scholarly journals Dissemination and genome analysis of high-level ceftriaxone-resistant penA 60.001 Neisseria gonorrhoeae strains from the Guangdong Gonococcal Antibiotics Susceptibility Programme (GD-GASP), 2016-2019

2022 ◽  
pp. 1-19
Author(s):  
Xiaomian Lin ◽  
Wentao Chen ◽  
Qinghui Xie ◽  
Yuqi Yu ◽  
Yiwen Liao ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Genome Analysis ◽  
Antibiotics Susceptibility ◽  
High Level

scholarly journals Molecular pathways to high-level azithromycin resistance in Neisseria gonorrhoeae

2021 ◽  
Author(s):  
J G E Laumen ◽  
S S Manoharan-Basil ◽  
E Verhoeven ◽  
S Abdellati ◽  
I De Baetselier ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Ribosomal Proteins ◽  
Efflux Pump ◽  
23S Rrna ◽  
Rrna Gene ◽  
23S Rrna Gene ◽  
Evolution Of Resistance ◽  
High Level ◽  
Azithromycin Resistance ◽  
Level Resistance

Abstract Background The prevalence of azithromycin resistance in Neisseria gonorrhoeae is increasing in numerous populations worldwide. Objectives To characterize the genetic pathways leading to high-level azithromycin resistance. Methods A customized morbidostat was used to subject two N. gonorrhoeae reference strains (WHO-F and WHO-X) to dynamically sustained azithromycin pressure. We tracked stepwise evolution of resistance by whole genome sequencing. Results Within 26 days, all cultures evolved high-level azithromycin resistance. Typically, the first step towards resistance was found in transitory mutations in genes rplD, rplV and rpmH (encoding the ribosomal proteins L4, L22 and L34 respectively), followed by mutations in the MtrCDE-encoded efflux pump and the 23S rRNA gene. Low- to high-level resistance was associated with mutations in the ribosomal proteins and MtrCDE efflux pump. However, high-level resistance was consistently associated with mutations in the 23S ribosomal RNA, mainly the well-known A2059G and C2611T mutations, but also at position A2058G. Conclusions This study enabled us to track previously reported mutations and identify novel mutations in ribosomal proteins (L4, L22 and L34) that may play a role in the genesis of azithromycin resistance in N. gonorrhoeae.

scholarly journals Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

2014 ◽  
Vol 53 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Walter Demczuk ◽  
Tarah Lynch ◽  
Irene Martin ◽  
Gary Van Domselaar ◽  
Morag Graham ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Large Scale ◽  
Epidemiological Studies ◽  
23S Rrna ◽  
Genome Comparison ◽  
Whole Genome ◽  
Content Type ◽  
Genomic Epidemiology ◽  
High Level ◽  
Sequence Types

A large-scale, whole-genome comparison of CanadianNeisseria gonorrhoeaeisolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While someN. gonorrhoeaemultiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaicpenAalleles, followed in 2000/2001 with thepenAmosaic X allele and then in 2007 with ST1407 strains with thepenAmosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated withpenAmosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections.

scholarly journals Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae

2002 ◽  
Vol 184 (20) ◽  
pp. 5619-5624 ◽  
Author(s):  
Wendy L. Veal ◽  
Robert A. Nicholas ◽  
William M. Shafer
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Base Pair ◽  
Efflux Pump ◽  
Penicillin Resistance ◽  
Single Base ◽  
Base Pair Deletion ◽  
Resistance To Penicillin ◽  
Single Base Pair ◽  
High Level ◽  
Level Resistance

ABSTRACT The importance of the mtrCDE-encoded efflux pump in conferring chromosomally mediated penicillin resistance on certain strains of Neisseria gonorrhoeae was determined by using genetic derivatives of penicillin-sensitive strain FA19 bearing defined mutations (mtrR, penA, and penB) donated by a clinical isolate (FA6140) expressing high-level resistance to penicillin and antimicrobial hydrophobic agents (HAs). When introduced into strain FA19 by transformation, a single base pair deletion in the mtrR promoter sequence from strain FA6140 was sufficient to provide high-level resistance to HAs (e.g., erythromycin and Triton X-100) but only a twofold increase in resistance to penicillin. When subsequent mutations in penA and porIB were introduced from strain FA6140 into strain WV30 (FA19 mtrR) by transformation, resistance to penicillin increased incrementally up to a MIC of 1.0 μg/ml. Insertional inactivation of the gene (mtrD) encoding the membrane transporter component of the Mtr efflux pump in these transformant strains and in strain FA6140 decreased the MIC of penicillin by 16-fold. Genetic analyses revealed that mtrR mutations, such as the single base pair deletion in its promoter, are needed for phenotypic expression of penicillin and tetracycline resistance afforded by the penB mutation. As penB represents amino acid substitutions within the third loop of the outer membrane PorIB protein that modulate entry of penicillin and tetracycline, the results presented herein suggest that PorIB and the MtrC-MtrD-MtrE efflux pump act synergistically to confer resistance to these antibiotics.

scholarly journals Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales

2008 ◽  
Vol 13 (15) ◽  
Author(s):  
S A Chisholm ◽  
C Ison
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Sequence Type ◽  
Surveillance Programme ◽  
England And Wales ◽  
High Level ◽  
First Time ◽  
Azithromycin Resistance

The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales has monitored azithromycin resistance since 2001. In 2007, high-level azithromycin resistance (MICs >256 mg/L) was identified for the first time in six isolates, all of which were the same sequence type (ST 649).

