In Silico Identification of Novel Candidate Drug Targets in Haemophilus Influenzae Rd KW20
International Journal of Genetics and Genomics
Volume 2, Issue 4, August 2014, Pages: 62-67
Received: Jul. 21, 2014;
Accepted: Aug. 7, 2014;
Published: Aug. 20, 2014
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Ranjith Kumavath, Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, P.O. Central University, Kasaragod- 671314, India
Swaraj Prasad, Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, P.O. Central University, Kasaragod- 671314, India
Pratap Devarapalli, Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, P.O. Central University, Kasaragod- 671314, India; Genomics & Molecular Medicine Unit, Institute of Genomics and Integrative Biology Council of Scientific and Industrial Research, Mathura Road, New Delhi-110025, INDIA
Debmalya Barh, Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, PurbaMedinipur, West Bengal-721172, INDIA
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Background: Globally, respiratory diseases cause an estimated 1.9 million deaths per year. One of the most important aetiological organisms of both adult and childhood respiratory disease is Non-Typeable Haemophilus influenzae (NTHi). NTHi is frequently isolated from the respiratory tract during episodes of sinusitis, Otitis Media and pneumonia and is the most common cause of Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis exacerbations. Methods: The work has been effectively complemented with the compilation of the Database of Essential Genes (DEG) of H. influenzae Rd KW20. Each protein is subjected to BLASTP in NCBI server http://www.ncbi.nlm.nih.gov/blastp. The candidate drug targets are determined by KAAS (KEGG Automatic Annotation Server), KEGG ORTHOLOGY and KEGG GENES. Results: The given gram negative bacteria H. influenzae Rd KW20 has six distinguished domains i.e., cytoplasmic, cytoplasmic membrane, periplasmic, outer membrane, extracellular and unknown domains. Out of 642 essential genes, the predicted non-human Homologous are 412 in the different domain of given bacteria. With the help of KAAS (KEGG Automatic Annotation Server), KEGG ORTHOLOGY and KEGG GENES, we successfully identified 35 novel drug targets which have common metabolic pathways both in host and pathogen & pathogen specific metabolic pathways. Conclusion: The novel drug targets suggest those genes which are active in both the host and pathogen metabolic pathway and should be a pathogen specific metabolic pathway. The important drug target regions are vacJ, lepB, emrB, MurG & dgkA. vacJ is present in outer membrane while lepB, emrB, MurG&dgkA are present in cytoplasmic membrane. All these genes are fully sequenced and specifically annotated in KEGG PATHWAY.
NTHi (Non-Typeable H. Influenzae), NP (Non-Typeable) , DEG (Database of Essential Genes), Rd (Rough Derivative), ChoP (Phosphorylcholine), COPD (Chronic Obstructive Pulmonary Disease), SVM (Support Vector Machine), SCL (Subcellular Localization)
To cite this article
In Silico Identification of Novel Candidate Drug Targets in Haemophilus Influenzae Rd KW20, International Journal of Genetics and Genomics.
Vol. 2, No. 4,
2014, pp. 62-67.
Martin K, Morlin G, Smith A, Nordyke A, Eisenstark A, Golomb M. The tryptophanase gene cluster of Haemophilus influenzae type b: evidence for horizontal gene transfer. J Bacteriol 1998; 80:107–18.
Teele DW, Klein JO, Chase C, Menyuk P, Rosner BA, the Greater Boston Otitis Media Study Group. Otitis Media in infancy and intellectual ability, school achievement, speech, and language at age 7 years. J Infect Dis 1990; 162:685–94.
Sukupolvi SP, Grass S, Geme St III JW. The H. influenzae Type b hcsA and hcsB gene products facilitate transport of capsular polysaccharide across the outer membrane and are essential for virulence. J Bacteriol 2006; 188: 3870-7.
Van SMH, Van LA, Mooi FR, Van JP. Contribution of the major and minor subunits to fimbria-Mediated adherence of H. influenzae to human epithelial cells and erythrocytes. Infect Immun 1995; 63: 4883-9.
Hendrixson DR, Geme III JWS. Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein. Mol Cell 1998; 2: 841-50.
Murley YM, Edlind TD, Plett PA, LiPuma JJ. Cloning of the haemocin locus of H. influenzae type b and assessment of the role of Haemocin in virulence. Microbiology 1998; 144:2531-8.
Duim B, Vogel L, Puijk W, Jansen HM, Meloen RH, Dankert J, et. al. Fine mapping of outer membrane protein P2 antigenic sites which vary 55 during persistent infection by Haemophilus influenzae. Infection and immunity 1996; 64:4673-79.
Gray-Owen SD, Loosmore S, Schryvers AB. Identification andcharacterization of genes encoding the human transferrin-binding proteins from Haemophilus influenzae. Infection and immunity 1995; 63:1201-10
Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute Otitis Media caused by both Streptococcus pneumonia and non-typable H. influenzae: a randomised double-blind efficacy study. Lancet 2006; 367:740-8.annotation and pathway reconstruction server. Nucleic Acids Research 2007; 35:W182–5.
Gardy JL, Brinkman FSL. Methods for predicting bacterial protein subcellular localization. Nature Publishing Group 2006; 4:741-51.
Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22(13):1658-9.
Barh, D.&Misra, N.A. In silico identification of membrane associated candidate drug targets in Neisseria gonorrhoeae. IJIB 2009; 6(2):65-7.
Haung J, O’Tole WP, Shen W, Amrine-Madsen H, Jiang X, Lobo N, et al. Novel chromosomally encoded multidrug efflux transporter mdea in Staphylococcus aureus. Antimicrob Agents Chemother 2004; 48(3):909–17.
Ha S, Gross B, Walker S. E. Coli MurG: A Paradigm for a Superfamily of Glycosyltransferases. Current Drug Targets Infectious Disorders 2001; 1(2):201-13.
Suzuki T, Murai T, Fukuda I, Tobe T, Yoshikawa M, Sasakawa C. Identification and characterization of a chromosomal virulence gene, vacJ, required for intercellular spreading of Shigella flexneri. Molecular Microbiology 1994; 11 (1):31-41.