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  • 1
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    Antibiotic Resistance Patterns and Molecular Characterization of Streptococcus suis Isolates from Swine and Humans in China
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum Vol. 11, No. 3 ( 2023-06-15)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 3 ( 2023-06-15)
    Abstract: Streptococcus suis is a zoonotic pathogen that causes disease in humans after exposure to infected pigs or pig-derived food products. In this study, we examined the serotype distribution, antimicrobial resistance phenotypes and genotypes, integrative and conjugative elements (ICEs), and associated genomic environments of S. suis isolates from humans and pigs in China from 2008 to 2019. We identified isolates of 13 serotypes, predominated by serotype 2 (40/96; 41.7%), serotype 3 (10/96; 10.4%), and serotype 1 (6/96; 6.3%). Whole-genome sequencing analysis revealed that these isolates possessed 36 different sequence types (STs), and ST242 and ST117 were the most prevalent. Phylogenetic analysis revealed possible animal and human clonal transmission, while antimicrobial susceptibility testing indicated high-level resistance to macrolides, tetracyclines, and aminoglycosides. These isolates carried 24 antibiotic resistance genes (ARGs) that conferred resistance to 7 antibiotic classes. The antibiotic resistance genotypes were directly correlated with the observed phenotypes. We also identified ICEs in 10 isolates, which were present in 4 different genetic environments and possessed differing ARG combinations. We also predicted and confirmed by PCR analysis the existence of a translocatable unit (TU) in which the oxazolidinone resistance gene optrA was flanked by IS 1216E elements. One-half (5/10) of the ICE-carrying strains could be mobilized by conjugation. A comparison of the parental recipient with an ICE-carrying transconjugant in a mouse in vivo thigh infection model indicated that the ICE strain could not be eliminated with tetracycline treatment. S. suis therefore poses a significant challenge to global public health and requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation. IMPORTANCE S. suis is a serious zoonotic pathogen. In this study, we investigated the epidemiological and molecular characteristics of 96 S. suis isolates from 10 different provinces of China from 2008 to 2019. A subset of these isolates (10) carried ICEs that were able to be horizontally transferred among isolates of different S. suis serotypes. A mouse thigh infection model revealed that ICE-facilitated ARG transfer promoted resistance development. S. suis requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.00309-23
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
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  • 2
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    Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species
    Springer Science and Business Media LLC ; 2020
    In:  Genome Medicine Vol. 12, No. 1 ( 2020-12)
    Details
    In: Genome Medicine, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2020-12)
    Abstract: The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet (X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants. Methods Herein, we conducted a multiregional whole-genome sequencing study of tet (X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet (X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet (X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses. Results We identified 193 tet (X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet (X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet (X3) ( n  = 188) and tet (X4) ( n  = 5), two tet (X5) variants, tet (X5.2) ( n  = 36) and tet (X5.3) ( n  = 4), were also found together with tet (X3) or tet (X4) but without additive effects on tetracyclines. These tet (X)-positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2–8 μg/mL) and omadacycline (8–16 μg/mL). Genetic analysis revealed that different tet (X) variants shared an analogous IS CR2 -mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet (X)-like genes through horizontal transfer. Conclusions Four tet (X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of IS CR2 in mobilizing tet (X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.