scholarly journals Molecular Analyses of TEM Genes and Their Corresponding Penicillinase-Producing Neisseria gonorrhoeae Isolates in Bangkok, Thailand

2011 ◽  
Vol 56 (2) ◽  
pp. 916-920 ◽  
Author(s):  
Shu-ichi Nakayama ◽  
Chanwit Tribuddharat ◽  
Sasiprapa Prombhul ◽  
Ken Shimuta ◽  
Somporn Srifuengfung ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Sexual Network ◽  
Genetic Event ◽  
Content Type ◽  
Extended Spectrum ◽  
Resistance To Penicillin ◽  
High Level ◽  
International Awareness

ABSTRACTNeisseria gonorrhoeaeis a major public health problem globally, especially because the bacterium has developed resistance to most antimicrobials introduced for first-line treatment of gonorrhea. In the present study, 96N. gonorrhoeaeisolates with high-level resistance to penicillin from 121 clinical isolates in Thailand were examined to investigate changes related to their plasmid-mediated penicillin resistance and their molecular epidemiological relationships. A β-lactamase (TEM) gene variant,blaTEM-135, that may be a precursor in the transitional stage of a traditionalblaTEM-1gene into an extended-spectrum β-lactamase (ESBL), possibly causing high resistance to all extended-spectrum cephalosporins inN. gonorrhoeae, was identified. Clonal analysis using multilocus sequence typing (MLST) andN. gonorrhoeaemultiantigen sequence typing (NG-MAST) revealed the existence of a sexual network among patients from Japan and Thailand. Molecular analysis of theblaTEM-135gene showed that the emergence of this allele might not be a rare genetic event and that the allele has evolved in different plasmid backgrounds, which results possibly indicate that it is selected due to antimicrobial pressure. The presence of theblaTEM-135allele in the penicillinase-producingN. gonorrhoeaepopulation may call for monitoring for the possible emergence of ESBL-producingN. gonorrhoeaein the future. This study identified ablaTEMvariant (blaTEM-135) that is a possible intermediate precursor for an ESBL, which warrants international awareness.

Emergence and dissemination of three mild outbreaks of Neisseria gonorrhoeae with high-level resistance to azithromycin in Barcelona, 2016–18

2020 ◽  
Author(s):  
P Salmerón ◽  
A Moreno-Mingorance ◽  
J Trejo ◽  
R Amado ◽  
B Viñado ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
23S Rrna ◽  
Phylogenomic Analysis ◽  
Rrna Gene ◽  
Snp Analysis ◽  
Enhanced Resolution ◽  
23S Rrna Gene ◽  
High Level ◽  
Level Resistance

Abstract Background Neisseria gonorrhoeae (NG) isolates with high-level azithromycin resistance (HL-AziR) have emerged worldwide in recent decades, threatening the sustainability of current dual-antimicrobial therapy. Objectives This study aimed to characterize the first 16 NG isolates with HL-AziR in Barcelona between 2016 and 2018. Methods WGS was used to identify the mechanisms of antimicrobial resistance, to establish the MLST ST, NG multiantigen sequence typing (NG-MAST) ST and NG sequence typing for antimicrobial resistance (NG-STAR) ST and to identify the clonal relatedness of the isolates with other closely related NG previously described in other countries based on a whole-genome SNP analysis approach. The sociodemographic characteristics of the patients included in the study were collected by comprehensive review of their medical records. Results Twelve out of 16 HL-AziR isolates belonged to the MLST ST7823/NG-MAST ST5309 genotype and 4 to MLST ST9363/NG-MAST ST3935. All presented the A2059G mutation in all four alleles of the 23S rRNA gene. MLST ST7823/NG-MAST ST5309 isolates were only identified in men who have sex with women and MLST ST9363/NG-MAST ST3935 were found in MSM. Phylogenomic analysis revealed the presence of three transmission clusters of three different NG strains independently associated with sexual behaviour. Conclusions Our findings support the first appearance of three mild outbreaks of NG with HL-AziR in Spain. These results highlight the continuous capacity of NG to develop antimicrobial resistance and spread among sexual networks. The enhanced resolution of WGS provides valuable information for outbreak investigation, complementing the implementation of public health measures focused on the prevention and dissemination of MDR NG.

scholarly journals Survey ofNeisseria gonorrhoeaeAntimicrobial Susceptibility in Ontario

1990 ◽  
Vol 1 (4) ◽  
pp. 136-138
Author(s):  
Vivian G Loo ◽  
Andrew E Simor ◽  
Ruth Jaeger ◽  
Donald E Low
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Tetracycline Resistance ◽  
Beta Lactamase ◽  
Minimal Inhibitory Concentrations ◽  
High Level ◽  
L 13

The minimal inhibitory concentrations (MICs) of penicillin, tetracycline, erythromycin, cefoxitin, ceftriaxone and spectinomycin were determined for 300 consecutive strains ofNeisseria gonorrhoeaecollected from physicians’ offices in Ontario. Only four isolates were found to produce beta-lactamase. Of the remaining 296 isolates, five (1.7%) had penicillin MICs greater than or equal to 1 mg/L, 78 (26.3%) had tetracycline MICs greater than or equal to 1 mg/L, 13 (4.4%) had cefoxitin MICs greater than or equal to 1 mg/L and 43 (14.5%) had erythromycin MICs greater than or equal to 1 mg/L. Two isolates (0.7%) had high level tetracycline resistance with MICs greater than or equal to 16 mg/L. AllN gonorrhoeaeisolates were susceptible to ceftriaxone and to spectinomycin.

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