Insertion of a thymine (+T) in the 13 base pair inverted repeat of the Neisseria gonorrhoeae mtr promoter region and antibiotic susceptibility

Cousin, Sydney L.; Roberts, Marilyn C.; Whittington, William L. H.

doi:10.1016/j.ijantimicag.2004.01.001

Cited by 6 publications

(7 citation statements)

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“…It has been proposed that resistance due to chromosomal mutations is a result of a complicated interplay between reduced affinities of modified penicillin-binding proteins (encoded by the penA and ponA genes) to penicillin, activation of the MtrC-MtrD-MtrE efflux pump (by mutation in the promoter region of the mtrR gene), and reduction in the permeation of the outer membrane porin PorB1b (encoded by porB1b) (i.e., by penB mutations) (4,9,10,19,23). It is likely that mutations in the pilQ gene, encoding a protein of the secretin family, are also involved in the development of resistance to penicillin (32).…”

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confidence: 99%

Relation between Genetic Markers of Drug Resistance and Susceptibility Profile of Clinical Neisseria gonorrhoeae Strains

Ilina

Vereshchagin

Borovskaya

et al. 2008

Antimicrob Agents Chemother

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The main goal of this work is to clarify the predictive value of known genetic markers of Neisseria gonorrhoeae resistance to penicillin, tetracycline, and fluoroquinolones. The correlation between the presence of certain genetic markers and susceptibility of N. gonorrhoeae isolates to penicillin, tetracycline, and fluoroquinolones has been analyzed by means of statistical methods. Susceptibility testing with penicillin, tetracycline, and fluoroquinolones was performed by the agar dilution method. N. gonorrhoeae genomic DNA was isolated. The presence of bla TEM-1 and tet(M) genes was analyzed by PCR. A novel method of polymorphism discovery based on a minisequencing reaction followed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry was applied for the analysis of chromosomal N. gonorrhoeae genes involved in antimicrobial resistance development. Clinical N. gonorrhoeae isolates (n ‫؍‬ 464) were collected. Susceptibility levels to penicillin, tetracycline, and fluoroquinolones were found to be 25.9%, 35.9%, and 54.1%, respectively. Among the 19 N. gonorrhoeae isolates with penicillin MICs of >4 g/ml, the bla TEM-1 gene was detected in 12. The Tet(M) determinant was found in 4 of 12 N. gonorrhoeae isolates with tetracycline MICs of >16 g/ml. The chromosomal genetic markers of penicillin and tetracycline resistance were detected especially in isolates with penicillin MICs of 0.25 to 2.0 g/ml and tetracycline MICs of 0.5 to 4 g/ml. Mutations in GyrA and ParC were found in 208 of 211 quinoloneresistant N. gonorrhoeae isolates. This work is the first representative molecular research of the N. gonorrhoeae population in Russia. Information about the prevalence of antibiotic resistance mechanisms and the positive predictive value of certain genetic determinants is given. The positive predictive values of the analyzed genetic markers were found to be different for fluoroquinolones (90.3%), penicillin (91.1%), and tetracycline (81.9%).

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confidence: 99%

Relation between Genetic Markers of Drug Resistance and Susceptibility Profile of Clinical Neisseria gonorrhoeae Strains

Ilina

Vereshchagin

Borovskaya

et al. 2008

Antimicrob Agents Chemother

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“…Structural mutations include truncations of the mtrR gene (85) or amino acid substitutions within the theoretical DNA binding domain of the MtrR protein (38,69,107,113,118,174,182,184). Two key promoter mutations have also been described; one is the insertion of a Correia element in the MtrR binding site (85,118), and the other an insertion or deletion of one or two thymidines within the pseudo-inverted repeat of the MtrR binding site (34,38,104,130,184,210,211). The +/-T promoter mutations in particular are frequently isolated and known to cause a greater derepression state of the mtrCDE operon than structural mtrR mutants (65,174).…”

Section: Discussionmentioning

confidence: 99%

“…The most common mutation is a single base pair deletion located in the inverted repeat that acts as the shared but divergent promoter regions of mtrR and mtrCDE (34,38,104,130,184,210,211). Other commonly described mutations are located in the structural gene of mtrR, and include a G45D mutation (38,174,184,198,210) and an A39T mutation (38), which are found in the Here we compared five different mtrR mutations that were isolated clinically or from experimentally infected mice to determine if they confer differential levels of mtrCDE operon derepression as measured by levels of RNA transcript, protein production, antibiotic resistance, and in vivo fitness.…”

