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A lactic acid bacterial strain was isolated from human fecal specimen and identified as Enterococcus faecalis SL-5. The isolated strain showed antimicrobial activity against Gram-positive pathogens assayed, especially the highest activity against Propionibacterium acnes . The antimicrobial substance was purified and verified as a bacteriocin (named ESL5) of E. faecalis SL-5 by activity-staining using P. acnes as an indicator. N-terminal sequence of ESL5 was determined (MGAIAKLVAK) and sequence analysis revealed that it is almost identical to the some of enterocins including L50A/B of E. faecium L50 and MR10A/B of E. faecalis MRR 10-3. From the sequencing data of L50A/B structural genes, the nucleotide sequence showed 100% identity with that of the MR10A/B structural genes, implying that ESL5 is an equivalent of enterocin MR10. Meanwhile, we also tested the therapeutic effect of anti- P. acnes activity in patients with mild to moderate acne because of its pathogenic role to acne vulgaris. For this purpose, a concentrated powder of CBT SL-5 was prepared using cell-free culture supernatant (CFCS) of E. faecalis SL-5 and included in a lotion for application in the patients. The study showed that CBT SL-5 lotion significantly reduced the inflammatory lesions like pustules compared to the placebo lotion. Therefore our results indicate that the anti- P. acnes activity produced by E. faecalis SL-5 has potential role to the treatment of acne as an alternative to topical antibiotics.

For a One-Health investigation of antimicrobial resistance (AMR) in Enterococcus spp., isolates from humans and beef cattle along with abattoirs, manured fields, natural streams, and wastewater from both urban and cattle feedlot sources were collected over two years. Species identification of Enterococcus revealed distinct associations across the continuum. Of the 8430 isolates collected, Enterococcus faecium and Enterococcus faecalis were the main species in urban wastewater (90%) and clinical human isolates (99%); Enterococcus hirae predominated in cattle (92%) and feedlot catch-basins (60%), whereas natural streams harbored environmental Enterococcus spp. Whole-genome sequencing of E. faecalis (n = 366 isolates) and E. faecium (n = 342 isolates), revealed source clustering of isolates, indicative of distinct adaptation to their respective environments. Phenotypic resistance to tetracyclines and macrolides encoded by tet(M) and erm(B) respectively, was prevalent among Enterococcus spp. regardless of source. For E. faecium from cattle, resistance to β-lactams and quinolones was observed among 3% and 8% of isolates respectively, compared to 76% and 70% of human clinical isolates. Clinical vancomycin-resistant E. faecium exhibited high rates of multi-drug resistance, with resistance to all β-lactam, macrolides, and quinolones tested. Differences in the AMR profiles among isolates reflected antimicrobial use practices in each sector of the One-Health continuum.

Commensal and generally harmless in healthy individuals, Enterococcus faecalis causes opportunistic infections in immunocompromised patients. Plasmid-cured E. faecalis strain VE14089, derived from sequenced reference strain V583, is widely used for functional studies due to its improved genetic amenability. Although strain VE14089 has no major DNA rearrangements, with the exception of an ϳ20-kb integrated region of pTEF1 plasmid, the strain presented significant growth differences from the V583 reference strain of our collection (renamed VE14002). In the present study, genome sequencing of strain VE14089 identified additional point mutations. Excision of the integrated pTEF1 plasmid region and sequential restoration of wild-type alleles showing nonsilent mutations were performed to obtain the VE18379 reference-derivative strain. Recovery of the growth ability of the restored VE18379 strain at a level similar to that seen with the reference strain points to GreA and Spx as bacterial fitness determinants. Virulence potential in Galleria mello-nella and intestinal colonization in mouse demonstrated host adaptation of the VE18379 strain equivalent to VE14002 host adaptation. We further demonstrated that deletion of the 16.8-kb variable region of the epa locus recapitulates the key role of Epa decoration in host adaptation, providing a genetic system to study the role of specific epa-variable regions in host adaptation independently of other genetic variations. IMPORTANCE E. faecalis strain VE14089 was derived from V583 cured of its plas-mids. Although VE14089 had no major DNA rearrangements, it presented significant growth and host adaptation differences from the reference strain V583 of our collection. To construct a strain with better fitness, we sequenced the genome of VE14089, identified single nucleotide polymorphisms (SNPs), and repaired the genes that could account for these changes. Using this reference-derivative strain, we provide a novel genetic system to understand the role of the variable region of epa in the enterococcal lifestyle.

