Enterococci facilitate polymicrobial infections

Xu, Wenjiao; Fang, Yuwen; Zhu, Kui

doi:10.1016/j.tim.2023.07.010

Cited by 8 publications

(6 citation statements)

References 101 publications

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“…Given the propensity of E. faecalis to contribute to polymicrobial infections ( Xu et al, 2024 ), our focus shifted to evaluating CHU-1’s efficacy against both A. baumannii and E. faecalis , as well as their potential coinfection. Initially, we investigated whether CHU-1 treatment resulted in increased permeabilization of the plasma membrane.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, Acinetobacter baumannii complex (ABC) infections often manifest as polymicrobial infections ( Karakonstantis et al, 2022 ). Of particular concern is coinfection with Enterococci , which complicates pathogenesis, worsens prognoses, and undermines the efficacy of antimicrobial agents by fostering the colonization, proliferation, and persistence of various pathogenic bacteria ( Xu et al, 2024 ). Therefore, addressing the therapeutic challenges posed by polymicrobial infections of ESKAPEE is of paramount importance and combinatorial therapies or innovative antimicrobial agents are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against “ESKAPEE” pathogens

Chen,

Han,

Chen

et al. 2024

Front. Microbiol.

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The rise of antimicrobial resistance in ESKAPEE pathogens poses significant clinical challenges, especially in polymicrobial infections. Bacteriophage-derived endolysins offer promise in combating this crisis, but face practical hurdles. Our study focuses on engineering endolysins from a Klebsiella pneumoniae phage, fusing them with ApoE23 and COG133 peptides. We assessed the resulting chimeric proteins’ bactericidal activity against ESKAPEE pathogens in vitro. ApoE23-Kp84B (CHU-1) reduced over 3 log units of CFU for A. baumannii, E. faecalis, K. pneumoniae within 1 h, while COG133-Kp84B (CHU-2) showed significant efficacy against S. aureus. COG133-L1-Kp84B, with a GS linker insertion in CHU-2, exhibited outstanding bactericidal activity against E. cloacae and P. aeruginosa. Scanning electron microscopy revealed alterations in bacterial morphology after treatment with engineered endolysins. Notably, CHU-1 demonstrated promising anti-biofilm and anti-persister cell activity against A. baumannii and E. faecalis but had limited efficacy in a bacteremia mouse model of their coinfection. Our findings advance the field of endolysin engineering, facilitating the customization of these proteins to target specific bacterial pathogens. This approach holds promise for the development of personalized therapies tailored to combat ESKAPEE infections effectively.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against “ESKAPEE” pathogens

Chen,

Han,

Chen

et al. 2024

Front. Microbiol.

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“…It is highly related to mucosal inflammation and bile acid metabolism and can improve the content of regulatory T cells and the production of short-chain fatty acids [ 30 , 31 ]. Enterococci are Gram-positive cocci that occur singly, in pairs, or in short chains and have a fermentative metabolism in which they convert carbohydrates to lactic acid [ 31 , 32 ]. Enterobacter bacteria are motile, rod-shaped cells and possess peritrichous flagella.…”

Section: Discussionmentioning

confidence: 99%

“…Enterococci are Gram-positive cocci that occur singly, in pairs, or in short chains and have a fermentative metabolism in which they convert carbohydrates to lactic acid [31,32]. Enterobacter bacteria are motile, rod-shaped cells and possess peritrichous flagella.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota was highly related to the immune status in chronic obstructive pulmonary disease patients

Wang,

Song,

Yang

et al. 2024

Aging

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This study aimed to explore the profile of gut microbiota and immunological state in COPD patients. 80 fecal and blood samples were collected from 40 COPD patients and 40 healthy controls (HC) and analyzed with 16s-rRNA gene sequencing and immunofactor omics analysis to investigate the profile of gut microbiota and immunologic factors (IFs). The linear discriminant analysis (LDA) effect size (LefSe) was used to determine the biomarker’s taxa. The random forest and LASSO regression analysis were executed to screen IFs and develop an IFscore model. The correlation between gut microbiota and IFs, along with the IFscore and the diversity of gut microbiota, was evaluated with the Spearman analysis. The α and β diversity showed that the composition and distribution of gut microbiota in the COPD group differed from that of the HC group. 7 differential taxa at the phylum level and 17 differential taxa at the genus level were found. LefSe analysis screened out 5 biomarker’s taxa. 32 differential IFs (up-regulated 27 IFs and down-regulated 5 IFs) were identified between two groups, and 5 IFs (CCL3, CXCL9, CCL7, IL2, IL4) were used to construct an IFscore model. The Spearman analysis revealed that 29 IFs were highly related to 5 biomarker’s taxa and enriched in 16 pathways. Furthermore, the relationship between the IFscore and gut microbiota diversity was very close. The gut microbiota and IFs profile in COPD patients differed from that in healthy individuals. Gut microbiota was highly related to the immune status in COPD patients.

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“…Many factors can favor the overgrowth of enterococci in the gut, including medical reasons, dietary habits, and susceptible individuals [ 1 ]. Enterococcal intestinal domination, especially the devastating dissemination of vancomycin-resistant enterococci, has been identified as an indicator of subsequent infections and adverse outcomes [ 2 , 3 ]. Numerous studies demonstrated that enterococci facilitate the growth and pathogenicity of various pathogens, such as Clostridioides difficile , Staphylococcus aureus , Pseudomonas aeruginosa , Escherichia coli , Gardnerella vaginalis , and Candida albicans , via up-regulation of virulence, metabolic cross-feeding, biofilm formation, immune evasion, and transmission of drug resistance [ 4 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Coumarin Glycosides Reverse Enterococci-Facilitated Enteric Infections

Xu,

Yuan,

Fang

et al. 2024

Research

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Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium ( S . Tm). Subsequently, we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo. Enterococci, which are tolerant of iron-deficient environments, produce β-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones, inhibiting S . Tm growth and ameliorating the severity of S . Tm-induced symptoms by inducing iron limitation. Overall, we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections, providing an alternative intervention to combat polymicrobial infections.

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Enterococci facilitate polymicrobial infections

Cited by 8 publications

References 101 publications

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against “ESKAPEE” pathogens

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against “ESKAPEE” pathogens

Gut microbiota was highly related to the immune status in chronic obstructive pulmonary disease patients

Coumarin Glycosides Reverse Enterococci-Facilitated Enteric Infections

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