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PubMed2026

Convergent evolution of immune evasion in ESKAPE pathogens: A cross-pathogen architecture of conserved host-defense checkpoints.

Antimicrobial resistance in ESKAPE pathogens is primarily attributed to resistance genes, yet persistent infections despite appropriate therapy implicate immune evasion as an independent driver of treatment failure. Although immune-evasion mechanisms have been extensively characterized in individual pathogens, their shared architecture across the ESKAPE group remains insufficiently integrated. This review synthesizes current evidence to show that phylogenetically diverse ESKAPE pathogens have convergently evolved conserved strategies to evade host immunity under comparable selective pressures. A cross-pathogen immune-evasion framework emerges, encompassing impaired pathogen recognition, complement inhibition, phagocyte dysfunction, immunometabolic reprogramming, biofilm-mediated protection, and persistence-promoting inflammation, together with pathogen-specific virulence mechanisms. These processes intersect with adaptive immune dysfunction and emerging concepts, including quorum-sensing-mediated immunomodulation, trained immunity, and the itaconate-succinate immunometabolic axis, forming an interconnected persistence network rather than isolated virulence traits. This systems-level perspective identifies conserved host-directed therapeutic targets that may complement conventional antimicrobial therapy across species. However, host-directed therapies, immunotherapeutics, and vaccines remain largely preclinical or have shown inconsistent clinical efficacy. Mechanistic evidence is strongest for Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, whereas substantial knowledge gaps persist for Enterococcus faecium, Acinetobacter baumannii, and Enterobacter spp. Overcoming persistent ESKAPE infections will require targeting conserved host-pathogen interactions alongside pathogen-specific antimicrobial resistance mechanisms.

Convergent immune evasion↗
PubMed2026

Systematic review on genomic insights into antimicrobial resistance in ESKAPE pathogens.

BACKGROUND: Antimicrobial resistance (AMR) is a major global public health threat. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a major threat owing to resistance to last-line antibiotics. Genomic surveillance is crucial to understanding global and regional antimicrobial resistance genes (ARGs) in AMR transmission. AIM: This systematic review synthesised global genomic evidence to identify global and region-specific ARGs distribution among ESKAPE pathogens. METHODS: Following PRISMA guidelines, studies published January 2019 to December 2024 were identified from PubMed, Google Scholar, and Web of Science. Eligible studies reported genomic characteristics and resistance patterns of one or more ESKAPE pathogens from any source. RESULTS: Seventy-seven studies were included, with most originating from Asia, followed by Europe and Africa. Clinical isolates predominated K. pneumoniae was the most frequently investigated pathogen, followed by S. aureus, P. aeruginosa, and A. baumannii. The most reported resistance genes were blaCTX-M, blaNDM, and blaSHV. Distinct regional patterns of antimicrobial resistance gene (ARG) distribution were observed, with tetracycline and quinolone resistance genes prevailing in Africa and South America, and blaOXA variants dominating in Asia and Europe. Region-specific ARG patterns were identified through descriptive synthesis and comparative analysis of study-reported frequencies. CONCLUSION: This review provides a synthesised global map of ARG distribution in ESKAPE pathogens, highlighting surveillance gaps in underrepresented regions and non-clinical settings. Addressing these gaps will support targeted genomic surveillance and stewardship programmes. WHAT THIS STUDY ADDS: This study contributes to the body of knowledge by mapping global and regional antimicrobial resistance gene patterns in ESKAPE pathogens, identifying key surveillance gaps and informing targeted AMR monitoring and stewardship strategies.

ESKAPE pathogens↗
PubMed1977

Teichoic acids of group D streptococci with special reference to strains from pig meningitis (Streptococcus suis).

