Naresh Verma completed his PhD at the Department of Microbiology, University of Sydney in 1988. He has since pursued his research interests in microbial pathogenesis and vaccine development in post-doctoral fellowship appointments at the Karolinska Institute in Sweden and Howard Hughes Medical Institute at Stanford University, U.S.A. He returned to Australia to take up a lectureship at the ANU in 1993. He was awarded the Fellowship of the Australian Society for Microbiology (FASM) in 2005.

Contact Details

E: Naresh.Verma@anu.edu.au T: (+61 2) 6125 2666 F: (+61 2) 6125 0313

Main Research interests

Bacterial and bacteriophage genetics, and vaccine development.

Teaching Activities

BIOL2142: General Microbiology (Convenor) BIOL3141: Infection and Immunity BIOL3190: Medical Sciences Elective (Convenor)

Current Research Group

Angeline Josiah - Masters student Harris Korres - Postdoctoral Fellow Farzaana Thanweer - PhD student Anesh Nair - PhD student SweeSeong Tang - PhD student Roy Ramiscal - Hons student Divya George - M Biotech student Robert Stagg - PhD student Rebecca Barwick - PhD student Joana Moscoso - Masters student

Research Activities

Shigellae belong to the Gram-negative group of bacteria and are the causative agent of shigellosis or bacillary dysentery. The genus Shigella contains four species - S. dysenteriae, S. flexneri, S. boydii and S. sonnei. Two species in particular, S. dysenteriae type 1 and S. flexneri, cause acute diarrhoeal illness which often results in chronic infection especially in malnourished infants and children. Each year there are approximately 165 million cases of shigellosis throughout the world causing 1.1 million deaths. S. flexneri is the predominant species in endemic areas and the principal cause of morbidity and mortality in young children in developing countries. The infectivity of the disease is very high with oral-faecal person-to-person spread the most important mode of transmission. As hygiene standards and sanitary facilities in developing countries are not likely to improve in the near future, the development of effective vaccines is vital for the control and prevention of shigellosis. A number of approaches have been used in the past but no effective vaccine is available for prevention of shigellosis at present. S. flexneri is subtyped into various serotypes based on the combination(s) of antigenic determinants present in the O-antigen. Structural studies have shown that all S. flexneri O-antigens, except for serotype 6, are polymers of the basic tetrasaccharide repeating unit, which is found in S. flexneri serotype Y strains. Addition of glucosyl and/or O-acetyl residues to the basic O-antigen results in serotype conversion (O-antigen modification), which is mediated by temperate bacteriophages. The factors involved in O-antigen modification have been identified and characterised from these bacteriophages. We are interested in studying fundamental processes related to the O-antigen modification. Our group has shown that three integral membrane proteins (glucosyltransferases, Gtrs) are involved in this process. We have recently determined the topological structures of all three proteins encoded by the O-antigen modification gene cluster of phage SfV providing the basis for the identification of putative functional domains and essential residues. We are now investigating how these proteins function in the bacterial membrane and determine serotype specificity in S. flexneri. This information is being utilised to design a multivalent vaccine strain which would provide protection against shigellosis caused by different serotypes of S. flexneri. Little is known about the role, if any, that O-antigen modification plays in addition to generating antigenic variation. We are studying the effect that it and the serotype-converting phages have on the virulence characteristics of S. flexneri. We have isolated and partially characterised several serotype-converting phages from different S. flexneri serotype strains. We have recently sequenced the genome of bacteriophage SfV, which encodes the factors involved in type V O-antigen modification. Functional studies are now being carried out on various gene modules identified on SfV and other serotype-converting bacteriophages of S. flexneri. My group is also involved in identifying new virulence determinants and potential vaccine candidate antigens of Shigella spp using a proteomic approach.

