Department of Biotechnology & Bioinformatics, University of Hyderabad, India Pathogen Biology Laboratory

Dr Niyaz Ahmed BVSc MS PhD

Associate Professor and Group Leader

Editor-in-Chief, Gut Pathogens | Member - PLOS International Advisory Group

Dr Ahmed graduated in Veterinary Medicine in 1995 (Nagpur) and obtained further degrees in Animal Biotechnology (MS) (NDRI, Karnal) and a PhD (Manipal University) in Molecular Infectious Diseases. He joined CDFD in Hyderabad as a tenured faculty member (Staff Scientist) in 1998. In December 2008 he relocated to the University of Hyderabad as Associate Professor of Biotechnology and since then has been involved in graduate teaching and research supervision at the School of Life Sciences. Dr Ahmed's current research interests include genomics, evolution and molecular pathogenesis of the two co-evolved human pathogens, namely, Mycobacterium tuberculosis and Helicobacter pylori, in the context of evolution of adaptation mechanisms, and acquisition and optimization of virulence during colonization/infection. Ahmed also has interest in comparative genomics of bacterial pathogens obtained from different epidemics as well as single patients at different occasions and this approach nurtures the concepts of ' chronological evolution' and 'replicative genomics' as tools to study host-microbe interaction over time. In 2009, Ahmed initiated a new and vibrant group/laboratory at the University of Hyderabad which currently encompasses a research group of 16 full time PhD students and also supports an Indo-German International Research Training Group on Functional Molecular Infection Epidemiology (GRK1673). Research in Ahmed lab is funded by the Department of Biotechnology of the Indian Government and partly through the internal support of the University of Hyderabad. Recently, Ahmed was conferred with the National Bioscience Award of India for the year 2011.

Research contributions statement:

'Combining the rigours of molecular epidemiology/genomics and cell signaling/immunology, Dr Ahmed's group has uniquely contributed to the analysis of geographical gene pools and virulence mechanisms of some of the chronic pathogens, namely, enteropathogenic bacteria and Mycobacterium tuberculosis with reference to transmission dynamics and novel bacterial strategies of survival, adaptation and persistence'.

Research summary:

Dr Ahmed’s research group has over the last few years sequenced and finished complete genome sequences of about two dozen unique isolates of H. pylori entailing spectrum of gastric diseases and originating from different patient populations. These high resolution and high throughoput genome data were used to expand the H. pylori pangenome and understand the exact boundaries and constitutents of the plasticity region cluster of H. pylori that have been traditionally assumed to contain several novel genes imparting virulence based fitness advantage to the pathogen. Apart from plasticity, the conserved genomic information was systematically used to analyze genome evolution patterns of more than four hundred distinct Helicobacter isolates to dissect natural history in the context of peopling and human anthropology in Peru and in India (representatives of the two vast continents that have witnessed multiple waves of human migrations in the neolithic times and in the recent past). (Ahmed N et al., 2008. Nature Rev Microbiol. 6:387-94; Devi SM et al.,2006. BMC Genomics 7:191; Devi SM et al., 2007. BMC Genomics 8:184). The major observation comprised of the Indian H. pylori’s ancestral relationships with the western isolates. This has bearing on our understanding of the host – pathogen coevolution and co-migration. Similarly, they have developed and maintained a rigorous model of chronological evolution of the genome in the form of serial isolates of H. pylori obtained from different niches of the stomach of a single patient, obtained across a decade. These isolates have been profiled using whole genome microarrays, pan-island sequencing and full genome Illumina sequencing; parts of the pathogenicity islands have been found to rearrange over time. Interestingly these rearrangements did not bring change in pathological severity of the disease meaning that interplay of several unknown virulence factors is possible (Prouzet-Mauleon et al., 2005. J Clin Microbiol 43:4237-4241 and Alvi et al., 2007. J Clin Microbiol. 45:4039-4043). Whole genome sequences of these isolates have now been completed by the authors (GenBank Genomes IDs: CP002184, CP002571, CP002572) and these genomes are viewed as an invaluable tool in understanding chronological evolution of H. pylori and have a great bearing on the understanding of pathogen survival and adaptation through genomic recasting (Devi et al., 2010 J Bacteriol; Avasthi et al., 2011 J Bacteriol). Further, a series of putative virulence factors have been gleaned from the revised annaotated plasticity region cluster and were functionally characterized by Dr Ahmed including those from the core (Hussain et al., 2008. PLoS ONE 3:e1481) and the flexible genome compartments (Rizwan et al., 2008. J Bacteriol. 190:1146-1151; Alvi et al., 2011, PLoS ONE, 6(7): e22530). Important among these are the virulence factors encoded by the genomic plasticity region genes which constitute a putative type IV secretion system, acquired horizontally. Two of these virulence factors (JH940 and HP986) potentially interacted with the human immune system. The HP986 appears to be involved in Helicobacter persistence. Most persistent microbes seemingly evolve strategies to foil host responses and gain niche. However, it seems that there is fine tuning between microbial immune evasion and maintenance of the growth fitness. For example, H. pylori both downregulates T-cell responses through the VacA mediated cell cycle arrest, and upregulates mucosal proinflammatory pathways by CagA. Interestingly in Ahmed’s studies, HP986 appears to be able to perform both the immune stimulatory and immune evasion tasks single handedly (Alvi et al., 2011, PLoS ONE, 6(7): e22530).