Immunoelectrophoresis revealed in phenol extracts from S. faecalis and S. faecium a mixture of free and lipid-bound teichoic acids, both reactive with Group D antisera. In phenol extracts from S. suis only lipid-bound teichoic acid, also reactive with Group D antiserum, was seen. This difference probably accounts for the low yield of Group D antigen from S. suis as compared with S. faecalis and S. faecium when heating at pH 2 is used for extraction. When phenol is used good yields are obtained from S. suis as well as from S. faecalis and S. faecium. Lipoteichoic acids from S. faecalis and S. faecium have a backbone structure the same as or similar to that of Group A streptococcal teichoic acid. Lipoteichoic acid from S. suis has a structure differing from that of S. faecalis and S. faecium, e.g., possibly in the attachment of its glucosyl substituents. Precipitation reactions between S. suis lipoteichoic acid and Group D antisera were specifically inhibited by glucose. Reactions between S. bovis phenol extracts and some Group D antisera were also specifically inhibited by glucose, but extracts from S. faecalis and S. faecium were not. This may indicate a monosaccharide glucosyl substituent in teichoic acid from S. suis and S. bovis instead of the di- or trisaccharide previously postulated as the glucosyl substituent in the teichoic acid of S. faecalis.

Animals↗
PubMed2025

Potential biomarkers for human Ascending aortic aneurysm identified through metagenomic and metabolomic analyses: A case-control study.

INTRODUCTION: Ascending aortic aneurysm (AsAA) is a high-risk cardiovascular condition; recent research indicates a possible association between gut microbiota, plasma metabolites, and the pathogenesis of AsAA. OBJECTIVE: This study aims to investigate the compositional and metabolic alterations in the gut microbiota of AsAA patients to identify potential biomarkers for AsAA. METHODS: This study enlisted 72 participants, comprising 44 individuals with AsAA and 28 healthy controls. All participants underwent examination for clinical features, and fecal and plasma samples were obtained for metagenomic and metabolomic studies. RESULTS: Metagenomic analysis revealed a significant reduction of 23 bacterial species in AsAA patients, including Bifidobacterium adolescentis, Bifidobacterium longum, Lactiplantibacillus plantarum, Enterococcus faecalis, and Streptococcus thermophilus, while 52 bacterial species, such as Prevotella copri, Phascolarctobacterium faecium, and Eubacterium ventriosum, were found to be enriched. Furthermore, we identified seven microbial co-abundance groups (CAGs), of which three (predominantly comprising Roseburia, Agathobacter, and Prevotella) were significantly elevated in AsAA patients, whereas one (predominantly comprising Escherichia) was substantially diminished. KEGG pathway enrichment analysis indicated that the biosynthesis of unsaturated fatty acids pathway displayed the most pronounced differences between groups. Metabolomics data revealed that 22 metabolites, including ceramides, were significantly elevated, while 8 metabolites, such as threonine, were notably downregulated. Moreover, clinical indicators like C-reactive protein (CRP) and complement components C3 and C4 have shown strong correlations with specific gut microbiota (Streptococcus, Prevotella) and plasma metabolites (threonine, ceramides). These findings indicate that inflammatory responses, metabolic dysregulation, and gut microbiota imbalance are pivotal in the etiology of AsAA. CONCLUSION: This study demonstrates substantial alterations in gut microbiota composition and plasma metabolites in patients with AsAA. Prevotella and ceramides exhibit potential as biomarkers for AsAA diagnosis. Furthermore, a synergy of Prevotella and ceramides may function as a potent disease prediction classifier, offering novel perspectives on the early diagnosis and targeted treatment of AsAA.

Humans↗
PubMed1979

[Lactic acid bacteria and streptococci of the human stomach normally and in pathological processes].

Lactic acid bacteria were either absent or present in negligent quantities in the stomach of apparently healthy man. But in case of various pathological processes in the stomach and duodenum lactic acid bacteria accumulated (up to a million cells per 1 ml of gastric contents). Under these conditions coccal forms sharply prevailed over the bacillary ones. In patients with chronic gastritis and peptic ulcer of the stomach the most frequent were Streptococcus faecalis and its variants; in oncological patients--Str. faecium, strains affiliated to Leuconostoc mesenteroides, and sometimes Str. durans.

Adult↗
PubMed1979

Untyped forms of faecal streptococci in Egyptian sewage and Nile water.

