Characterization of a novel  -lactamase-producing plasmid in Neisseria gonorrhoeae: sequence analysis and molecular typing of host gonococci

Müller, Etienne; Fayemiwo, Samuel A.; Lewis, David A.

doi:10.1093/jac/dkr162

Cited by 33 publications

(28 citation statements)

References 8 publications

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“…Asia-and Toronto/Rio-type ␤-lactamase plasmids were found in only eight and nine isolates, respectively. Recently, a new type of the ␤-lactamase plasmid (Johannesburg plasmid) was reported by Muller et al (8). If the Johannesburg-type plasmid had existed in our isolates, it would have generated a 450-bp amplicon with the BL1 and BL3 primers in our multiplex PCR system.…”

Section: Resultsmentioning

confidence: 85%

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

Nakayama

Tribuddharat

Prombhul

et al. 2012

Antimicrob Agents Chemother

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Neisseria gonorrhoeae is 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, 96 N. gonorrhoeae isolates with highlevel resistance to penicillin from 121 clinical isolates in Thailand were examined to investigate changes related to their plasmidmediated penicillin resistance and their molecular epidemiological relationships. A ␤-lactamase (TEM) gene variant, bla , that may be a precursor in the transitional stage of a traditional bla TEM-1 gene into an extended-spectrum ␤-lactamase (ESBL), possibly causing high resistance to all extended-spectrum cephalosporins in N. gonorrhoeae, was identified. Clonal analysis using multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing (NG-MAST) revealed the existence of a sexual network among patients from Japan and Thailand. Molecular analysis of the bla TEM-135 gene 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 the bla TEM-135 allele in the penicillinaseproducing N. gonorrhoeae population may call for monitoring for the possible emergence of ESBL-producing N. gonorrhoeae in the future. This study identified a bla TEM variant (bla TEM-135 ) that is a possible intermediate precursor for an ESBL, which warrants international awareness. N eisseria gonorrhoeae is the causative agent of gonorrhea, which is the second most prevalent bacterial sexually transmitted infection globally. During recent decades, N. gonorrhoeae has rapidly developed resistance to most classes of antimicrobials used for treatment of gonorrhea (4,6,17,18,20). Penicillinase-producing N. gonorrhoeae (PPNG), with plasmid-mediated high-level resistance to penicillin, was first reported in 1976 (1, 14) and has since been disseminated worldwide (2). The first gonococcal strain with high-level clinical resistance to ceftriaxone, which is the last remaining option for first-line gonorrhea treatment, was recently found in Japan and completely characterized (9, 11). However, the resistance to ceftriaxone was chromosomally mediated, and no extended-spectrum ␤-lactamase (ESBL) has yet been identified in N. gonorrhoeae. If an ESBL did emerge in N. gonorrhoeae and spread internationally, gonorrhea would become an extremely serious public health problem. PPNG strains are rare in Japan, but these strains have remained highly prevalent in several other countries in Asia (19) and worldwide (20). Penicillin is still also used as the first-line drug in, e.g., some Pacific island countries and the northern part of Australia, because of maintained efficacy in the settings and its low cost.Although the ␤-lactamase (TEM) gene of authentic PPNG is the bla TEM-1 allele, a recently isolated PPNG in Thailand possessed the bla TEM-135 allele, which differs from the bla TEM-1 allel...

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Section: Resultsmentioning

confidence: 85%

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

Nakayama

Tribuddharat

Prombhul

et al. 2012

Antimicrob Agents Chemother

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“…ized as either deletion derivatives of the Asian plasmid (Africa, Toronto, Rio, and Johannesburg plasmids) or insertion derivatives of either the Asian (New Zealand plasmid) or African (Nîmes plasmid) plasmid (30,(178)(179)(180)(181)(182). All these plasmids likely contain a TnA (Tn2) transposable element carrying the bla TEM-1 gene that encodes TEM-1 ␤-lactamase.…”

Section: Penicillin Resistancementioning

confidence: 99%

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

2014

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SUMMARY Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae , including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection.

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“…The Asian plasmid has been considered to be the ancestral plasmid from which the other plasmids evolved through deletions and/or insertions. Accordingly, these β-lactamase producing plasmids may be characterised as either deletion derivates of the Asian plasmid (Africa, Rio/Toronto and Johannesburg) or insertion derivatives of either the Asian (New Zealand) or African (Nimes) plasmids [4, 24–27]. …”

Section: Introductionmentioning

confidence: 99%

Characterisation of bla TEM genes and types of β-lactamase plasmids in Neisseria gonorrhoeae – the prevalent and conserved bla TEM-135 has not recently evolved and existed in the Toronto plasmid from the origin

et al. 2014

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BackgroundAntimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern worldwide. It has been recently feared that the blaTEM-1 gene is, via blaTEM-135, evolving into an extended-spectrum β-lactamase (ESBL), which could degrade all cephalosporins including ceftriaxone. The aims of the present study were to characterize the blaTEM genes, types of β-lactamase plasmids, the degradation of ampicillin by TEM-135 compared to TEM-1, and to perform molecular epidemiological typing of β-lactamase-producing N. gonorrhoeae strains internationally.Methodsβ-lactamase producing N. gonorrhoeae isolates (n = 139) cultured from 2000 to 2011 in 15 countries were examined using antibiograms, blaTEM gene sequencing, β-lactamase plasmid typing, and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Furthermore, the blaTEM gene was sequenced in the first described Toronto plasmid (pJD7), one of the first Asian plasmids (pJD4) and African plasmids (pJD5) isolated in Canada. The degradation of ampicillin by TEM-135 compared to TEM-1 was examined using a MALDI-TOF MS hydrolysis assay.ResultsSix different blaTEM sequences were identified (among isolates with 125 different NG-MAST STs), i.e. blaTEM-1 (in 104 isolates), blaTEM-135 (in 30 isolates), and four novel blaTEM sequences (in 5 isolates). The blaTEM-1 allele was only found in the African and Asian plasmids, while all Rio/Toronto plasmids possessed the blaTEM-135 allele. Most interesting, the first described gonococcal Toronto plasmid (pJD7), identified in 1984, also possessed the highly conserved blaTEM-135 allele. The degradation of ampicillin by TEM-135 compared to TEM-1 was indistinguishable in the MALDI-TOF MS hydrolysis assay.ConclusionsblaTEM-135, encoding TEM-135, is predominantly and originally associated with the Rio/Toronto plasmid and prevalent among the β-lactamase producing gonococcal strains circulating globally. blaTEM-135 does not appear, as previously hypothesized, to have recently evolved due to some evolutionary selective pressure, for example, by the extensive use of extended-spectrum cephalosporins worldwide. On the contrary, the present study shows that blaTEM-135 existed in the Toronto plasmid from its discovery and that blaTEM-135 is highly conserved (not further evolved in the past >30 years). Nevertheless, international studies for monitoring the presence of different blaTEM alleles, the possible evolution of the blaTEM-135 allele, and the types of β-lactamase producing plasmids, remain imperative.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-454) contains supplementary material, which is available to authorized users.

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Characterization of a novel -lactamase-producing plasmid in Neisseria gonorrhoeae: sequence analysis and molecular typing of host gonococci

Cited by 33 publications

References 8 publications

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

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

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

Characterisation of bla TEM genes and types of β-lactamase plasmids in Neisseria gonorrhoeae – the prevalent and conserved bla TEM-135 has not recently evolved and existed in the Toronto plasmid from the origin

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