ABSTRACT
The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp. Newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) were designed in a targeted fashion to increase antibacterial activity, in some cases through secondary mechanisms of action. Resistance to the glycopeptides emerged in delayed fashion and occurs via a spectrum of chromosome- and plasmid-associated elements that lead to structural alteration of the bacterial cell-wall precursor substrates.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cell Wall/metabolism , Drug Resistance, Bacterial , Glycopeptides/pharmacology , Anti-Bacterial Agents/chemistry , Glycopeptides/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Vancomycin-Resistant Enterococci/drug effectsABSTRACT
Gardnerella vaginalis is associated with bacterial vaginosis (BV), the most common cause of vaginal discharge. Metronidazole is a front-line therapy for BV, and treatment failure and recurrent disease are common problems. Whole-genome sequencing studies have revealed that G. vaginalis has a population structure that consists of 4 clades: clades 1 and 3 are associated with BV, whereas clades 2 and 4 are not. To determine if metronidazole susceptibility is associated with population structure, we analyzed 87 clinical isolates and found that metronidazole resistance (MIC ≥32 µg/mL) was highly associated with clade (P<0.0001), as 14/14 clade 3 isolates (100%) and 22/22 clade 4 isolates (100%) exhibited resistance, compared to only 16/37 clade 1 isolates (35%) and 1/14 clade 2 isolates (7.1%). The identification of intrinsically metronidazole-resistant G. vaginalis clades will facilitate future studies on the relationship between metronidazole resistance and BV treatment failure.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Gardnerella vaginalis/drug effects , Gardnerella vaginalis/isolation & purification , Genotype , Metronidazole/pharmacology , Female , Gardnerella vaginalis/classification , Gardnerella vaginalis/genetics , Gram-Positive Bacterial Infections/microbiology , Humans , Microbial Sensitivity Tests , Vaginosis, Bacterial/microbiologyABSTRACT
We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to ≥500 µg/ml. Two coding changes, in genes encoding a response regulator and an NAD(+) synthetase, arose during selection.
ABSTRACT
We report the draft genome sequence of a vaginal isolate of Atopobium vaginae vaginae (strain 44061), an organism linked to bacterial vaginosis (BV), the most common gynecological infection in the United States. This species is often highly resistant to metronidazole, which is a front-line therapy for BV. Strain 44061 is a metronidazole-susceptible isolate (MIC, 16 µg/ml), and its genome sequence will be useful for comparative studies to elucidate the molecular basis of metronidazole resistance in this species.
ABSTRACT
We report the draft genome sequence of a Gardnerella vaginalis strain (3549624) isolated from a vaginal specimen. G. vaginalis is associated with bacterial vaginosis, the most common cause of vaginal discharge, which is often treated with metronidazole. This isolate is highly resistant to metronidazole (MIC, 500 µg/ml) and may be useful for comparative genomic studies to determine the molecular basis of metronidazole resistance in this species.
ABSTRACT
Metronidazole resistance in the sexually transmitted parasite Trichomonas vaginalis is a problematic public health issue. We have identified single nucleotide polymorphisms (SNPs) in two nitroreductase genes (ntr4Tv and ntr6Tv) associated with resistance. These SNPs were associated with one of two distinct T. vaginalis populations identified by multilocus sequence typing, yet one SNP (ntr6Tv A238T), which results in a premature stop codon, was associated with resistance independent of population structure and may be of diagnostic value.
Subject(s)
Metronidazole/pharmacology , Nitroreductases/genetics , Protozoan Proteins/genetics , Trichomonas vaginalis/drug effects , Trichomonas vaginalis/genetics , Antiprotozoal Agents/pharmacology , Codon, Terminator/genetics , Drug Resistance/genetics , Parasitic Sensitivity Tests , Polymorphism, Single NucleotideABSTRACT
Candida species are responsible for many opportunistic fungal infections. Fluconazole is a well-tolerated antifungal drug, commonly used in the treatment of candidiasis. However, with fluconazole resistance ever increasing, rapid detection and antifungal susceptibility testing of Candida is imperative for proper patient treatment. This paper reports a cost-effective, simple and rapid chromogenic agar dilution method for simultaneous Candida species identification and fluconazole susceptibility testing. The results obtained by X-Plate Technology were in absolute concordance with standard microbroth dilution assays. Analysis of 1383 clinical patient samples with suspected vulvovaginal candidiasis revealed that this technology was able to detect and speciate the Candida isolate and determine the fluconazole susceptibility. The prevalence and susceptibility profiles of the clinical isolates using this method were highly similar to published reports using the microbroth dilution method.
Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Fluconazole/pharmacology , Microbial Sensitivity Tests/methods , Candida/classification , Chromogenic Compounds/chemistry , Colony Count, Microbial , Cost-Benefit Analysis , Culture Media/chemistry , Drug Resistance, Fungal , Humans , Microbial Sensitivity Tests/economics , Microbial Sensitivity Tests/standardsABSTRACT
A multiplex PCR assay was used to detect the erythromycin (EM) and clindamycin (CM) antibiotic resistance genes, ermB, ermTR, and mefA/E, in Group B Streptococcal (GBS) clinical isolates and in DNA extracted from the corresponding cervicovaginal-rectal (CVR) swabs. We compared these results to the standard EM/CM double disk diffusion assay of 46 isolates. Given that these genes are present in other CVR flora and are found on mobile genetic elements, the PCR assay was unable to predict GBS resistance directly from the swabs. Therefore, PCR can only accurately detect resistance genes and predict the resistance phenotype from purified GBS isolates.
Subject(s)
Anti-Bacterial Agents/pharmacology , Clindamycin/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Erythromycin/pharmacology , Streptococcus agalactiae/drug effects , Cervix Uteri/microbiology , Disk Diffusion Antimicrobial Tests , Female , Genes, Bacterial , Humans , Polymerase Chain Reaction , Rectum/microbiology , Streptococcus agalactiae/genetics , Streptococcus agalactiae/isolation & purification , Vagina/microbiologyABSTRACT
Erythromycin (EM) and clindamycin (CM) susceptibility testing was performed on 222 clinical isolates of group B Streptococcus. A multiplex PCR assay was used to detect the ermB, ermTR, and mefA/E antibiotic resistance genes. These results were compared to the phenotypes as determined by the standard EM/CM double disk diffusion assay.