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1.
  • Qiu, Bo, et al. (author)
  • Enhanced gut microbiota delivery of a model probiotic (Faecalibacterium prausnitzii) : Layer-by-layer encapsulation using riboflavin-conjugated sodium alginate and glycol chitosan
  • 2024
  • In: Food Hydrocolloids. - : Elsevier. - 0268-005X .- 1873-7137. ; 154
  • Journal article (peer-reviewed)abstract
    • Faecalibacterium prausnitzii (F. prausnitzii) exhibits a variety of biological functions that make it suitable for use as a next-generation probiotic. However, its high sensitivity to oxygen and digestive fluids currently limits its application. Riboflavin is known to support the growth of F. prausnitzii in oxygen environments, but it is important that it is in close proximity to the probiotics. Layer-by-layer assembly can be used to form protective coatings around probiotics, which can protect them from adverse environmental conditions. Moreover, riboflavin can be conjugated to these coatings, thereby increasing its efficacy by bringing it close to probiotic surfaces. In this study, we therefore evaluated the potential of electrostatic layer-by-layer assembly to protect F. prausnitzii by coating them with riboflavin-alginate and glycol-chitosan layers. Initially, we showed that riboflavin could be successfully conjugated to alginate, with a grafting ratio of around 4.35%. Then, the layer-by-layer method was used to coat F. prausnitzii using cationic glycol chitosan and anionic riboflavin-alginate. The coating formed was found to have a thickness of approximately 18.5 nm. Encapsulation did not adversely affect the growth of F. prausnitzii, but it significantly enhanced its resistance to oxygen and digestive fluids. The encapsulated probiotic was shown to have enhanced mucoadhesive properties using an in vitro intestinal monolayer model. Furthermore, the encapsulated probiotics colonized the colons of rats for longer than nonencapsulated ones. These results show that coating F. prausnitzii with riboflavin-rich biopolymer layers improves its resistance to oxygen and digestive fluids, and enhances its mucoadhesion and colonization properties, which should enhance its potential as an orally administered probiotic.
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2.
  • Fei, Yiqiu, et al. (author)
  • Role of prebiotics in enhancing the function of next-generation probiotics in gut microbiota
  • 2023
  • In: Critical reviews in food science and nutrition. - : TAYLOR & FRANCIS INC. - 1040-8398 .- 1549-7852. ; 63:8, s. 1037-1054
  • Research review (peer-reviewed)abstract
    • With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.
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3.
  • Wang, Di, et al. (author)
  • High prevalence of Escherichia coli co-harboring conjugative plasmids with colistin- and carbapenem resistance genes in a wastewater treatment plant in China
  • 2023
  • In: International journal of hygiene and environmental health. - : Elsevier. - 1438-4639 .- 1618-131X. ; 250
  • Journal article (peer-reviewed)abstract
    • Emergence and dissemination of resistance to last-resort antibiotics such as carbapenem and colistin is a growing, global health concern. Wastewater treatment plants (WWTPs) link human activities and the environment, can act as reservoirs and sources for emerging antibiotic resistance, and likely play a large role in antibiotic resistance transmission. The aim of this study was to investigate occurrence and characteristics of colistin-and carbapenem-resistant Escherichia coli (CCREC) in wastewater and sludge samples collected over a one-year period from different functional areas of an urban WWTP in Jinan city, Shandong, China. A total of 8 CCREC were isolated from 168 samples with selective agar and PCR, corresponding to high prevalence of 4.8%, co-harboring car-bapenem resistance genes (blaNDM) and colistin resistance gene (mcr-1) and subsequently whole-genome sequenced. Additionally, all isolates were multidrug-resistant by antimicrobial susceptibility testing and car-ried a variety of antibiotic resistance genes. Two isolates carrying virulence genes associated with avian path-ogenic E. coli were identified, one belonging to the high-risk clone O101:H9-ST167. Southern blotting was used to characterize CCREC isolates and plasmids carrying blaNDM-genes or mcr-1 could be transferred to a recipient strain E. coli J53 by in vitro conjugation assays. Resistance to other antibiotic classes were sporadically co-transferred to the transconjugant. Transposition of and mcr-1-carrying element from a transferable IncHI2-plasmid was observed among two CCREC clones isolated within 4 days of each other. The occurrence of multidrug-resistant CCREC capable of transferring their antibiotic resistance genotypes via conjugative plasmids is alarming. WWTPs bring bacteria from different sources together, providing opportunities for horizontal ex-change of DNA among compatible hosts. Further dissemination of the colistin-, carbapenem-, or both colistin-and carbapenem resistant E. coli could lead to a serious threat to public health.
