Global status of antimicrobial resistance in clinical Enterococcus faecalis isolates: systematic review and meta-analysis
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SUBMITTER: Guan L
PROVIDER: S-EPMC11344933 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Opportunistic infections caused by multidrug-resistant Enterococcus faecalis strains are a significant clinical challenge. Eravacycline (Erava) is a synthetic fluorocycline structurally similar to tigecycline (Tige) that exhibits robust antimicrobial activity against Gram-positive bacteria. This study investigated the in vitro antimicrobial activity and heteroresistance risk of Eravacycline (Erava) in clinical E. faecalis isolates from China along with the mechanism of Erava resistance. A total of 276 non-duplicate E. faecalis isolates were retrospectively collected from a tertiary care hospital in China. Heteroresistance to Erava and the influence of tetracycline (Tet) resistance genes on Erava susceptibility were examined. To clarify the molecular basis for Erava resistance, E. faecalis variants exhibiting Erava-induced resistance were selected under Erava pressure. The relative transcript levels of six candidate genes linked to Erava susceptibility were determined by quantitative reverse-transcription PCR, and their role in Erava resistance and heteroresistance was evaluated by in vitro overexpression experiments. We found that Erava minimum inhibitory concentrations (MICs) against clinical E. faecalis isolates ranged from ≤0.015 to 0.25 mg/l even in strains harboring Tet resistance genes. The detection frequency of Erava heteroresistance in isolates with MICs ≤ 0.06, 0.125, and 0.25 mg/l were 0.43% (1/231), 7.5% (3/40), and 0 (0/5), respectively. No mutations were detected in the 30S ribosomal subunit gene in Erava heteroresistance-derived clones, although mutations in this subunit conferred cross resistance to Tige in Erava-induced resistant E. faecalis. Overexpressing RS00630 (encoding a bone morphogenetic protein family ATP-binding cassette transporter substrate-binding protein) in E. faecalis increased the frequency of Erava and Tige heteroresistance, whereas RS12140, RS06145, and RS06880 overexpression conferred heteroresistance to Tige only. These results indicate that Erava has potent in vitro antimicrobial activity against clinical E. faecalis isolates from China and that Erava heteroresistance can be induced by RS00630 overexpression.
| S-EPMC7261854 | biostudies-literature
Project description:BackgroundVibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures.ObjectiveThis meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples.MethodsWe systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0).ResultsA total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05).ConclusionsFluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.
| S-EPMC9036709 | biostudies-literature
Project description:Enterococcus faecalis and E. faecium are the major pathogens causing community- and healthcare-associated infections, with an ability to acquire resistance to multiple antimicrobials. The present study was conducted to determine the prevalence of virulence factors, drug resistance and its genetic determinants, and clonal lineages of E. faecalis and E. faecium clinical isolates in northern Japan. A total of 480 (426 E. faecalis and 54 E. faecium) isolates collected over a four-month period were analyzed. Three virulence factors promoting bacterial colonization (asa1, efaA, and ace) were more prevalent among E. faecalis (46-59%) than E. faecium, while a similar prevalence of enterococcal surface protein gene (esp) was found in these species. Between E. faecalis and E. faecium, an evident difference was noted for resistance to erythromycin, gentamicin, and levofloxacin and its responsible resistance determinants. Oxazolidinone resistance gene optrA and phenicol exporter gene fexA were identified in an isolate of E. faecalis belonging to ST480 and revealed to be located on a cluster similar to those of isolates reported in other Asian countries. The E. faecalis isolates analyzed were differentiated into 12 STs, among which ST179 and ST16 of clonal complex (CC) 16 were the major lineage. Nearly all the E. faecium isolates were assigned into CC17, which consisted of 10 different sequence types (STs), including a dominant ST17 containing multidrug resistant isolates and ST78 with isolates harboring the hyaluronidase gene (hyl). The present study revealed the genetic profiles of E. faecalis and E. faecium clinical isolates, with the first identification of optrA in ST480 E. faecalis in Japan.