Community recognition and translational impact:

Dr Ahmed’s work based on adaptive evolution of single H. pylori strains in individual stomachs over extended periods of colonization has given impetus to the emerging field of ‘chronological evolution’ (Prouzet-Mauleon et al., 2005, J Clin Microbiol; Alvi et al., 2007, J Clin Microbiol). Recently, Dr Ahmed’s group has ushered into the next generation sequencing of pathogenic bacteria and has completed whole genome sequences of the three H. pylori isolates hierarchically obtained from a single patient (Devi et al., 2010 J Bacteriol; Avasthi et al., 2011 J Bacteriol) this is especially relevant to the adaptation mechanisms of chronic pathogens such as H. pylori. The H. pylori research community is enthusiastic about this contribution and that these genomes will form basis for a new discipline of ‘replicative genomics’ of pathogens in single patients in future studies (Ahmed N, 2010 Gut Pathogens). Technologically, this work has potential implications for genetic stability testing of live bacterial vaccine canddates during colonization. This work has resulted in important funding instruments and collaborative networks as follows:

1. Indo-German IRTG 1673: An International Network of Excellence funded by the German Research Foundation wherein Dr Ahmed is the Speaker (Sprecher) from the Indian side (2010-2014).

2. University of Malaya High Impact Research Grant – Molecular Genetics (Dr Ahmed is the Principal collaborator also with Prof. Barry J. Marshall, Nobel Laureate) (2010-2015).

3. Department of Biotechnology, GOI: Helicobacter pylori genome program under the Infection Biology Task Force (beginning 2013).

4) Marie Curie Actions IRSES project under the 7th Framework program of the European Commission - INDOEUROPEAN-MATHDS - 'Mathematics in Health and Disease' wherein Dr Ahmed is a Principal Investigator from Indian side.

Another work of Dr Ahmed and colleagues demonstrating population structure of M. tuberculosis in India (Ahmed et al., 2004 J Clin Microbiol) and that the ancestral strains of M. tuberculosis are predominant in this part of the country (Gutierrez+Ahmed et al., 2006 Emerg Infect Dis) led to the popular working hypothesis that these ancestral strains could be more responsive to antitubercular therapy because of their possible adaptive evolution. Studies have been designed to validate this, especially, the treatment success rates under DOTS program in India are highly suggestive of this possibility (WHO Report on TB, 2010). In appreciation of this fact, the Department of Biotechnology, Government of India has established a Centre of Excellence on tuberculosis (CoE TB) in Hyderabad wherein Dr Ahmed’s studies form an important component.

Dr Ahmed has completed 25 important bacterial genome projects so far, thus contributing a vast body of bacterial whole genome sequence data in to the federated/public databases. These genomes are widely downloaded, used as reference for comparative genomics and cited in a large number of publications. Following are the important bacterial genomes contributed/completed by Dr Ahmed:

1) Complete genome of H. pylori strain 908 (NCBI Bioproject PRJNA50869, Accession ID: CP002184)

2) Complete genome of H. pylori strain 2017 (NCBI Bioproject PRJNA62769, Accession ID: CP002571)

3) Complete genome of H. pylori strain 2018 (NCBI Bioproject PRJNA62771, Accession ID: CP002572)

4) Complete genome of H. pylori strain NAB47 (NCBI Bioproject PRJNA85617, Accession ID: AJFA02000000)

5) Complete genome of H. pylori strain NAD1 (NCBI Bioproject PRJNA85619, Accession ID: AJGJ02000000)

6) Complete genome of S. enterica ser. Typhi strain BL196 (NCBI Bioproject PRJNA190361, Accession ID: AJGK00000000)

7) Complete genome of Paracoccus denitrificans strain SD1 (NCBI Bioproject:PRJNA68425, Accession ID: AJFB00000000)

8) Complete genome of S. enterica ser. Typhi strain Papua NG1 (NCBI Bioproject: PRJNA190370, Accession ID: AJTE00000000)

9) Complete genome of S. enterica ser. Typhi strain Papua NG2 (NCBI Bioproject: PRJNA190369, Accession ID: AJTD00000000)

10) Complete genome of S. enterica ser. Typhi strain Kelantan2 (NCBI Bioproject: PRJNA190381, Accession ID: AKIC00000000)

11) Complete genome of M. tuberculosis NA-A0008 (ancestral1) (NCBI Bioproject: PRJNA168604, Accession ID: ALYG00000000)