    Type of Medium: Online Resource
    ISSN: 1756-994X
    URL: Article
    DOI: 10.1186/s13073-020-00807-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 3
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    Data_Sheet_9.XLSX
    Frontiers Media SA ; 2022
    In:  Frontiers in Veterinary Science Vol. 9 ( 2022-2-2)
    Details
    In: Frontiers in Veterinary Science, Frontiers Media SA, Vol. 9 ( 2022-2-2)
    Abstract: Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against P. multocida and H. parasuis in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.5 mg/kg. Danofloxacin was well absorbed and fully bioavailable (95.2%) after intramuscular administration of 2.5 mg/kg. The epidemiological cutoff (ECOFF) values of danofloxacin from 931 P. multocida isolates and 263 H. parasuis isolates were 0.03 and 4 mg/L, respectively. Danofloxacin MICs determined in porcine serum were markedly lower than those measured in artificial broth, with a broth/serum ratio of 4.33 for H. parasuis . Compared to P. multocida , danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against H. parasuis . The mean area under the concentration-time curve/MIC (AUC 24h /MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for P. multocida , whereas they were 14.6 and 37.8, respectively, for H. parasuis . Danofloxacin AUC 24h /MIC targets for the same endpoints for P. multocida were higher than those for H. parasuis . At the current dose of 2.5 mg/kg, the PK/PD cutoff (CO PD ) values of danofloxacin against P. multocida and H. parasuis were calculated to be 0.125 and 0.5 mg/L, respectively, based on Monte Carlo simulations. The predicted optimum doses of danofloxacin for a probability of target attainment (PTA) of & gt; 90% to cover the overall MIC population distributions of P. multocida and H. parasuis in this study were 2.38 and 13.36 mg/kg, respectively. These PK/PD-based results have potential relevance for the clinical dose optimization and evaluation of susceptibility breakpoints for danofloxacin in the treatment of swine respiratory tract infections involving these pathogens.
    Type of Medium: Online Resource
    ISSN: 2297-1769
    URL: Article
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    DOI: 10.3389/fvets.2022.811967
    DOI: 10.3389/fvets.2022.811967.s001
    DOI: 10.3389/fvets.2022.811967.s002
    DOI: 10.3389/fvets.2022.811967.s003
    DOI: 10.3389/fvets.2022.811967.s004
    DOI: 10.3389/fvets.2022.811967.s005
    DOI: 10.3389/fvets.2022.811967.s006
    DOI: 10.3389/fvets.2022.811967.s007
    DOI: 10.3389/fvets.2022.811967.s008
    DOI: 10.3389/fvets.2022.811967.s009
    DOI: 10.3389/fvets.2022.811967.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 4
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    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-7-5)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-7-5)
    Abstract: This study aimed to determine the prevalence and transmission characteristics of New Delhi metallo β-lactamase (NDM)-producing Escherichia coli from ducks in Guangdong, China. In this study, a total of 28 NDM-producing E. coli isolates were recovered from 88 unduplicated diseased duck samples (31.8%) from veterinary clinics in Guangzhou, Foshan, Qingyuan, and Huizhou. Two variants, bla NDM−1 and bla NDM−5 , were detected and the latter was present in 89.6% of the isolates (25/28). Multilocus sequence typing (MLST) analysis indicated that these E. coli isolates possessed six distinct STs, and ST156 was the most prevalent followed by ST648, ST746, ST354, ST10, and ST162. In addition, phylogenomic analysis found that two of the isolates that were recovered from a single sample possessed different genomes, and the bla NDM -carrying IncX3 plasmids may be horizontal transfer between E. coli isolates in the intestinal tracts of ducks. Whole-genome sequencing (WGS) analysis further revealed that bla NDM co-existed with other 25 types of antimicrobial resistance genes (ARGs), of which 16 ARGs were highly prevalent with detection rates & gt;50%, and a high incidence of coproducing bla NDM and mcr-1 E. coli isolates (22/88, 25.0%) was detected in ducks. This study underscores the importance of surveillance for bla NDM -harboring microbes in ducks.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2021.677633
    DOI: 10.3389/fmicb.2021.677633.s001
    DOI: 10.3389/fmicb.2021.677633.s002
    DOI: 10.3389/fmicb.2021.677633.s003
    DOI: 10.3389/fmicb.2021.677633.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 5