| S-EPMC9855154 | biostudies-literature
Project description:Enterococcus faecalis (E. faecalis) has rapidly acquired resistance to multiple antimicrobials, and the antimicrobial resistance of E. faecalis from broiler breeders has been implicated in its vertical transmission to their offspring. The objective of this study was to investigate the antimicrobial resistance and genetic diversity of commensal E. faecalis isolated from the broiler breeder farms. Among a total of 229 E. faecalis isolates from 9 broiler breeder farms, the highest resistance rate was observed in tetracycline (78.2%), followed by doxycycline (58.1%) and erythromycin (43.7%), and the prevalence of antimicrobial resistance showed significant differences among the 9 broiler breeder farms (P < 0.05). The tetM gene (77.1%) and ermB gene (85.0%) were detected at the highest levels in 179 TE-and 100 E-resistant isolates, respectively. Twenty-four high-level gentamicin-resistant isolates carried aac(6″)Ie-aph(2″)-la gene, and 9 high-level ciprofloxacin-resistant isolates showed point mutations in both gyrA and parC genes. All high-level gentamicin-resistant or high-level ciprofloxacin-resistant isolates showed one of the two different virulence gene patterns, ace-asa1-efaA-gelE complex or ace-efaA-gelE complex. These results indicate that constant epidemiological monitoring at the breeder level is required to prevent the pyramidal transmission of antimicrobial-resistant E. faecalis.
| S-EPMC7597544 | biostudies-literature
Project description:Enterococcus, a Gram-positive facultative anaerobic cocci belonging to the lactic acid bacteria of the phylum Firmicutes, is known to be able to resist a wide range of hostile conditions such as different pH levels, high concentration of NaCl (6.5%), and the extended temperatures between 5(°)C and 65(°)C. Despite being the third most common nosocomial pathogen, our understanding on its virulence factors is still poorly understood. The current study was aimed to determine the prevalence of different virulence genes in Enterococcus faecalis and Enterococcus faecium. For this purpose, 79 clinical isolates of Malaysian enterococci were evaluated for the presence of virulence genes. pilB, fms8, efaAfm, and sgrA genes are prevalent in all clinical isolates. In conclusion, the pathogenicity of E. faecalis and E. faecium could be associated with different virulence factors and these genes are widely distributed among the enterococcal species.
| S-EPMC4124215 | biostudies-literature
Project description:Three distinct Enterococcus faecalis VanE-type isolates-BM4574, BM4575, and BM4576-obtained in Australia were studied. Expression of the resistance genes was constitutive in BM4575, probably due to a 2-bp deletion into the vanSE gene, and inducible in BM4574 and BM4576. Transcription analysis of the vanE operons suggested that the five genes were cotranscribed from an initiation site located 25 bp upstream from the ATG start codon of vanE.
| S-EPMC529234 | biostudies-literature
Project description:This study presents the empirical findings of an in-depth genomic analysis of Enterococcus faecalis and Enterococcus lactis isolates from South Africa. It offers valuable insights into their genetic characteristics and their significant implications for public health. The study uncovers nuanced variations in the gene content of these isolates, despite their similar GC contents, providing a comprehensive view of the evolutionary diversity within the species. Genomic islands are identified, particularly in E. faecalis, emphasizing its propensity for horizontal gene transfer and genetic diversity, especially in terms of antibiotic resistance genes. Pangenome analysis reveals the existence of a core genome, accounting for a modest proportion of the total genes, with 2157 core genes, 1164 shell genes, and 4638 cloud genes out of 7959 genes in 52 South African E. faecalis genomes (2 from this study, 49 south Africa genomes downloaded from NCBI, and E. faecalis reference genome). Detecting large-scale genomic rearrangements, including chromosomal inversions, underscores the dynamic nature of bacterial genomes and their role in generating genetic diversity. The study uncovers an array of antibiotic resistance genes, with trimethoprim, tetracycline, glycopeptide, and multidrug resistance genes prevalent, raising concerns about the effectiveness of antibiotic treatment. Virulence gene profiling unveils a diverse repertoire of factors contributing to pathogenicity, encompassing adhesion, biofilm formation, stress resistance, and tissue damage. These empirical findings provide indispensable insights into these bacteria's genomic dynamics, antibiotic resistance mechanisms, and virulence potential, underlining the pressing need to address antibiotic resistance and implement robust control measures.