When the thallous-azide agar medium was used a higher incidence of pure faecal streptococci recovery was recorded especially from slightly polluted vehicles such as river water than on the standard M-enterococcus agar medium. In addition, a thallous-azide combination at pH 6.5 was used successfully for the primary isolation of Str. faecalis and its two variants. Results of biochemical tests of 274 faecal streptococci isolates showed that 20% belonged to Str. faecalis and its two variants as well as Str. durans, Str. faecium and Str. equinus. Thirty-eight percent of the isolated strains were classified as atypical I, II, III, and V previously designated by COOPER and RAMADAN (1955) as well as the unclassified group of RAMADAN et al. (1972). While the remaining 42% were found to belong to seven different categories (SALEH 1976 and 1977). The correlation between four differential tests used for defining the source of faecal streptococci isolates was discussed.

Egypt↗
PubMed2026

Emergence of an optrA-positive Enterococcus faecalis ST699 lineage in animal-derived foods in Beijing, China.

Enterococci from animal-derived foods are key reservoirs for antimicrobial resistance (AMR) in the food chain. However, comparative genomic studies investigating the distribution of the oxazolidinone resistance gene optrA among food- and human-derived Enterococci remain limited. This study assessed linezolid-resistant Enterococci from retail meat and healthy humans in Beijing, China (2023-2024). Among 87 isolates, E. faecalis and E. faecium predominated. Food-derived isolates showed broader resistance profiles than human isolates. Fourteen optrA-positive strains were identified, accounting for 92.9% of food isolates. optrA frequently co-localized with erm(A), ant(9)-Ia, and fexA on Tn554-family transposons, suggesting a potentially transferable multidrug resistance module. Notably, an optrA-positive E. faecalis ST699 clone was identified for the first time in Chinese retail meat. This clone formed a distinct lineage and carried a complete Tn554-optrA island. A representative ST699 isolate exhibited enhanced fitness and virulence potential in the Galleria mellonella model. These findings highlight animal-derived foods as important reservoirs of linezolid-resistant Enterococci and provide genomic evidence consistent with their role as potential sources of optrA-mediated resistance. The emergence of a multidrug-resistant E. faecalis ST699 clone with enhanced fitness characteristics underscores the need for continued surveillance of foodborne antimicrobial resistance within the One Health framework.

Enterococcus faecalis↗
PubMed1978

Relationship between cellular autolytic activity, peptidoglycan synthesis, septation, and the cell cycle in synchronized populations of Streptococcus faecium.

Synchronized, slowly growing (TD = 70 to 80 min) cultures were used to study several wall-associated parameters during the cell cycle: rate of peptidoglycan synthesis, septation, and cellular autolytic activity. The rate of peptidoglycan synthesis per cell declined during most of the period of chromosome replication (C), but increased during the latter part of C and into the period between chromosome termination and cell division (D). An increase in cellular septation was correlated with the increased rate of peptidoglycan synthesis. Cellular autolytic capacity increased during the early portion of C, reached a maximum late in C or early in D, and declined during D. Inhibition of DNA synthesis during C prevented the decline in autolytic capacity at the end of the cell cycle, caused a slight reduction in the rate of peptidoglycan synthesis, delayed but did not prevent septation, and prevented the impending cell division by inhibiting cell separation. Inhibition of DNA synthesis during D did not prevent the increase in autolytic capacity during the next C phase, but, once again, prevented the decline at the end of the subsequent cycle. Thus, increased autolytic capacity at the beginning of the cell cycle did not seem to be related to chromosome initiation, whereas decreased autolytic capacity at the end of the cell cycle seemed to be related to chromosome termination. The data presented are consistent with the role of autolytic enzyme activity in the previously proposed model for cell division of S. faecium (G.D. Shockman et al., Ann. N.Y Acad. Sci. 235:161-197, 1974).

Cell Cycle↗
PubMed1978

Characterization of plasmids in bacteriocin producing strains of Streptococcus faecium.

Four bacteriocin (enterocin) producing strains of Streptococcus faecium were examined for extrachromosomal DNA. Three strains proved to harbor minicircular plasmid DNA of uniform length as evidenced by CsCl ethidium bromide density centrifugation and electron microscopy. Molecular weight determination obtained through contour length measurements showed 2.4 X 10(6) dalton for S. faecium 25, 3.4 X 10(6) dalton for S. faecium 3 and 3.8 X 10(6) dalton for S. faecium 59. Elimination experiments for bacteriocin production with intercalating dyes proved sterile. The role of these plasmids remains for the time being unknown.

Anti-Bacterial Agents↗
PubMed1979

The distribution of isoprenoid quinones in streptococci of serological groups D and N.