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4.
  • Wang, Di, et al. (author)
  • Transmission of clones of carbapenem-resistant Escherichia coli between a hospital and an urban wastewater treatment plant*
  • 2023
  • In: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 336
  • Journal article (peer-reviewed)abstract
    • Carbapenem-resistant Enterobacterales (CRE) constitute an urgent threat to worldwide public health. The spread of CRE is facilitated by transmission via the environment. Wastewater treatment plants (WWTPs) are considered to be important sources of antibiotic resistance and hot spots of antibiotic-resistant bacteria (ARB) which can facilitate dissemination of antibiotic resistance genes. In this study, water samples were collected over one year from a WWTP in Jinan, Shandong province, China, from different functional sites in the wastewater treatment process. Carbapenem-resistant Escherichia coli (CREC) were isolated by selective cultivation and whole-genome sequenced to investigate the occurrence and characteristics of CREC in the WWTP. A total of 77 CREC isolates were included in the study and the detection rate of CREC in the WWTP water inlet was found to be 85%. An additional 10 CREC were isolated from a nearby teaching hospital during the sampling period and included for comparison to the environmental isolates. Susceptibility testing showed that all CREC were multidrug-resistant. 6 different carbapenem resistance genes (CRGs) were detected, including blaNDM-5 (n = 75), blaNDM-1 (n = 6), blaNDM-4 (n = 3), blaNDM-6 (n = 1), blaNDM-9 (n = 1), and blaKPC-2 (n = 4). 42 CREC isolates were whole-genome sequenced with Illumina short-read sequencing. 11 of these were also sequenced with Nanopore long-read sequencing. Plasmids carrying CRGs were found to belong to IncX3 (n = 35), IncFII (n = 12), IncFIA (n = 5), IncFIB (n = 2), IncC (n = 1), and IncP6 (n = 1). Clonal dissemination of CREC belonging to ST167, ST448, and ST746 was observed between different parts of the WWTP. Furthermore, isolates from the WWTP, including an isolate belonging to the high-risk ST167 strain, were found to be clonally related to CREC isolated at the hospital. The spread of CRGs is of considerable concern and strategies to prevent environmental dissemination of this contaminant urgently needs to be implemented.
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5.
  • Zou, Huiyun, et al. (author)
  • Persistent transmission of carbapenem-resistant, hypervirulent Klebsiella pneumoniae between a hospital and urban aquatic environments
  • 2023
  • In: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 242
  • Journal article (peer-reviewed)abstract
    • The increasing prevalence of infections caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae strains (CR-hvKP) prompts the question of whether these strains also circulate outside of clinical settings. However, the environmental occurrence and dissemination of CR-hvKP are poorly studied. In the current study, we investigated the epidemiological characteristics, and dissemination dynamics of carbapenem-resistant K. pneumoniae (CRKP) isolated from a hospital, an urban wastewater treatment plant (WWTP), and adjacent rivers in Eastern China during one year of monitoring. A total of 101 CRKP were isolated, 54 were determined to be CR-hvKP harboring pLVPK-like virulence plasmids, which were isolated from the hospital (29 out of 51), WWTP (23 out of 46), and rivers (2 out of 4), respectively. The period with lowest detection rate of CR-hvKP in the WWTP, August, corresponded with the lowest detection rate at the hospital. Comparing the inlet and outlet of the WWTP, no significant reduction of the detection of CR-hvKP and relative abundance of carbapenem resistance genes was observed. The detection rate of CR-hvKP and the relative abundance of carbapenemase genes were significantly higher in the WWTP in colder months compared to warmer months. Clonal dissemination of CR-hvKP clones of ST11-KL64 between the hospital and the aquatic environment, as well as the horizontal spread of IncFII-IncR and IncC plasmids carrying carbapenemase genes, was observed. Furthermore, phylogenetic analysis showed that the ST11-KL64 CR-hvKP strain has spread nationally by interregional transmission. These results indicated transmission of CR-hvKP clones between hospital and urban aquatic environments, prompting the need for improved wastewater disinfection and epidemiological models to predict the public health hazard from prevalence data of CR-hvKP.
