scholarly journals Antimicrobial resistance, genetic resistance determinants for ceftriaxone and molecular epidemiology of Neisseria gonorrhoeae isolates in Nanjing, China

2014 ◽  
Vol 69 (11) ◽  
pp. 2959-2965 ◽  
Author(s):  
Shao-Chun Chen ◽  
Yue-Ping Yin ◽  
Xiu-Qin Dai ◽  
Magnus Unemo ◽  
Xiang-Sheng Chen
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Molecular Epidemiology ◽  
Genetic Resistance ◽  
Resistance Determinants

scholarly journals Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae

2020 ◽  
Author(s):  
Koji Yahara ◽  
Kevin C. Ma ◽  
Tatum D. Mortimer ◽  
Ken Shimuta ◽  
Shu-ichi Nakayama ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Neisseria Gonorrhoeae ◽  
Standard Treatment ◽  
Genetic Resistance ◽  
Antibiotic Use ◽  
First Line ◽  
Resistance Determinants ◽  
Antimicrobial Resistance Genes

AbstractAntimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to treatment with third-generation cephalosporins mainly due to the emergence of mosaic penA alleles. These two STs were first detected in Japan; however, when and how the mosaic penA alleles emerged and spread to other countries remains unknown. Here, we addressed the evolution of penA alleles by obtaining complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic penA allele 34 (penA-34) dating from 2005 and generating a phylogenetic representation of 1,075 strains sampled from 37 countries. We also sequenced the genomes of 103 Japanese ST-7363 N. gonorrhoeae isolates from 1996-2005 and reconstructed a phylogeny including 88 previously sequenced genomes. Based on an estimate of the time of emergence of ST-1901 harboring mosaic penA-34 and ST-7363 harboring mosaic penA-10, and >300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996-2015, we suggest that penA-34 in ST-1901 was generated from penA-10 via recombination with another Neisseria species, followed by a second recombination event with a gonococcal strain harboring wildtype penA-1. Following the acquisition of penA-10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, possibly due to independent mutations rather than horizontal gene transfer. Literature data suggest the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time. Our findings highlight how recombination and antibiotic use across and within Neisseria species intersect in driving the emergence and spread of drug-resistant gonorrhea.Author summaryAntimicrobial resistance is recognized as one of the greatest threats to human health, and Neisseria gonorrhoeae resistance is classified as one of the most urgent. The two major internationally spreading lineages resistant. to first line drugs likely originated in Japan, but when and how their genetic resistance determinants emerged remain unknown. In this study, we conducted an evolutionary analysis using clinical N. gonorrhoeae isolates from 37 countries, including a historical collection of Japanese isolates, to investigate the emergence of resistance in each of the two major lineages. We showed that the penA allele responsible for resistance to cephalosporins, the first-line treatment for gonorrhea, was possibly generated by two recombination events, one from another Neisseria species and one from another N. gonorrhoeae lineage. We also showed that mutations responsible for resistance to a previously widely used antibiotic treatment occurred twice independently in one of the two major lineages. The emergence of the genetic resistance determinants potentially reflects selection from the standard treatment regimen at that time. Our findings highlight how recombination (horizontal gene transfer) and antibiotic use across and within a bacterial species intersect in driving the emergence and spread of antimicrobial resistance genes and mutations.

scholarly journals Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015–16

2020 ◽  
Vol 75 (6) ◽  
pp. 1432-1438 ◽  
Author(s):  
Pham Thi Lan ◽  
Daniel Golparian ◽  
Johan Ringlander ◽  
Le Van Hung ◽  
Nguyen Van Thuong ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Reproductive Health ◽  
Neisseria Gonorrhoeae ◽  
Molecular Epidemiology ◽  
Genomic Analysis ◽  
Illumina Miseq ◽  
Phylogenomic Analysis ◽  
Asian Countries ◽  
Resistant Strains ◽  
A Minor