The isoprenoid quinone contents of streptococci of serological groups D and N were investigated. Streptococcus faecalis, S. faecalis subsp. liquefaciens and S. faecalis subsp. zymogenes strains contained demethylmenaquinones with nine isoprene units as their major isoprenologues. Menaquinones with eight isoprene units predominated in S. faecium subsp. casseliflavus and S. faecium subsp. mobilis whereas menaquinones with nine isoprene units constituted the major components in strains of S. cremoris, S. cremoris subsp. alactosus, S. lactis and S. lactis subsp. diacetylactis. Strains of S. avium, S. bovis, S. durans, S. equinus, S. faecium, S. raffinolactis and S. suis contained neither menaquinones nor ubiquinones. The isoprenoid quinone data correlate well with other kinds of data on these organisms and are of value in the classification of these bacteria.

Enterococcus faecalis↗
PubMed2026

Novelty, diversity, and genetic dark matter in enterococci of invertebrates.

Enterococci appear to have originated in the guts of early terrestrializing arthropods and invertebrates over 425 million years ago-hosts that are now highly diverse and widespread in nature today. Yet most knowledge of the genus comes from human infection-associated lineages with genomes swollen by the recent accretion of foreign DNA conveyed by mobile elements. Because invertebrates dominate terrestrial animal diversity and biomass, they would be predicted to constitute a major but little-explored reservoir of enterococcal diversity. We therefore systematically examined Enterococcus association and species diversification in invertebrate hosts of the comparatively natural, isolated, but well-characterized environment of the Azorean island of Terceira. Over 100 invertebrate specimens were examined for associated enterococci, which were taxonomically classified by whole-genome sequencing. Supporting the existence of a large pool of uncharacterized enterococci and Enterococcus-adapted genes, 40% (eight of 20) of the Enterococcus species identified were either undescribed, including four candidate new species described here, or very recently discovered. In contrast, control isolates from vertebrates were exclusively of known species typical of sampling elsewhere, discounting geographic isolation as a main driver of the novelty observed. Further, because of the abundance of E. casseliflavus and E. flavescens in this collection, we obtained the resolution necessary to quantify the divergence and decipher the drivers of speciation in the controversial division between these naturally vancomycin-resistant species. These findings provide robust support for the existence of a large pool of new species and unexplored adaptive traits in invertebrate-associated enterococci-diverse environmental survival traits optimized for expression in an enterococcal background, and well positioned for transmission into human-associated enterococcal strains.IMPORTANCEEnterococci are auxotrophic gut-associated bacteria that co-evolved with their terrestrial hosts over many eons. In the last 75 years-the "antibiotic era"-E. faecalis and E. faecium gained genes for antibiotic resistance and enhanced virulence, emerging as leading causes of multidrug-resistant infection. Little is known about the source of those genes or the pathway by which they entered human-associated strains. A recent global survey suggested a potentially large repository of uncharacterized genetic diversity in the enterococci of invertebrates. We directly tested this prospect by examining enterococci of invertebrate hosts in a largely natural and pastoral environment. Our findings provide clear evidence that invertebrates naturally harbor vast unexplored enterococcal diversity. Moreover, associations are likely driven by intrinsic host selection factors rather than geographic isolation. This expands our knowledge of Enterococcus biodiversity, including the identification of four novel species, identifying a vast reservoir of enterococcal genes available to species that colonize and infect humans.

Animals↗
PubMed1979

Species-specific resistance to antimocrobial synergism in Streptococcus faecium and Streptococcus faecalis.

Combinations of penicillin with various aminoglycosidic aminocyclitols were tested against a collection of clinical isolates of Streptococcus faecium in vitro and were used to treat endocarditis caused by S. faecium in the rabbit model. S. faecium proved more resistant to penicillin than Streptococcus faecalis. Even more striking, however, was the resistance to in vitro synergism by combinations of penicillin and various aminoglycosides. At clinically achievable concentrations, penicillin-gentamicin was the only combination that was synergistic against all strains that were tested. Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin, respectively. Combinations of penicillin with kanamycin, tobramycin, sisomicin, or netilmicin failed to produce synergism against any of these strains. The possible clinical significance of these findings was verified by use of the rabbit model of endocarditis. Combinations of penicillin with gentamicin or streptomycin were synergistic in the therapy of endocarditis that was produced by a strain of S. faecium that did not have a high level of resistance to aminoglycosides. However, the combination of penicillin and netilmicin was no more effective than penicillin alone.

