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Indian Journal of Medical Microbiology, Vol. 26, No. 2, April-June, 2008, pp. 158-159 Brief Communication Identification of weak points prone for mutation in ferredoxin of Trichomonas vaginalis Wiwanitkit V Department of Laboratory Medicine, Wiwanitkit House, Bangkhae, Bangkok 10160 Date of Submission: 01-Jun-2007 Code Number: mb08045 Abstract Trichomonas vaginalis , the causative agent for human trichomoniasis, is a problematic sexually transmitted disease mainly in women. At present, metronidazole-resistant trichomoniasis is an infrequent but challenging problem with no universally successful treatment. Genetic mutation is believed to be an important factor leading to increasing drug resistance. Understanding the mutation status will help to design accurate strategies of therapy against mutant strains of T. vaginalis . The author performed a bioinformatic analysis to determine positions that tend to comply peptide motifs in the amino acid sequence of ferridoxin of T. vaginalis . Based on this study, the weak linkages in the studied protein can be identified and can be useful information for prediction of possible new mutations that can lead to drug resistance. In addition, the results from this study can be good information for further research on the diagnosis for mutants and new effective drug development.Keywords: Ferridoxin, mutation, Trichomonas vaginalis Trichomonas vaginalis , the causative agent for human trichomoniasis causes sexually transmitted disease mainly in women, where it may be asymptomatic or cause severe vaginitis and cervicitis. [1] Drug resistance to T. vaginalis results from a single or very few mutational events. [1] Das et al., proposed that the prevalence of non-response to standard doses of metronidazole without any history of reinfection or nonadherence was 1.7% and has significantly increased from 0.38% in 1999 to 3.5% in 2002. [2] At present, metronidazole-resistant trichomoniasis is an infrequent but challenging problem with no universally successful treatment. [3] Quon et al., suggested a strong correlation between drug resistance and altered regulation of ferredoxin gene transcription. [4] A reduction in gene transcription results in decreased intracellular levels of ferredoxin and this may play a role in metronidazole resistance by decreasing the ability of the cell to activate the drug. [5] Generally, disordered regions in proteins often contain short linear peptide motifs that are important for protein function. Identification of the peptide motifs in the amino acid sequence can give a good prediction for the weak linkages in a protein. [5] In this study, the author performed a bioinformatic analysis to determine the positions that tend to comply peptide motifs in the amino acid sequence of ferredoxin. Materials and Methods The database PubMed was used for searching for the amino acid sequence of ferredoxin of T. vaginalis . Pubmed poses a curated protein sequence database which strives to provide a high level of annotation (such as the description of the function of a protein, its domains structure, post-translational modifications, variants, etc.). The derived sequences were used for further study on weak linkage. Identification of weak linkage in each protein Results Ferredoxin (EAY12184) of T. vaginalis was analysed by GlobPlot. All identified positions are presented in the figure. The identified hot spot regions were 43-48.Discussion In many infectious diseases, the structural aberration is believed to be the main cause of failure in diagnosis and disease control. Some disorders are mentioned as a single substitution with other effects on the sequence frame, the others are mentioned as a frameshift. Resistance to metronidazole can be seen in clinical practice. The mutations in genomic level are the important cause of drug resistance phenomenon.At least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug. [7] The lack of approved alternative therapies for T. vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease. [7] The mechanism of metronidazole resistance in T. vaginalis from treatment failures is not well understood, unlike resistance which is developed in the laboratory under increasing metronidazole pressure. [8] Genetic mutation is believed to be an important factor leading to increasing drug resistance problem. Recently, Quon et al. reported that sequence comparison of the region 5′ of the ferredoxin gene among drug-sensitive and -resistant strains revealed two point mutations, at -178 and -239 nucleotides relative to the start of transcription, in a resistant strain. [9] Understanding the mutation status will help to design accurate strategies of therapy against mutant strain T. vaginalis . Here, the author used an algorithm to identify the position in the amino acid sequences of ferredoxin from T. vaginalis that can be mutated. He could identify many positions. Some are known positions and the others are newly discovered. Based on this study, the weak linkages in the studied protein can be identified and can be good information for expectation of possible new mutations that can lead to drug resistance. In addition, the results from this study can be good information for further research on the diagnosis for mutants and new effective drug development. References
Copyright 2008 - Indian Journal of Medical Microbiology |
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