections; Enterococcus faecium
PubMed: 37457962
DOI: 10.3389/fcimb.2023.1159798 -
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 -
ELife Apr 2024An enzyme that remodels the cell wall of helps these gut bacteria to divide and generate peptide fragments that enhance the immune response against cancer.
An enzyme that remodels the cell wall of helps these gut bacteria to divide and generate peptide fragments that enhance the immune response against cancer.
PubMed: 38578679
DOI: 10.7554/eLife.97277 -
Scientific Reports Jun 2022Gut dysbiosis is closely associated with the outbreak of inflammatory bowel disease (IBD) and psychiatric disorder. The Enterobacteriaceae population was higher in the...
Gut dysbiosis is closely associated with the outbreak of inflammatory bowel disease (IBD) and psychiatric disorder. The Enterobacteriaceae population was higher in the feces of patients with inflammatory bowel disease (IBD-F) than in those of healthy control volunteers (HC-F). The Enterococcaceae and Lactobacillaceae populations were higher in the feces of IBD patients with depression (IBD/D-F) vs. the feces of IBD patients without depression (IBD/D-F). Therefore, we examined the effects of Klebsiella oxytoca, Escherichia coli, Cronobacter sakazakii, Enterococcus faecium, and Pediococcus acidolactici overpopulated in IBD/D-F and their byproducts LPS and exopolysaccharide (EPS) on the occurrence of depression and colitis in mice. Oral gavages of Klebsiella oxytoca, Escherichia coli, and Cronobacter sakazakii belonging to Enterobacteriaceae, singly or together, caused dose-dependently colitis and depression-like behaviors in germ-free and specific-pathogen-free mice. Although Enterococcus faecium and Pediococcus acidolactici did not significantly cause colitis and depression-like behaviors, they significantly deteriorated Klebsiella oxytoca- or Escherichia coli-induced colitis, neuroinflammation, and anxiety/depression-like behaviors and increased blood LPS, corticosterone, and IL-6 levels. The EPSs from Enterococcus faecium and Pediococcus acidolactici also worsened Klebsiella oxytoca LPS-induced colitis, neuroinflammation, and depression-like behaviors in mice and increased the translocation of fluorescein isothiocyanate-conjugated LPS into the hippocampus. However, Bifidobacterium longum, which was lower in IBD/D-F vs. IBD/D-F, or its EPS suppressed them. In conclusion, Enterococcus faecium and Pediococcus acidolactici, known as a probiotic strain, and their EPSs may be a risk factor for the outbreak of depression and IBD.
Topics: Animals; Colitis; Depression; Enterobacteriaceae; Enterococcus faecium; Escherichia coli; Humans; Inflammatory Bowel Diseases; Lipopolysaccharides; Mice; Pediococcus acidilactici
PubMed: 35672451
DOI: 10.1038/s41598-022-13629-9 -
Nature Communications Apr 2022The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, we show that vancomycin resistance in...
The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, we show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics (such as lefamulin), which target the bacterial ribosome. The trade-off between vancomycin and pleuromutilins is mediated by epistasis between the van gene cluster and msrC, encoding an ABC-F protein that protects bacterial ribosomes from antibiotic targeting. In mouse models of vancomycin-resistant E. faecium colonization and septicemia, pleuromutilin treatment reduces colonization and improves survival more effectively than standard therapy (linezolid). Our findings suggest that pleuromutilins may be useful for the treatment of vancomycin-resistant E. faecium infections.
Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Collateral Sensitivity; Enterococcus faecium; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Polycyclic Compounds; Vancomycin; Pleuromutilins
PubMed: 35393429
DOI: 10.1038/s41467-022-29493-0 -
Antimicrobial Resistance and Infection... Aug 2020Early in its evolution, Enterococcus faecium acquired traits that allowed it to become a successful nosocomial pathogen. E. faecium inherent tenacity to build resistance... (Review)
Review
Early in its evolution, Enterococcus faecium acquired traits that allowed it to become a successful nosocomial pathogen. E. faecium inherent tenacity to build resistance to antibiotics and environmental stressors that allows the species to thrive in hospital environments. The continual wide use of antibiotics in medicine has been an important driver in the evolution of E. faecium becoming a highly proficient hospital pathogen.For successful prevention and reduction of nosocomial infections with vancomycin resistant E. faecium (VREfm), it is essential to focus on reducing VREfm carriage and spread. The aim of this review is to incorporate microbiological insights of E. faecium into practical infection control recommendations, to reduce the spread of hospital-acquired VREfm (carriage and infections). The spread of VREfm can be controlled by intensified cleaning procedures, antibiotic stewardship, rapid screening of VREfm carriage focused on high-risk populations, and identification of transmission routes through accurate detection and typing methods in outbreak situations. Further, for successful management of E. faecium, continual innovation in the fields of diagnostics, treatment, and eradication is necessary.
Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Cross Infection; Disease Outbreaks; Enterococcus faecium; Genome, Bacterial; Genotype; Gram-Positive Bacterial Infections; Humans; Infection Control; Microbial Sensitivity Tests; Multilocus Sequence Typing
PubMed: 32778149
DOI: 10.1186/s13756-020-00770-1