Aminoglycosides↗
PubMed1978

Carriage of group D streptococci in the human bowel.

Sixty faecal samples, 39 from adults and 21 from neonates, were investigated by means of a simple scheme to isolate and identify any group D streptococci present. A number of differences were found between the two groups. Group D streptococci were absent from 43% of the neonates compared with only 13% of the adults; Streptococcus bovis was commoner in the neonates (23.8%) than in the adults (5%), and Streptococcus faecium was not isolated from any of the infant samples although it was common in the adult samples (25%). The viable counts of Strep. faecium were found to be, on average, 100-fold lower than those of Streptococcus faecalis. The methods and results are discussed with reference to the clinical significance of group D streptococci, especially in bacterial endocarditis and carcinoma of the colon.

Adult↗
PubMed1978

Use of pyruvate fermentation compared with tetrazolium reduction in the differentiation of group D streptococci.

The reduction of 2, 3, 5 triphenyltetrazolium chloride in the original medium of Barnes (Journal of General Microbiology, 14, 57, 1956), and in a modified medium, was compared with the ability to ferment pyruvate as a means of separating Streptococcus faecalis from all other group D streptococci. The tetrazolium reduction test gave an occasional negative reaction with Str. faecalis strains. In addition, a number of strains gave a weakly positive reaction in the test, as did some strains of Str. faecium and Str. bovis. With some batches of tetrazolium, these weak reactions with Str. faecalis were so frequent that interpretation of the results was difficult. On the other hand, all Str. faecalis strains, and no other group D streptococci, gave a positive pyruvate-fermentation reaction in 48 hours.

Bacteriological Techniques↗
PubMed1979

Effects of cerulenin on antibiotic-induced lysis of streptococcus faecalis (S. faecium).

Addition of the antibiotic cerulenin to cultures lowered the minimal effective concentration of penicillin G or methicillin required to produce bacterial lysis and killing. This effect was most pronounced at subinhibitory antibiotic concentrations. Cerulenin had no significant effects on lysis or killing induced in the presence of D-cycloserine, fosfomycin, bacitracin, or vancomycin.

Anti-Bacterial Agents↗
PubMed1978

Incidence and relationship of group D streptococci with other indicator organisms in meats.

Raw and processed meats were analyzed for presumptive group D streptococci using KF streptococcus agar. Counts were compared with coliform, presumptive Escherichia coli, and Enterobacteriaceae counts but no meaningful relationships were observed. Results indicated that group D streptococci and E. coli type I were principally contaminants from the packing plant, rather than at retail level. The predominating group D streptococcus in both beef and pork cuts was Streptococcus faecalis, while in processed meat (bologna), the predominating group D streptococci were Streptococcus faecium var. durans and Streptococcus faecium. Streptococcus bovis was not detected among the isolates from any meat samples. Marked differences were noted in numbers of group D streptococci in processed meat from different manufacturers. The results did not support the use of group D streptococci as alternative indicator organisms for meats. However, the association of group D streptococci with packing plant contamination may prove to be of value.

Animals↗
PubMed1978

[The etiology of foul brood].

Five hundred and thirty-six samples of honeycombs were examined in a laboratory in the years 1971-1974. In all the samples clinically determined as the foul brood, B. alvei was isolated as a pure culture, and enterococci, or both microorganisms were isolated in mixed form. Twenty-five strains of the isolated streptococci were analyzed microbiologically and biochemically; on the basis of their culture and biochemical characteristics five strains were designated as Streptococcus faecalis, 14 strains as Streptococcus faecalis var. liquefaciens, five strains as Streptococcus faecium and one strain as Streptococcus durans. After checking the used taxonomic key of the culture and biochemical classification of B. alvei it may be stated that the culture and biochemical characteristics are stable. The strains of B. alvei (very dried strains), which persisted in the dried slant meat-peptone agar, were viable under the laboratory conditions, which proves the high resistance of the spores to the environment.

Animals↗