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6.
  • Chen, Baoli, et al. (author)
  • Rapid increase in occurrence of carbapenem-resistant Enterobacteriaceae in healthy rural residents in Shandong Province, China, from 2015 to 2017
  • 2022
  • In: Journal of Global Antimicrobial Resistance. - : Elsevier. - 2213-7165 .- 2213-7173. ; 28, s. 38-42
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The global increase in carbapenem-resistant Enterobacteriaceae (CRE) is a growing health concern. Infections caused by CRE are associated with increased mortality and length of hospital stay, emphasising the health and economic burden posed by these pathogens. Although CRE can inhabit the human gut asymptomatically, colonisation with CRE is associated with an increased risk of CRE infection and mortality. In this study, we investigated the occurrence and characteristics of CRE in faecal samples from healthy persons in 12 villages in Shandong Province, China.METHODS: Screening for CRE in faecal samples was performed by selective cultivation. Minimum inhibitory concentrations (MICs) of meropenem were determined by the agar dilution method. Multilocus sequence typing (MLST) and carbapenemase gene carriage of the isolates were determined by whole-genome sequencing. Genetic relatedness of Escherichia coli isolates was determined by core genome MLST.RESULTS: CRE carriage increased from 2.4% in 2015 to 13.4% in 2017. Most CRE isolates (93.0%) were E. coli and all carried NDM-type carbapenemases. Sequence types (STs) among the E. coli isolates were diverse. The single most common ST was the highly epidemic strain ST167, which was only observed in 2017.CONCLUSION: We report a rapid increase in occurrence of CRE (from 2.4% to 13.4%) among faecal samples collected from healthy rural residents of Shandong Province from 2015 to 2017. Colonisation with CRE is known to increase the risk of CRE infection, and the worrying deterioration of the epidemiological situation in the region reported here indicates a need for further monitoring and possible interventions.
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7.
  • Fei, Yiqiu, et al. (author)
  • The Role of Dihydroresveratrol in Enhancing the Synergistic Effect of Ligilactobacillus salivarius Li01 and Resveratrol in Ameliorating Colitis in Mice
  • 2022
  • In: Research. - : American Association for the Advancement of Science (AAAS). - 2096-5168 .- 2639-5274. ; 2022
  • Journal article (peer-reviewed)abstract
    • Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (10(9) CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1 beta and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT7R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted.
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8.
  • Gu, Congcong, et al. (author)
  • Clonal and plasmid-mediated dissemination of environmental carbapenem-resistant Enterobacteriaceae in large animal breeding areas in northern China
  • 2022
  • In: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 297
  • Journal article (peer-reviewed)abstract
    • The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) constitute a major global health problem. The environment plays an important role in the dissemination of CRE, but large-scale studies on CRE in groundwater environments in animal breeding areas are scarce. The aim of this study was to investigate CRE occurrence and environmental transmission of carbapenem resistance genes in large animal breeding areas in northern China. In total, 280 well water and 102 animal feces samples in large animal breeding areas in six counties from the two provinces Inner Mongolia and Shandong in China, were screened for CRE. A total of 39 CRE were isolated and characterized with next-generation sequencing. 5.3% of well water samples were contaminated with CRE. The well water in chicken farms had the highest number of detections of CRE (15.9%). More than half of the isolates carried closely related, conjugative IncX3 plasmids with blaNDM-genes from multiple geographic areas, indicating that this kind of plasmid plays an important role in dissemination of carbapenem resistance determinants. The clonal expansion of various CRE isolates in well water and animal feces were demonstrated; clonally related CRE were isolated from different wells within the same county, from different counties in the same province, and even from different provinces. In addition to harboring various ARGs, two closely related K. pneumoniae belonging to ST11 isolated from well water carried genetic hypervirulence determinants on a virulence plasmid, highlighting the potential health risk posed by further dissemination of this strain. These findings suggest that groundwater may be an underappreciated reservoir and source of dissemination of CRE, from which resistance genes may disseminate among different bacterial strains and over large geographic distances. Further research and multi-sectorial monitoring, with a "One health" perspective, is urgently needed to investigate the need for interventions aimed at preventing CRE dissemination.