| S-EPMC11300488 | biostudies-literature
Project description:ObjectivesTo evaluate the prevalence of some virulence genes among 510 clinical Enterococcus spp. isolates and to assess the association of those genes with the species, infection site, and patient group (inpatients/outpatients).MethodsAdhesins genes (aggregation substances agg and asa1 of Enterococcus faecalis and Enterococcus faecium, respectively), enterococcal surface protein (esp), endocarditis-specific antigen A (efaA), collagen-binding proteins (ace/acm)); invasins (hyaluronidase (hyl) and gelatinase (gelE)); cytotoxines (activation of cytolysin (cylA) in E. faecalis); and modulators of the host immunity and inflammation (enhanced expression pheromone (eep) in E. faecalis) were detected by polymerase chain reaction.ResultsThe overall prevalence was: esp - 44.3%, agg/asa1 - 38.4%, ace/acm - 64.3%, efaA - 85.9%, eep - 69.4%, gelE - 64.3%, hyl - 25.1%, and cylA - 47.1%. E. faecalis isolates had significantly higher frequency of adhesin genes (esp and agg/asa1) and gelatinase in comparison to E. faecium. Multiple virulence genes in E. faecalis were significantly more prevalent than in E. faecium isolates. Domination of E. faecium with or without only one gene compared to the isolates of E. faecalis were found. Enterococcus spp. isolates obtained from outpatients compared to inpatients isolates had significantly higher frequency of agg/asa1, eep, gelE and cylA. Some adhesins genes (esp, agg/asa1 and efaA) had higher prevalence among the non-invasive Enterococcus spp. isolates compared to those causing invasive bacteremia, while ace/acm revealed higher dissemination in isolates causing invasive infections compared to non-invasive isolates.ConclusionMost E. faecalis attaches to abiotic surfaces in hospital environment, which correlates with higher prevalence of gene encoding for virulence factors involved in biofilm formation, such as enterococcal surface protein, aggregation substance, and gelatinase. The intestinal tract is an important reservoir for opportunistic enterococcal pathogens and allows them to access infectious sites through different virulence factors, demonstrated in outpatient isolates in this study.
| S-EPMC9427613 | biostudies-literature
Project description:Enterococcus faecalis is a Gram-positive, facultative anaerobic bacterium frequently found in the gastrointestinal tract, oral cavity, and periodontal tissue. Although it is considered a commensal, it can cause bacteremia, endocarditis, endodontic infections, and urinary tract infections. Because antibiotics are cytotoxic not only to pathogens, but also to health-beneficial commensals, phage therapy has emerged as an alternative strategy to specifically control pathogenic bacteria with minimal damage to the normal flora. In this study, we isolated a novel phage, Enterococcus phage vB_EfaS_HEf13 (phage HEf13), with broad lytic activity against 12 strains of E. faecalis among the three laboratory strains and 14 clinical isolates of E. faecalis evaluated. Transmission electron microscopy showed that phage HEf13 has morphological characteristics of the family Siphoviridae. Phage HEf13 was stable at a wide range of temperature (4-60°C) and showed tolerance to acid or alkaline (pH 3-12) growth conditions. Phage HEf13 had a short latent period (25 min) with a large burst size (approximately 352 virions per infected cell). The lytic activity of phage HEf13 at various multiplicities of infection consistently inhibited the growth of diverse clinical isolates of E. faecalis without any lysogenic process. Moreover, phage HEf13 showed an effective lytic activity against E. faecalis on human dentin ex vivo infection model. Whole genome analysis demonstrated that the phage HEf13 genome contains 57,811 bp of double-stranded DNA with a GC content of 40.1% and 95 predicted open reading frames (ORFs). Annotated functional ORFs were mainly classified into four groups: DNA replication/packaging/regulation, phage structure, host cell lysis, and additional functions such as RNA transcription. Comparative genomic analysis demonstrated that phage HEf13 is a novel phage that belongs to the Sap6virus lineage. Furthermore, the results of multiple sequence alignment showed that polymorphism of phage infection protein of E. faecalis (PIPEF) contributes to determine the host specificity of phage HEf13 against various E. faecalis strains. Collectively, these results suggest that phage HEf13 has characteristics of a lytic phage, and is a potential therapeutic agent for treatment or prevention of E. faecalis-associated infectious diseases.
| S-EPMC6927925 | biostudies-literature
Project description:Enterococcus faecalis is a Gram-positive bacterium that is a major cause of hospital-acquired infections, in part due to its intrinsic resistance to cephalosporins. The mechanism that confers intrinsic cephalosporin resistance in enterococci remains incompletely defined. Previously, we have shown that the Ser/Thr protein kinase and phosphatase pair IreK and IreP act antagonistically to regulate cephalosporin resistance in E. faecalis. We hypothesize that IreK senses antibiotic-induced cell wall damage and activates a signaling pathway leading to antibiotic resistance. However, the factors downstream of IreK have not yet been identified. To discover such factors, suppressor mutations that restored resistance to a ?ireK kinase mutant were identified. Mutations were found in IreB, a highly conserved gene of unknown function that is widespread among low-GC Gram-positive bacteria. We show that IreB plays a negative regulatory role in cephalosporin resistance and is an endogenous substrate of both IreK and IreP. IreB is phosphorylated on conserved threonine residues, and mutations at these sites impair cephalosporin resistance. Our results are consistent with a model in which the activity of IreB is modulated by IreK-dependent phosphorylation in a signaling pathway required for cephalosporin resistance and begin to shed light on the function of this previously uncharacterized protein.
| S-EPMC3837872 | biostudies-literature