The efficacy of l -dopa treatment for Parkinson's disease is hugely variable between individuals, depending on the composition of their microbiota. l -Dopa is decarboxylated into active dopamine, but if the gut microbiota metabolize l -dopa before it crosses the blood-brain barrier, medication is ineffective. Maini Rekdal et al. found that different species of bacterium are involved in l -dopa metabolism (see the Perspective by O'Neill). Tyrosine decarboxylase (TDC) from Enterococcus faecalis and dopamine dehydroxylase (Dadh) from Eggerthella lenta A2 sequentially metabolized l -dopa into m -tyramine. The microbial l -dopa decarboxylase can be inactivated by ( S )-α-fluoromethyltyrosine (AFMT), which indicates possibilities for developing combinations of Parkinson's drugs to circumvent microbial inactivation. Science , this issue p. eaau6323 ; see also p. 1030 An interspecies metabolic pathway allows human gut bacteria to metabolize the Parkinson’s drug levodopa. The human gut microbiota metabolizes the Parkinson’s disease medication Levodopa ( l -dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l -dopa metabolism. Conversion of l -dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed by transformation of dopamine to m -tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta . These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l -dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson’s patient microbiotas and increases l -dopa bioavailability in mice.

Background Enterococcus is ubiquitous in nature and is a commensal of both the bovine and human gastrointestinal (GI) tract. It is also associated with clinical infections in humans. Subtherapeutic administration of antibiotics to cattle selects for antibiotic resistant enterococci in the bovine GI tract. Antibiotic resistance genes (ARGs) may be present in enterococci following antibiotic use in cattle. If located on mobile genetic elements (MGEs) their dissemination between Enterococcus species and to pathogenic bacteria may be promoted, reducing the efficacy of antibiotics. Results We present a comparative genomic analysis of twenty-one Enterococcus spp. isolated from bovine feces including Enterococcus hirae ( n  = 10), Enterococcus faecium ( n  = 3), Enterococcus villorum ( n  = 2), Enterococcus casseliflavus ( n  = 2), Enterococcus faecalis ( n  = 1), Enterococcus durans ( n  = 1), Enterococcus gallinarum ( n  = 1) and Enterococcus thailandicus ( n  = 1). The analysis revealed E. faecium and E. faecalis from bovine feces share features with human clinical isolates, including virulence factors. The Tn 917 transposon conferring macrolide-lincosamide-streptogramin B resistance was identified in both E. faecium and E. hirae , suggesting dissemination of ARGs on MGEs may occur in the bovine GI tract. An E. faecium isolate was also identified with two integrative conjugative elements (ICEs) belonging to the Tn 916 family of ICE, Tn 916 and Tn 5801 , both conferring tetracycline resistance. Conclusions This study confirms the presence of enterococci in the bovine GI tract possessing ARGs on MGEs, but the predominant species in cattle, E. hirae is not commonly associated with infections in humans. Analysis using additional complete genomes of E. faecium from the NCBI database demonstrated differential clustering of commensal and clinical isolates, suggesting that these strains may be specifically adapted to their respective environments.

The authors develop a mouse model of Enterococcus faecalis colonization to show that enterococci harbouring the bacteriocin-expressing plasmid pPD1 replace indigenous enterococci and have the ability to transfer the plasmid to other enterococci, which enhances the stability of the bacteriocin-expressing bacteria in the gut; this result suggests a therapeutic approach that leverages niche-specificity to eliminate antibiotic-resistant bacteria from infected individuals. Competition defeats multidrug-resistant bacteria Enterococcus faecalis is a normal gut bacterium and is usually harmless, but it can cause a variety of hospital-acquired infections in which its acquisition of antibiotic resistance makes it hard to treat. Nita Salzman and colleagues develop a mouse model of E. faecalis infection and use it to show that enterococci harbouring the bacteriocin-expressing plasmid pPD1 replace indigenous enterococci and have the ability to transfer the plasmid to other enterococci, thereby enhancing the stability of the bacteriocin-expressing bacteria in the gut. However, colonization by a strain in which the plasmid was not passed on resulted in clearance of other enterococci strains from the gut — including those resistant to the antibiotic vancomycin. This result suggests a way of using bacteriocin-producing bacteria as targeted therapeutics designed to clear competing multidrug-resistant strains from infected individuals. Enterococcus faecalis is both a common commensal of the human gastrointestinal tract and a leading cause of hospital-acquired infections 1 . Systemic infections with multidrug-resistant enterococci occur subsequent to gastrointestinal colonization 2 . Preventing colonization by multidrug-resistant E. faecalis could therefore be a valuable approach towards limiting infection. However, little is known about the mechanisms E. faecalis uses to colonize and compete for stable gastrointestinal niches. Pheromone-responsive conjugative plasmids encoding bacteriocins are common among enterococcal strains 3 and could modulate niche competition among enterococci or between enterococci and the intestinal microbiota. We developed a model of colonization of the mouse gut with E. faecalis , without disrupting the microbiota, to evaluate the role of the conjugative plasmid pPD1 expressing bacteriocin 21 (ref. 4 ) in enterococcal colonization. Here we show that E. faecalis harbouring pPD1 replaces indigenous enterococci and outcompetes E. faecalis lacking pPD1. Furthermore, in the intestine, pPD1 is transferred to other E. faecalis strains by conjugation, enhancing their survival. Colonization with an E. faecalis strain carrying a conjugation-defective pPD1 mutant subsequently resulted in clearance of vancomycin-resistant enterococci, without plasmid transfer. Therefore, bacteriocin expression by commensal bacteria can influence niche competition in the gastrointestinal tract, and bacteriocins, delivered by commensals that occupy a precise intestinal bacterial niche, may be an effective therapeutic approach to specifically eliminate intestinal colonization by multidrug-resistant bacteria, without profound disruption of the indigenous microbiota.