Section: Introductionmentioning

confidence: 99%

“…Phenotypically, these strains exhibit increased levels of resistance to MtrCMtrD-MtrE efflux pump substrates Triton X-lOO (TX-lOO), erythromycin (Em), and azithromycin (Az) (140). A series of publications that detailed the presence of naturally occurring mtr mutants in clinical isolates suggested a fitness benefit or selective factor present in nature that allows for natural mtr mutants to flourish (34,113,118,126,130,184,198,205,210,211). Consistent with these findings, previous work from this lab showed that the mtr phenotype conveys a fitness increase in the murine model of lower genital tract infection (Warner et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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The Role of the Transcription Factors MtrR and MtrA in the Fitness of the Pathogen Neisseria gonorrhoeae

Warner¹

2007

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“…A single-nucleotide deletion (ϪT) in the inverted repeat, which causes both the loss of transcription of mtrR and increased transcription of mtrCDE, is the most-prevalent mechanism by which clinical isolates overexpress the MtrC-MtrD-MtrE efflux system (5,18,37,41). Within the coding region of mtrR, mutations in the DNA-binding domain have also been shown to be associated with increased expression of the mtrCDE operon (26).…”

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Genotyping as a Tool for Antibiotic Resistance Surveillance of Neisseria gonorrhoeae in New Caledonia: Evidence of a Novel Genotype Associated with Reduced Penicillin Susceptibility

Vernel-Pauillac

Nandi

Nicholas

et al. 2008

Antimicrob Agents Chemother

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Antibiotic resistance in Neisseria gonorrhoeae continues to be a major concern in public health. Resistance of N. gonorrhoeae bacteria to penicillin G is widespread in most developed countries, which has necessitated a change to newer drugs for treatment of gonococcal infections. Recent reports indicate that resistance to these newer drugs is increasing, highlighting the need for accurate therapeutic recommendations. In some countries or communities, however, N. gonorrhoeae isolates are still susceptible to penicillin, so the use of this antibiotic for single-dose treatments of medically under-resourced patients is beneficial. In order to evaluate the adequacy and sustainability of this treatment approach, we explored the presence and prevalence of chromosomally mediated resistance determinants in N. gonorrhoeae isolates collected from 2005 to 2007 in New Caledonia. We developed two new real-time PCR assays targeting the penB and mtrR determinants, to be used together with a previously described duplex assay targeting the penA and ponA determinants. The results of this study provided evidence that neither the most-common mtrR determinants nor the most-resistance-associated penB alleles are currently circulating in New Caledonia, suggesting that penicillin should still be considered a valuable treatment strategy. Additionally, using our genotyping assay, we observed an unexpected penB genotype at a relatively high frequency that was associated with a decreased susceptibility to penicillin (average MIC, 0.15 g/ml). Sequencing revealed that this genotype corresponded to an A102S mutation in the penB gene. The molecular tools developed in this study can be used successfully for prospective epidemiological monitoring and surveillance of penicillin susceptibility.Neisseria gonorrhoeae is an obligate gram-negative human pathogenic bacterium that continues to be a public health problem worldwide (31). It is well documented that N. gonorrhoeae bacteria have evolved resistance mechanisms to almost all antimicrobial compounds that have been used to treat infections, an ability that has largely been related to the capacity for natural recombination between strains of the same species within a human host and with other members of the natural human mucosal flora, notably saprophytic and other pathogenic Neisseria species (7,27,29,30).Antimicrobial resistance mechanisms include the production of antibiotic-degrading enzymes, modification of the target site, and decreased influx or increased efflux of the antibiotic (1, 13). Penicillin G was used to treat gonococcal infections up to the mid-1980s, until the emergence and spread of resistance rendered the antibiotic ineffective. These strains utilized either plasmid-mediated or chromosomally mediated mechanisms to become resistant to penicillin G (9, 36). The spread of strains harboring a plasmid-encoded TEM-like ␤-lactamase has been very rapid and has forced the withdrawal of penicillin for treating gonococcal infections in many areas. Chromosomally mediated resistance to penic...

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Insertion of a thymine (+T) in the 13 base pair inverted repeat of the Neisseria gonorrhoeae mtr promoter region and antibiotic susceptibility

Cited by 6 publications

References 6 publications

Relation between Genetic Markers of Drug Resistance and Susceptibility Profile of Clinical Neisseria gonorrhoeae Strains

Relation between Genetic Markers of Drug Resistance and Susceptibility Profile of Clinical Neisseria gonorrhoeae Strains

The Role of the Transcription Factors MtrR and MtrA in the Fitness of the Pathogen Neisseria gonorrhoeae

Genotyping as a Tool for Antibiotic Resistance Surveillance of Neisseria gonorrhoeae in New Caledonia: Evidence of a Novel Genotype Associated with Reduced Penicillin Susceptibility

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