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    Comparison of the prevalence and molecular characteristics of fosA3 and fosA7 among Salmonella isolates from food animals in China
    Oxford University Press (OUP) ; 2022
    In:  Journal of Antimicrobial Chemotherapy Vol. 77, No. 5 ( 2022-04-27), p. 1286-1295
    Details
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 77, No. 5 ( 2022-04-27), p. 1286-1295
    Abstract: To investigate the prevalence and molecular characteristics of fosA3 and fosA7 among Salmonella isolates. Methods Five hundred and fifty-one Salmonella isolates collected from food animals in China during 2016–19 were screened for fos genes. The drug resistance, serovars, clonal relationships and genetic environments of fosA were compared between fosA7- and fosA3-positive Salmonella. Results A relatively high prevalence of fosA7 (9.26%) and fosA3 (6.53%) was identified. fosA3 was associated with high-level fosfomycin resistance (≥512 mg/L), while fosA7 conferred relatively low-level resistance that was independent of the presence of glucose-6-phosphate. Additionally, fosA7 could facilitate Salmonella survival under oxidative stress. Both fosA3 and fosA7 were found in diverse serovars and STs, but segregated into distinct groups. The fosA3-positive Salmonella Typhimurium/Salmonella Indiana strains showed close genetic relationships, while fosA7-positive Salmonella Meleagridis/Salmonella Agona/Salmonella Derby showed a relatively high degree of whole-genome sequence heterogeneity. fosA3 was located on conjugative IncHI2 plasmids or chromosomes, while fosA7 was strictly chromosomal. Furthermore, two strains carried large chromosomal fosA7 regions within genomic islands. The fosA3 and fosA7 contigs from our isolates and the NCBI could be segregated into four primary and distinct genomic backbones. IS26 and the antibiotic resistance genes (ARGs) blaCTX-M, blaTEM-1B and rmtB were frequently adjacent to fosA3, while fosA7-carrying contigs generally lacked mobile elements and ARGs. Conclusions fosA3 and fosA7 were the primary factors contributing to reduced fosfomycin susceptibility, to different degrees, in these Salmonella isolates. The distinct distributions and molecular characteristics of fosA7 and fosA3 indicated that their origin and evolution in Salmonella were most likely distinct.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    URL: Article
    DOI: 10.1093/jac/dkac061
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-2-5)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-2-5)
    Abstract: We examined the prevalence and transmission of the fosA3 gene among Citrobacter freundii isolates from flowers and the retail environments. We identified 11 fosfomycin-resistant C. freundii strains ( & gt;256 μg/mL) from 270 samples that included petals ( n = 7), leaves ( n = 2), dust ( n = 1) and water ( n = 1). These 11 isolates were multidrug-resistant and most were simultaneously resistant to fosfomycin, cefotaxime, ciprofloxacin and amikacin. Consistently, all 11 isolates also possessed bla CTX–M– 14 , bla CMY– 65 / 122 , aac(6’)-Ib-cr , qnrS1 , qnrB13/6/38 and rmtB . These fosA3 -positive isolates were assigned to two distinct PFGE patterns and one ( n = 9) predominated indicating clonal expansion of fosA3 -positive isolates across flower markets and shops. Correspondingly, fosA3 was co-transferred with bla CTX–M– 14 via two plasmid types by conjugation possessing sizes of 110 kb ( n = 9) and 260 kb ( n = 2). Two representatives were fully sequenced and p12-1 and pS39-1 possessed one and two unclassified replicons, respectively. These plasmids shared a distinctive and conserved backbone in common with fosA3 -carrying C. freundii and other Enterobacteriaceae from human and food animals. However, the fosA3 - bla CTX–M– 14 -containing multidrug resistance regions on these untypable plasmids were highly heterogeneous. To the best of our knowledge, this is the first report of fosA3 and bla CTX–M– 14 that were present in bacterial contaminants from flower shops and markets. These findings underscore a public health threat posed by untypable and transferable p12-1-like and pS39-1-like plasmids bearing fosA3 - bla CTX–M– 14 that could circulate among Enterobacteriaceae species and in particular C. freundi in environmental isolates.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2021.586504
    DOI: 10.3389/fmicb.2021.586504.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 7
