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BRIEF COMMUNICATION
Year : 2008  |  Volume : 26  |  Issue : 2  |  Page : 158-159
 

Identification of weak points prone for mutation in ferredoxin of Trichomonas vaginalis


Department of Laboratory Medicine, Wiwanitkit House, Bangkhae, Bangkok 10160, Thailand

Date of Submission01-Jun-2007
Date of Acceptance26-Jun-2007

Correspondence Address:
V Wiwanitkit
Department of Laboratory Medicine, Wiwanitkit House, Bangkhae, Bangkok 10160
Thailand
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.40532

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 ~ 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


How to cite this article:
Wiwanitkit V. Identification of weak points prone for mutation in ferredoxin of Trichomonas vaginalis. Indian J Med Microbiol 2008;26:158-9

How to cite this URL:
Wiwanitkit V. Identification of weak points prone for mutation in ferredoxin of Trichomonas vaginalis. Indian J Med Microbiol [serial online] 2008 [cited 2019 Nov 14];26:158-9. Available from: http://www.ijmm.org/text.asp?2008/26/2/158/40532


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 Top


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

To identify the weak linkage in each protein, a new bioinformatic tool namely GlobPlot was used. Briefly, GlobPlot is a web service that allows the user to plot the tendency within the query protein for order/globularity and disorder. [6] The interface is straight forward to use, the user can put a sequence or enter the SWISS-PROT/SWALL accession or entry code. [6] In this work, the sequence derived from the previously described sequence searching was used as template for running of the GlobPlot. The GlobPlot server fetches the sequence and description of the polypeptide from an ExPASy server using Biopython.org software. [6] For determination, putative globular and disorder segments are selected using a simple peak finder algorithm known as PeakFinder. [6] The peaks are chosen when the first derivative shows positive (disorder) values over a continuous stretch of the minimum length. [6] With the described process, it successfully identifies inter-domain segments containing linear motifs and also apparently ordered regions that do not contain any recognised domain. [6] The identified motifs are the weak linkages in a protein which are prone for mutation. [6]


 ~ Results Top


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 Top


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 Top

1.Snipes LJ, Gamard PM, Narcisi EM, Beard CB, Lehmann T, Secor WE. Molecular epidemiology of metronidazole resistance in a population of Trichomonas vaginalis clinical isolates. J Clin Microbiol 2000;38:3004-9.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Das S, Huengsberg M, Shahmanesh M. Treatment failure of vaginal trichomoniasis in clinical practice. Int J STD AIDS 2005;16:284-6.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Mammen-Tobin A, Wilson JD. Management of metronidazole-resistant Trichomonas vaginalis: A new approach. Int J STD AIDS 2005;16:488-90.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Quon DV, d'Oliveira CE, Johnson PJ. Reduced transcription of the ferredoxin gene in metronidazole-resistant Trichomonas vaginalis. Proc Natl Acad Sci USA 1992;89:4402-6.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Lee C, Wang Q. Bioinformatics analysis of alternative splicing. Brief Bioinform 2005;6:23-33.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Linding R, Russell RB, Neduva V, Gibson TJ. GlobPlot: Exploring protein sequences for globularity and disorder. Nucleic Acids Res 2003;31:3701-8.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber GE. Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis. Clin Microbiol Rev 2004;17:783-93.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Dunne RL, Dunn LA, Upcroft P, O'Donoghue PJ, Upcroft JA. Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis. Cell Res 2003;13:239-49.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Quon DV, d'Oliveira CE, Johnson PJ. Reduced transcription of the ferredoxin gene in metronidazole-resistant Trichomonas vaginalis. Proc Natl Acad Sci USA 1992;89:4402-6.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]


    Figures

  [Figure - 1]

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