Abstract Objectives Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015–16 in Vietnam using AMR testing, WGS and detection of AMR determinants. Methods Two hundred and twenty-nine gonococcal isolates cultured in 2015–16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq. Results Resistance among the 2015–16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2–8 mg/L. Among the 2015–16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q. Conclusions From 2011 to 2015–16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.

scholarly journals Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance, a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains

2017 ◽  
Vol 55 (5) ◽  
pp. 1454-1468 ◽  
Author(s):  
W. Demczuk ◽  
S. Sidhu ◽  
M. Unemo ◽  
D. M. Whiley ◽  
V. G. Allen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Dna Sequences ◽  
Diversity Index ◽  
23S Rrna ◽  
Content Type ◽  
Typing Scheme ◽  
Resistance Determinants ◽  
Index Value ◽  
User Friendly

ABSTRACTA curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants inNeisseria gonorrhoeaewas developed and is publicly accessible (https://ngstar.canada.ca). TheN. gonorrhoeaeSequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA,mtrR,porB,ponA,gyrA,parC, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entirepenAsequence, combining the historical nomenclature forpenAtypes I to XXXVIII with novel nucleotide sequence designations; the fullmtrRsequence and a portion of its promoter region; portions ofponA,porB,gyrA, andparC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n= 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n= 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n= 100; 13.0%), ST-42 and ST-91 (n= 45; 5.9%), ST-64 (n= 44; 5.72%), and ST-139 (n= 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n= 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n= 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n= 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n= 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistantN. gonorrhoeaestrains.

scholarly journals Typing of Neisseria gonorrhoeae Isolates in Shenzhen, China, from 2014 to 2018 Reveals the Shift of Genotypes Significantly Associated with Antimicrobial Resistance

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Yizhun Li ◽  
Yamei Li ◽  
Leshan Xiu ◽  
Yaling Zeng ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Molecular Epidemiology ◽  
Important Data ◽  
Content Type ◽  
Future Studies ◽  
Ideal Tool ◽  
Global Threat ◽  
Sequence Types

ABSTRACT The growing antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. Molecular typing is an ideal tool to reveal the association between specific genotypes and resistance phenotypes that provide effective data for tracking the transmission of resistant clones of N. gonorrhoeae. In our study, we aimed to describe the molecular epidemiology of AMR and the distribution of resistance-associated genotypes in Shenzhen, China, during 2014 to 2018. In total, 909 isolates were collected from Shenzhen from 2014 to 2018. Two typing schemes, multilocus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR), were performed for all isolates. The distribution of resistance-associated genotypes was described using goeBURST analysis combined with logistic regression data. Among 909 isolates, sequence type 8123 (ST8123), ST7363, ST1901, ST7365, and ST7360 were the most common MLST sequence types, and ST348, ST2473, ST497, and ST199 were the most prevalent NG-STAR STs. Logistic regression analysis showed that NG-STARST497, MLSTST7365, and MLSTST7360 were typically associated with decreased susceptibility to ceftriaxone. Furthermore, the internationally spreading extended-spectrum cephalosporin (ESC)-resistant clone MLSTST1901 has been prevalent since at least 2014 in Shenzhen and showed a significant increase during 2014 to 2018. Additionally, MLSTST7363 owns the potential to become the next internationally spreading ceftriaxone-resistant ST. In conclusion, we performed a comprehensive epidemiological study to explore the correlation between AMR and specific STs, which provided important data for future studies of the molecular epidemiology of AMR in N. gonorrhoeae. Besides, these findings provide insight for adjusting surveillance strategies and therapy management in Shenzhen.

scholarly journals Equations To Predict Antimicrobial MICs in Neisseria gonorrhoeae Using Molecular Antimicrobial Resistance Determinants

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Walter Demczuk ◽  
Irene Martin ◽  
Pam Sawatzky ◽  
Vanessa Allen ◽  
Brigitte Lefebvre ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Training Data ◽  
Sequencing Analysis ◽  
Regression Equations ◽  
Validation Data ◽  
Data Set ◽  
Content Type ◽  
Resistance Determinants ◽  
Extended Spectrum