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9.
  • Holmbom, Martin, et al. (author)
  • Risk factors and outcome due to extended-spectrum beta-lactamase-producing uropathogenic Escherichia coli in community-onset bloodstream infections: A ten-year cohort study in Sweden
  • 2022
  • In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 17:11
  • Journal article (peer-reviewed)abstract
    • Objective To study clinical outcome and risk factors associated with extended-spectrum beta-lactamase (ESBL)-producing uropathogenic Escherichia coli (UPEC) in community-onset bloodstream infections (CO-BSI). Methods This was a population-based cohort study including patients with pheno- and genotype-matched ESBL-producing E. coli and non-ESBL- E. coli in urine and blood samples collected in 2009-2018 in southeast Sweden. Seventy-seven episodes of ESBL-UPEC satisfying the inclusion criteria were matched 1:1 with 77 non-ESBL-UPEC for age, gender, and year of culture. Results The most common ST-type and ESBL gene was ST131 (55%), and bla(CTX-M-15) (47%), respectively. Risk factors for ESBL-UPEC were: previous genitourinary invasive procedure (RR 4.66; p = 0.005) or history of ESBL-producing E. coli (RR 12.14; p = 0.024). There was significant difference between ESBL-UPEC and non-ESBL-UPEC regarding time to microbiologically appropriate antibiotic therapy (27:15 h vs. 02:14 h; p = <0.001) and hospital days (9 vs. 5; p = <0.001), but no difference in 30-day mortality (3% vs. 3%; p = >0.999) or sepsis within 36 hours (51% vs. 62%; p = 0.623) was observed. Conclusion The predominant risk factors for ESBL-UPEC were history of ESBL-Ec infection and history of genitourinary invasive procedure. The overall mortality was low and the delay in appropriate antibiotic therapy did not increase the risk for 30-day mortality or risk for sepsis within 36 hours among patients infected with ESBL UPEC. However, these results must be regarded with some degree of caution due to the small sample size.
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10.
  • Kesarimangalam, Sriram, 1983, et al. (author)
  • High diversity of bla NDM-1 -encoding plasmids in Klebsiella pneumoniae isolated from neonates in a Vietnamese hospital
  • 2022
  • In: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 59:2
  • Journal article (peer-reviewed)abstract
    • Objectives: The carbapenemase-encoding gene blaNDM-1 has been reported in Vietnam during the last 10 years, and blaNDM-producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of blaNDM-1 is plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. The diversity of blaNDM-1-encoding plasmids from neonates at a large Vietnamese hospital was characterized in this study. Methods: 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied using optical DNA mapping (ODM) and next-generation sequencing (NGS). Plasmids carrying the blaNDM-1 gene were identified by combining ODM with Cas9 restriction. The plasmids in the isolates were compared to investigate whether the same plasmid was present in different patients. Results: Although the same plasmid was found in some isolates, ODM confirmed that there were at least 10 different plasmids encoding blaNDM-1 among the 18 isolates, thus indicating wide plasmid diversity. The ODM results concur with the NGS data. Interestingly, some isolates had two distinct plasmids encoding blaNDM-1 that could be readily identified with ODM. The coexistence of different plasmids carrying the same blaNDM-1 gene in a single isolate has rarely been reported, probably because of limitations in plasmid characterization techniques. Conclusions: The plasmids encoding the blaNDM-1 gene in this study cohort were diverse and may represent a similar picture in Vietnamese society. The study highlights important aspects of the usefulness of ODM for plasmid analysis.
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