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    Occurrence and Transmission of bla NDM -Carrying Enterobacteriaceae from Geese and the Surrounding Environment on a Commercial Goose Farm
    American Society for Microbiology ; 2021
    In:  Applied and Environmental Microbiology Vol. 87, No. 10 ( 2021-04-27)
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 87, No. 10 ( 2021-04-27)
    Abstract: We investigated the prevalence and transmission of NDM-producing Enterobacteriaceae in fecal samples of geese and environmental samples from a goose farm in southern China. The samples were cultivated on MacConkey agar plates supplemented with meropenem. Individual colonies were examined for bla NDM , and bla NDM -positive bacteria were characterized based on whole-genome sequencing (WGS) data from the Illumina and Oxford Nanopore Technologies (ONT) platforms. Of 117 samples analyzed, the carriage rates for New Delhi metallo-β-lactamase (NDM)-positive Enterobacteriaceae were 47.1, 18, and 50% in geese, inanimate environments (sewage, soil, fodder, and dust), and mouse samples, respectively. Two variants ( bla NDM-1 and bla NDM-5 , in 4 and 40 isolates, respectively) were found among 44 bla NDM -positive Enterobacteriaceae ; these variants belonged to eight species, and Escherichia coli was the most prevalent (50%). WGS analysis revealed that bla NDM coexisted with diverse antibiotic resistance genes (ARGs). Population structure analysis showed that most E. coli and Enterobacter sp. isolates were highly heterogeneous, while most Citrobacter sp. and P. stuartii isolates possessed extremely high genetic similarities. In addition, bla NDM-5 -positive ST4358/ST48 E. coli isolates were found to be clonally spread between geese and the environment and were highly genetically similar to those reported from ducks, farm environments, and humans in China. Plasmid analysis indicated that IncX3 pHNYX644-1-like ( n  = 40) and untypeable pM2-1-like plasmids ( n  = 4) mediated bla NDM spread. pM2-1-like plasmids possessed diverse ARGs, including bla NDM-1 , the arsenical and mercury resistance operons, and the maltose operon. Our findings revealed that the goose farm is a reservoir for NDM-positive Enterobacteriaceae . The bla NDM contamination of wild mice and the novel pM2-1-like plasmid described here likely adds to the risk for dissemination of bla NDM and associated resistance genes. IMPORTANCE Carbapenem-resistant bacteria, in particular NDM-producing Enterobacteriaceae , have become a great threat to global public. These bacteria have been found not only in hospital and community environments but also among food animal production chains, which are recognized as reservoirs for NDM-producing Enterobacteriaceae . However, the dissemination of NDM-producing bacteria in waterfowl farms has been less well explored. Our study demonstrates that the horizontal spread of bla NDM -carrying plasmids and the partial clonal spread of bla NDM -positive Enterobacteriaceae contribute to the widespread contamination of bla NDM in the goose farm ecosystem, including mice. Furthermore, we found a novel and transferable bla NDM-1 -carrying multidrug resistance (MDR) plasmid that possessed multiple environmental adaptation-related genes. The outcomes of this study contribute to a better understanding of the prevalence and transmission of bla NDM -carrying Enterobacteriaceae among diverse niches in the farm ecosystem.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/AEM.00087-21
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
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  • 8
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    Pharmacodynamic Target Assessment and PK/PD Cutoff Determination for Gamithromycin Against Streptococcus suis in Piglets
    Frontiers Media SA ; 2022
    In:  Frontiers in Veterinary Science Vol. 9 ( 2022-7-11)
    Details
    In: Frontiers in Veterinary Science, Frontiers Media SA, Vol. 9 ( 2022-7-11)
