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Shanghai Neisseria gonorrhoeae Isolates Exhibit Resistance to Extended-Spectrum Cephalosporins and Clonal Distribution.

ABSTRACT: The emergence of Neisseria gonorrhoeae strains with resistance (R) to extended-spectrum cephalosporins (ESCsR) represents a public health threat of untreatable gonococcal infections. This study was designed to determine the prevalence and molecular mechanisms of ESCR of Shanghai N. gonorrhoeae isolates. A total of 366 N. gonorrhoeae isolates were collected in 2017 in Shanghai. Susceptibility to ceftriaxone (CRO), cefixime (CFM), azithromycin (AZM), ciprofloxacin (CIP), spectinomycin, penicillin, and tetracycline was determined using the agar dilution method. A subset of 124 isolates was subjected to phylogenetic analysis for nine antimicrobial resistance-associated genes, i.e., penA, porB, ponA, mtrR, 23S rRNA, gyrA, parC, 16S rRNA, and rpsE. Approximately 20.0% of the isolates exhibited CFMR [minimum inhibitory concentration (MIC) >0.125 mg/L], and 5.5% were CROR (MIC > 0.125 mg/L). In total, 72.7% of ESCR isolates were clonal and associated with mosaic penA 10 and 60 alleles. Non-mosaic penA 18 allele and substitutions of PenA A501T, G542S, and PorB1b G213S/Y were observed in non-clonal ESCR. Approximately 6.8% of the isolates showed AZM MIC above the epidemiological cutoff (ECOFF, 1 mg/L), were associated with 23S rRNA A2059G mutation, and did not exhibit clonal distribution. Almost all isolates were CIPR (resistance to ciprofloxacin) and associated with GyrA-91/92 and ParC-85/86/87/88/89/91 alterations. Isolates with ParC S88P substitution were clustered into the ESCR clade. The Shanghai isolates exhibited a high level of ESCR and distinct resistant patterns.

SUBMITTER: Dong Y

PROVIDER: S-EPMC7573285 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Shanghai Neisseria gonorrhoeae Isolates Exhibit Resistance to Extended-Spectrum Cephalosporins and Clonal Distribution.

Dong Yuan Y Yang Yang Y Wang Ying Y Martin Irene I Demczuk Walter W Gu Weiming W

Frontiers in microbiology 20201006

The emergence of Neisseria gonorrhoeae strains with resistance (R) to extended-spectrum cephalosporins (ESCsR) represents a public health threat of untreatable gonococcal infections. This study was designed to determine the prevalence and molecular mechanisms of ESCR of Shanghai N. gonorrhoeae isolates. A total of 366 N. gonorrhoeae isolates were collected in 2017 in Shanghai. Susceptibility to ceftriaxone (CRO), cefixime (CFM), azithromycin (AZM), cipr ...[more]

PMID: 33123111

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Project description:BACKGROUND: The spread of Neisseria gonorrhoeae strains with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins is a major public health problem. While much work has been performed internationally, little is known about the genetics or molecular epidemiology of N. gonorrhoeae isolates with reduced susceptibility to extended-spectrum cephalosporins in the United States. The majority of N. gonorrhoeae infections are diagnosed without a live culture. Molecular tools capable of detecting markers of extended-spectrum cephalosporin resistance are needed. METHODS: Urethral N. gonorrhoeae isolates were collected from 684 men at public health clinics in California in 2011. Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime and azithromycin were determined by Etest and categorized according to the U.S. Centers for Disease Control 2010 alert value breakpoints. 684 isolates were screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive isolates were subjected to DNA sequencing of their penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity of the screening RTPCR in detecting isolates with alert value extended-spectrum cephalosporin MICs, the primers were modified to selectively amplify the mosaic XXXIV penA allele. RESULTS: Three mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study. CONCLUSION: N. gonorrhoeae isolates with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins are currently circulating in California. Isolates with the same NG-MAST ST, penA allele and extended-spectrum cephalosporin MICs have caused treatment failures elsewhere. The RTPCR assay presented here may be useful for the detection of N. gonorrheoae isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs in settings where antimicrobial susceptibility testing is unavailable. In an era of increasing antimicrobial resistance and decreasing culture capacity, molecular assays capable of detecting extended-spectrum cephalosporin of resistance are essential to public health.

Project description:The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient.

Project description:BACKGROUND:Gonorrhea is a major sexually transmitted disease (STD) in many countries worldwide. The emergence of fluoroquinolone resistance has complicated efforts to control and treat this disease. We report the first study of the evolutionary processes acting on transmission dynamics of a resistant gonococcal population from Shanghai, China. We compare these findings with our previous study of the evolution of a fluoroquinolone sensitive gonococcal population from Baltimore, MD. METHODS:Ninety six gonococcal samples were collected from male patients in Shanghai, China. All samples were fluoroquinolone resistant. Seven MLST housekeeping genes, two fluoroquinolone resistance genes (gyrA and parC) and the porB gene were sequenced and subjected to population genetic and evolutionary analyses. We estimated genetic diversity, recombination, growth, and selective pressure. The evolutionary history and population dynamics of the Shanghai population were also inferred and compared with that observed in a fluoroquinolone sensitive gonococcal population from Baltimore. RESULTS:For both populations, mutation plays a larger role than recombination in the evolution of the porB gene, whereas the latter seems to be the main force driving the evolution of housekeeping and fluoroquinolone resistance genes. In both populations there was evidence for positively selected sites in all genes analyzed. The phylogenetic analyses showed no temporal clustering in the Shanghai gonococcal population, nor did we detect shared allelic profiles between the Shanghai and the Baltimore populations. Past population dynamics of gonococcal strains from Shanghai showed a rising relative effective population size (Ne) in MLST genes with a declining relative Ne for gyrA and parC, whereas among sensitive strains from Baltimore we previously observed concordance among these genes. In both Shanghai and Baltimore, the past population dynamics of gonococcal strains tracked changes in the prevalence of gonorrhea. CONCLUSIONS:Our study illustrates both similarities and differences in the evolutionary processes acting on gonococcal populations in different geographic areas. An explanation of this pattern that may apply in China is the continued use of quinolone antibiotics despite widespread resistance. Population genetic analysis of gonococcal strains in conjunction with epidemiological surveillance may provide insights into the epidemic behavior of antibiotic resistant strains and help to design control measures.

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Shanghai Neisseria gonorrhoeae Isolates Exhibit Resistance to Extended-Spectrum Cephalosporins and Clonal Distribution.

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Shanghai <i>Neisseria gonorrhoeae</i> Isolates Exhibit Resistance to Extended-Spectrum Cephalosporins and Clonal Distribution.

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