Enterococcus faecalis is a commensal and nosocomial pathogen, which is also ubiquitous in animals and insects, representing a classical generalist microorganism. Here, we study E. faecalis isolates ranging from the pre-antibiotic era in 1936 up to 2018, covering a large set of host species including wild birds, mammals, healthy humans, and hospitalised patients. We sequence the bacterial genomes using short- and long-read techniques, and identify multiple extant hospital-associated lineages, with last common ancestors dating back as far as the 19th century. We find a population cohesively connected through homologous recombination, a metabolic flexibility despite a small genome size, and a stable large core genome. Our findings indicate that the apparent hospital adaptations found in hospital-associated E. faecalis lineages likely predate the “modern hospital” era, suggesting selection in another niche, and underlining the generalist nature of this nosocomial pathogen. Enterococcus faecalis is a commensal microorganism of animals, insects and humans, but also a nosocomial pathogen. Here, the authors analyse genomic sequences from E. faecalis isolates from animals and humans, and find that the last common ancestors of multiple hospital-associated lineages date to the pre-antibiotic era.

Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. They hold great potential in the fight against antibiotic resistant bacteria, including ESKAPE pathogens. Engineered live biotherapeutic products (eLBPs) that secrete bacteriocins can be created to deliver targeted bacteriocin production. Here we develop a modular bacteriocin secretion platform that can be used to express and secrete multiple bacteriocins from non-pathogenic Escherichia coli host strains. As a proof of concept we create Enterocin A (EntA) and Enterocin B (EntB) secreting strains that show strong antimicrobial activity against Enterococcus faecalis and Enterococcus faecium in vitro, and characterise this activity in both solid culture and liquid co-culture. We then develop a Lotka-Volterra model that can be used to capture the interactions of these competitor strains. We show that simultaneous exposure to EntA and EntB can delay Enterococcus growth. Our system has the potential to be used as an eLBP to secrete additional bacteriocins for the targeted killing of pathogenic bacteria. Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. In this work, authors develop a bacteriocin secretion platform, and test, in a proof-of-concept study, antimicrobial efficacy against Enterococcus faecalis and Enterococcus faecium .

Background Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level. Results We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn’s disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10 −/− mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients. Conclusions E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.

Subclinical mastitis poses a hidden threat to dairy productivity and animal health, often harbouring antimicrobial-resistant pathogens. It is becoming increasingly recognized that Enterococcus species cause mastitis in dairy cows. Accurately characterizing the regional epidemiology of enterococcal mastitis, determining its correlations with management variables, and comprehending its effects on udder health all depend on accurate species information. This study investigated the occurrence, antibiotic resistance and virulence factors of Enterococcus faecalis and Enterococcus faecium in cow dung and milk samples from cows with subclinical mastitis. Subclinical mastitis was identified in 39.0% (68/174) of cows and 27.8% (194/696) of quarters, based on results from the California Mastitis Test (CMT) and somatic cell counts (SCC), respectively. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS) and Polymerase Chain Reaction (PCR) targeting the ddl gene confirmed the predominance of E. faecalis (93%) and E. faecium (6.4%) in milk samples, while cow dung samples yielded only E. faecalis (100%). Notably, among the E. faecalis isolates from milk samples, 17.2% exhibited vancomycin resistance, whereas streptomycin resistance was found in a smaller proportion of isolates (6.8%). All (100%) E. faecium isolates from the same milk samples showed resistance to vancomycin. The findings also revealed that 11 (32.3%) of E. faecium isolates from cow dung were resistant to vancomycin. Multidrug resistance (MDR) was observed in 20.6% of milk and 6.8% of cow dung isolates. The vanA gene was the most prevalent antibiotic resistance gene (ARG), detected in 96% of E. faecalis isolates. Virulence profiling of Enterococcus spp. isolates showed varying gene prevalence in milk ( asa1 : 33.3%, ace : 12.7%, esp : 10%) and cow dung samples ( gelE : 53.2%, hyl : 38.2%). This study has indicated a significant occurrence of antimicrobial-resistant E. faecalis and E. faecium strains obtained from subclinical cattle mastitis. These findings emphasize the role of Enterococcus spp., especially vancomycin-resistant strains, as emerging threats in bovine subclinical mastitis, with possible implications for zoonotic transmission and antimicrobial stewardship in dairy systems.