    Abstract: Gamithromycin is a long-acting azalide antibiotic that has been developed recently for the treatment of swine respiratory diseases. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff, and optimum dosing regimen of gamithromycin were evaluated in piglets against Streptococcus suis in China, including a subset with capsular serotype 2. Short post-antibiotic effects (PAEs) (0.5–2.6 h) and PA-SMEs (2.4–7.7 h) were observed for gamithromycin against S. suis . The serum matrix dramatically facilitated the intracellular uptake of gamithromycin by S. suis strains, thus contributing to the potentiation effect of serum on their susceptibilities, with a Mueller-Hinton broth (MHB)/serum minimum inhibitory concentration (MIC) ratio of 28.86 for S. suis . Dose-response relationship demonstrated the area under the concentration (AUC)/MIC ratio to be the predictive PK/PD index closely linked to activity ( R 2 & gt; 0.93). For S. suis infections, the net stasis, 1–log 10 , and 2–log 10 kill effects were achieved at serum AUC 24h /MIC targets of 17.9, 49.1, and 166 h, respectively. At the current clinical dose of 6.0 mg/kg, gamithromycin PK/PD cutoff value was determined to be 8 mg/L. A PK/PD-based dose assessment demonstrated that the optimum dose regimen of gamithromycin to achieve effective treatments for the observed wild-type MIC distribution of S. suis in China with a probability of target attainment (PTA) ≥ 90% was 2.53 mg/kg in this study. These results will aid in the development of clinical dose-optimization studies and the establishment of clinical breakpoints for gamithromycin in the treatment of swine respiratory infections due to S. suis .
    Type of Medium: Online Resource
    ISSN: 2297-1769
    URL: Article
    DOI: 10.3389/fvets.2022.945632
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 9
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-8-23)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-8-23)
    Abstract: Carbapenems, colistin, and tigecycline are critically important antibiotics in clinics. After the global appearance of bla NDM and mcr mediating the resistance to carbapenems and colistin, respectively, tigecycline becomes the last-resort drug against severe human infections caused by multidrug-resistant bacteria. Recently, a mobile tigecycline resistance gene tet (X4) has been identified in Escherichia coli , Klebsiella pneumoniae , and Acinetobacter baumannii that causes high resistance to tigecycline and other tetracyclines. In this study, the prevalence of tet (X4) in E. coli isolates from duck and goose farms in Southeast China was identified and characterized. Methods Feces, soil, sewage, and dust samples were collected from duck and goose farms along with the southeast coast provinces of China. Antimicrobial susceptibility testing and polymerase chain reaction screening were performed to investigate the phenotype and genotype of tigecycline resistance. Conjugation, S1 pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing were used to determine the transferability, genetic location, and the genomic characteristics of tet (X4). Results In total, 1,716 samples were collected, and 16 isolates (0.9%) recovered from Guangdong, Shandong, and Jiangsu were positive for tet (X4) gene with tigecycline minimum inhibitory concentrations ≥16 mg/L. Notably, among these tet (X4)-positive E. coil isolates, seven of them were from the environment samples (soil and sewage). PFGE and multilocus sequence typing demonstrated that ST3997 was the most prevalent sequence type (eight isolates, 50%) in Jiangsu province. By conjugation assays, 11 isolates were able to transfer tet (X4) plasmid to E. coli C600 recipient, and these plasmids belonged to IncHI1 and IncX1 detected by sequence analysis. tet (X4) was found adjacent to an insertion sequence IS CR2 downstream and a cat D gene upstream for all isolates. In addition, multiple-drug resistance to tigecycline, chlortetracycline, ampicillin, florfenicol, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and fosfomycin was profiled in most of the tet (X4)-positive isolates. Conclusion The identification of tet (X4) harboring E. coli strains in duck farms and their surrounding environment enlarges our knowledge of the variety and prevalence of tigecycline resistance. The prevalence of tet (X4) raises concern for the use of tetracyclines in animal farming, and the tet (X4) gene should be listed as primary gene for resistance surveillance.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2021.716393
    DOI: 10.3389/fmicb.2021.716393.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2019
    In:  Frontiers in Microbiology Vol. 10 ( 2019-1-22)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 10 ( 2019-1-22)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2019.00015
    DOI: 10.3389/fmicb.2019.00015.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
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