Publications

Selected Publications 2009 Stagg, R., Tang, Swee-Seong, Carlin, N.,Talukder, K., Cam, P. and Verma, N. K. A novel glucosyltransferase involved in O-antigen modification of Shigella flexneri serotype 1c. Journal of Bacteriology (In Press). Linterman, M., Rigby, R.J., Wong, R., Silva, D., Withers, D., Anderson, G., Verma, N.K., Brink, R., Hutloff, A., Goodnow, C.C. and Vinuesa, C.G. (2009): Roquin differentiates the specialized functions of duplicated T cell co-stimulatory receptor genes Cd28 and Icos. Immunity 30, 2, 228-241. 2008 Farzaana Thanweer, Vikas Tahiliani, Haralambos Korres, Naresh K. Verma (2008): Topology and identification of critical residues of the O-acetyltransferase of serotype-converting bacteriophage, Sf6, of Shigella flexneri. BBRC (In Press). R. M. Stagg, P. D. Cam and N. K. Verma (2008)Identification of newly recognized serotype 1c as the most prevalent Shigella flexneri serotype in northern rural Vietnam. Epidemiology and Infection. 136, 1134-1140 Gosling, K.M., Goodnow, C.C., Verma, N.K. and Fahrer, A.M. (2008) Defective T cell function leading to reduced antibody production in a kleisin- mutant mouse. Immunology. Accepted Feb 2008.   Cam, P. D., Nguyen, Thi P. L., Smith, G. D. and Verma, N. K. (2008) Nitrate and bacterial contamination in well waters in Vinh Phuc province, Vietnam. Journal of Water and Health. 6, 275-278.[PubMed] 2007 Roberts, F., Allison, G. E. and Verma, N. K. (2007) Transcription termination mediated immunity and its prevention in bacteriophage SfV of Shigella flexneri. Journal of General Virology, 88, 3187-3197. Jennison, A. V. and Verma, N. K.  (2007) The acid resistance pathways of Shigella flexneri 2457T. Microbiology 153, 2593-2602. 2006 Korres, H. and Verma, N. K. (2006) Identification of essential loops and residues of Glucosyltransferase V (GtrV) of Shigella  flexneri.  Molecular Membrane Biology. 23, 407-419. Jennison, A.V., Raqib, R. and Verma, N.K. (2006) Immunoproteome analysis of soluble and membrane proteins of Shigella flexneri 2457T. World J Gastroenterol. 12, 6683-6688. Jennison, A. V., Roberts, F. and Verma, N. K. (2006) Construction of a multivalent vaccine strain of Shigella flexneri and evaluation of serotype-specific immunity. FEMS Immunol Med Microbiol. 46, 444-51. 2005 Lehane, A.M., Korres, H. and Verma N.K. (2005) Bacteriophage-encoded glucosyltransferase GtrII of Shigella flexneri : membrane topology and identification of critical residues. Biochemical J., 389, 137-143. Roberts, F., Jennison, A. and Verma, N.K. (2005) The Shigella flexneri serotype Y vaccine candidate SFL124 originated from a serotype 2a background. FEMS Immunology and Medical Microbiology , 45(2), 285-289 . Korres, H., Mavris, M., Morona, R., Manning, P. A. and Verma, N. K. (2005) Topological analysis of GtrA and GtrB proteins encoded by the serotype-converting cassette of Shigella flexneri. Biochemical and Biophysical Research Communications, 328, 1252-1260. 2004 Korres, H. and Verma, N. K. (2004) Topological analysis of glucosyltransferase GtrV of Shigella flexneri by a dual reporter system and identification of a unique reentrant loop. Journal of Biological Chemistry 279, 22469-22476. Jennison, A.V. and Verma, N.K. (2004). Shigella flexneri infection: pathogenesis and vaccine development. FEMS Microbiology Reviews 28, 43-58. Markine-Goriaynoff, N, Gillet, L, Etten, J, Korres, H., Verma, N. K. and Vanderplasschen, A. (2004). Glycosyltransferases encoded by viruses. Journal of General Virology, 85, 2741-2754. 2003 Allison, G.E., Angeles, D.A., Huan, P.T., Verma, N.K. (2003) Morphology of temperate bacteriophage SfV and characterisation of the DNA packaging and capsid genes: the structural genes evolved from two different phage families. Virology 308, 114-127. 2002 Walker, J.C. and Verma, N.K. (2002). Identification of a putativepathogenicity island in Shigella flexneri using subtractive hybridisation of the S. flexneri and Escherichia coli genomes. FEMS Microbiology Letters 213, 257-264. Allison, G.E., Angeles, D., Tran-Dinh, N. and Verma, N.K. (2002) The complete genome sequence of SfV, a serotype-converting temperate bacteriophage of Shigella flexneri. Journal of Bacteriology 184, 1974-1987. 2001 Adams , M.M., Allison, G.E. and Verma, N.K. (2001) Type IV O antigen modification genes in the genome of Shigella flexneri NCTC 8296. Microbiology 147, 851-860. 2000 Allison, G.E. and Verma, N.K. (2000) Serotype-converting bacteriophages and O-antigen modification in Shigella flexneri . Trends in Microbiology 8, 17-23. 1999 de Jersey, J., Bird, P.H., Verma N.K. and Bradley, M.P. (1999). Antigen-specific systemic and reproductive tract antibodies in foxes immunized with Salmonella typhimurium expressing bacterial and sperm proteins. Reproduction, Fertility and Development, 11, 219-228. Adhikari, P., Allison, G., Whittle, B. and Verma N.K. (1999). Serotype 1a O-antigen modification: molecular characterization of the genes involved and their novel organization in the Shigella flexneri chromosome. Journal of Bacteriology, 181, 4711-4718. Guan, S., Bastin, D.A. and Verma, N.K. (1999). Functional analysis of the O antigen glucosylation gene cluster of Shigella flexneri bacteriophage SfX. Microbiology, 145, 1263-1273.