ABSTRACT The emergence of Neisseria gonorrhoeae strains that are resistant to azithromycin and extended-spectrum cephalosporins represents a public health threat, that of untreatable gonorrhea infections. Multivariate regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to the overall antimicrobial MICs for ceftriaxone, cefixime, azithromycin, tetracycline, ciprofloxacin, and penicillin. A training data set consisting of 1,280 N. gonorrhoeae strains was used to generate regression equations which were then applied to validation data sets of Canadian (n = 1,095) and international (n = 431) strains. The predicted MICs for extended-spectrum cephalosporins (ceftriaxone and cefixime) were fully explained by 5 amino acid substitutions in PenA, A311V, A501P/T/V, N513Y, A517G, and G543S; the presence of a disrupted mtrR promoter; and the PorB G120 and PonA L421P mutations. The correlation of predicted MICs within one doubling dilution to phenotypically determined MICs of the Canadian validation data set was 95.0% for ceftriaxone, 95.6% for cefixime, 91.4% for azithromycin, 98.2% for tetracycline, 90.4% for ciprofloxacin, and 92.3% for penicillin, with an overall sensitivity of 99.9% and specificity of 97.1%. The correlations of predicted MIC values to the phenotypically determined MICs were similar to those from phenotype MIC-only comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular data will facilitate the transition to whole-genome sequencing analysis from phenotypic testing and can fill the surveillance gap in an era of increased reliance on nucleic acid assay testing (NAAT) diagnostics to better monitor the dynamics of N. gonorrhoeae.

Antimicrobial resistance in Campylobacter coli and Campylobacter jejuni from human campylobacteriosis in Taiwan, 2016–2019

2021 ◽  
Author(s):  
Ying-Shu Liao ◽  
Bo-Han Chen ◽  
Ru-Hsiou Teng ◽  
You-Wun Wang ◽  
Jui-Hsien Chang ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Efflux Pump ◽  
Genetic Resistance ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Campylobacter Coli ◽  
Rapid Diagnostics ◽  
Phenotypic Resistance ◽  
Resistance Determinants ◽  
Level Resistance

Campylobacter coli and C. jejuni are highly resistant to most therapeutic antimicrobials in Taiwan, rapid diagnostics of resistance in bacterial isolates is crucial for the treatment of campylobacteriosis. We characterized 219 (40 C. coli and 179 C. jejuni ) isolates recovered from humans between 2016 and 2019 using whole-genome sequencing to investigate the genetic diversity among isolates and the genetic resistance determinants associated with antimicrobial resistance. Susceptibility testing with 8 antimicrobials was conducted to assess the concordance between phenotypic resistance and genetic determinants. The conventional and core genome multilocus sequence typing analysis revealed diverse clonality among the isolates. Mutations in gyrA (T86I, D90N), rpsL (K43R, K88R), and 23S rRNA (A2075G) were found in 91.8%, 3.2%, and 6.4% of the isolates, respectively. Horizontally transferable resistance genes ant( 6 )-I , aad9 , aph(3’)-IIIa , aph(2”) , blaOXA , catA / fexA , cfr(C) , erm(B) , lnu , sat4 , and tet were identified in 24.2%, 21.5%, 33.3%, 11.9%, 96.3%, 10.0%, 0.9%, 6.8%, 3.2%, 13.2%, and 96.3%, respectively. High-level resistance to 8 antimicrobials in isolates was 100% predictable by the known resistance determinants, whereas low-level resistance to azithromycin, clindamycin, nalidixic acid, ciprofloxacin, and florfenicol in isolates was associated with sequence variations in CmeA and CmeB of the CmeABC efflux pump. Resistance-enhancing CmeB variants were identified in 62.1% (136/219) of isolates. In conclusion, an extremely high proportion of C. coli (100%) and C. jejuni (88.3%) were multidrug-resistant and a high proportion (62.5%) of C. coli isolates had been resistant to azithromycin, erythromycin, and clindamycin that would complicate the treatment of invasive campylobacteriosis in this country.

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