12) Complete genome of M. tuberculosis NA-A0009 (ancestral2) (NCBI Bioproject: PRJNA168605, Accession ID: ALYH00000000)

13) Complete genome of Multiresistant, uropathogenic E. coli NA114 (NCBI Bioproject: PRJNA6697, Accession ID: CP002797)

14) Complete genome of Vibrio parahemolyticus PCV08-7(NCBI Bioproject: PRJNA185026, Accession ID: AOCL00000000)

15) Helicobacter pylori UM018 from an Indian origin patient (Bioproject ID: PRJNA187431, Accession ID: AONK00000000)

16) Helicobacter pylori UM034 from Indian origin patient (Bioproject ID: PRJNA187437, Accession ID: AONN00000000)

17) Helicobacter pylori UM054 from Chinese patient (Bioproject ID: PRJNA187433, Accession ID: AONL00000000)

18) Helicobacter pylori UM007 from Chinese patient (Bioproject ID: PRJNA187435, Accession ID: AONM00000000)

19) Helicobacter pylori UM045 from Malay patient (Bioproject ID: PRJNA187438, Accession ID: AONO00000000)

20-25) Six Genomes of mouse adapted Helicobacter pylori analyzed as a part of an ongoing vaccine trial

Current international collaborators:

Leonardo A. Sechi, Lothar H. Wieler, Astrid Lewin, Hortense Slevogt, Thomas Meyer, Francis Megraud, Barry J Marshall, Mohammed Benghezal, Carmen Molina-Paris, Rudy A. Hartskeerl, Andreas Hensel, Jamuna Vadivelu, Subha Bhassu, Kwai-Lin Thong

Current PhD Students:

Current post-docs:

Peddireddy Vidyullatha | Banaganapalli B Shaik

Past post-docs and Ahmed Lab alumni (this lab and erstwhile at CDFD):

K Rajender Rao (currently faculty at NIN Hyderabad), Athar H. Siddiqui (currently faculty at UoH Hyderabad), Prashant Kenchappa (currently faculty at Pondicherry University India), Shaik Mahaboob Ali (currently faculty at Lepra-Blue Peter Institute Hyderabad), Mohammed Rizwan Qureshi (currently faculty at Jazan University), Ayesha Alvi (currently faculty at Jazan University), S. Haritha Devi (currently post-doc at CCMB Hyderabad), S. Asif Hasan (currently faculty at King Abdul Aziz University), S Manjulata Devi (currently at CFTRI Mysore).

Select publications: [See all publications of Dr Ahmed]

Ahmed N, Dobrindt U, Hacker J and Hasnain SE. Genomic fluidity and pathogenic bacteria: applications in diagnostics, epidemiology and intervention. Nature Rev Microbiol 2008; 6:387-394. (download PDF)

Hussain A, Ewers C, Nandanwar N, Guenther S, Jadhav S, Wieler LH, Ahmed N. Multi-resistant uropathogenic Escherichia coli from an endemic zone of urinary tract infections in India: genotypic and phenotypic characteristics of ST131 isolates of the CTX-M-15 Extended-Spectrum-Beta-Lactamase producing lineage. Antimicrob. Agents Chemother. 2012; 56:6358-65. (download PDF)

Kumar A, Majid M, Kunisch R, Rani PS, Qureshi IA, Lewin A, Hasnain SE, Ahmed N. Mycobacterium tuberculosis DosRRegulon Gene Rv0079 Encodes a Putative, 'Dormancy Associated Translation Inhibitor (DATIN)'. PLOS ONE 2012; 7:e38709. (read article)

Saini V, Raghuvanshi S, Khurana JP, ... Ahmed N,.. Massive gene acquisitions in Mycobacterium indicus pranii provide a perspective on mycobacterial evolution. Nucleic Acids Res. 2012; 40:10832-10850. (read article)

Alvi A, Ansari SA, Ehtesham NZ, Rizwan M, Devi S, Sechi LA, Qureshi IA, Hasnain SE, Ahmed N. Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986) points to its role in chronic persistence. PLOS ONE 2011;6(7):e22530. (read article)

Avasthi TS, Devi SH, Taylor TD, Kumar N, Baddam R, Kondo S, Suzuki Y, Lamouliatte H, Mégraud F, Ahmed N. Genomes of two chronological isolates (Helicobacter pylori 2017 and 2018) of the West African Helicobacter pylori strain 908 obtained from a single patient. J Bacteriol. 2011; 193:3385-1386. (read article).

Rizwan M, Alvi A, Ahmed N. Novel protein antigen (JHP940) from the genomic plasticity region of Helicobacter pylori induces tumor necrosis factor alpha and interleukin-8 secretion by human macrophages. J Bacteriol. 2008; 190(3):1146-51. (read article).

Devi SM, Ahmed I, Francalacci P, Hussain MA, Akhter Y, Alvi A, Sechi LA, Mégraud F,Ahmed N. Ancestral European roots of Helicobacter pylori in India. BMC Genomics 2007; 8:184 (read article).

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