Pathogen Biology Lab (UoH); Laboratory of Molecular and Landscape Epidemiology (icddr,b)

Our research interests and current focus of the labs at Hyderabad and Dhaka:

Our group’s contributions are severally and internationally accepted in the context of Functional Molecular Infection Epidemiology of bacterial pathogens.

Dr Ahmed’s research groups have over the last several years systematically deciphered molecular epidemiology based on genome dynamics of pathogens namely H. pylori, M. tuberculosis and enteropathogens entailing spectrum of human diseases occurring in geographically distinct patient populations (Ahmed et al., 2008. Nature Rev Microbiol. 6:387-94; Kumar et al, 2015. Nucleic Acids Res. 43:324-35; Baddam et al., 2014. Scientific Reports 4:7457).

(Dr Ahmed administering the pledge of ‘Rashtriya Ekta Diwas’ – National Unity Day)

Dr Ahmed used clinical, genomics and demographic data on an epidemiological platform to define the H. pylori pan genome in an evolutionary context and to understand the boundaries and vertices of the plasticity region cluster of H. pylori that has been traditionally assumed to shape and shelter 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 different countries (Kumar et al., 2015. Nucleic Acids Res. 43:324-35, 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). Some of the major observations from these pioneering studies of Dr Ahmed comprised of the Indian H. pylori’s ancestral relationships with the western isolates and that H. pylori in some multiethnic settings such as Malaysia evolve and adapt in a host specific manner. This has bearing on our understanding of the host – pathogen coevolution and co-migration.

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Group activity – proof reading and copy editing

Similarly, Dr Ahmed’s group has developed and maintained a rigorous model of chronological evolution of a bacterial genomes in the form of serial isolates of H. pylori obtained from different niches of the stomach of a single patient, obtained across a decade (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 have been viewed by the community 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.

Lab group 2013

Lab group 2013

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). Apart from this, Dr Ahmed has been actively pursuing molecular epidemiology of acquisition and propagation of drug resistance and fitness/survival advantage in human enteric pathogens such as enteropathogenic and uropathogenic E. coli and Salmonella enterica. This work provided novel insights into aspects of the fitness advantage of E. coli lineage ST131 and suggested that a number of factors are likely involved in the worldwide dissemination of and infections due to ST131 E. coli isolates (Hussain et al., 2014 Antimicrob Agents Chemother. 58:7240-9; Hussain et al., 2012 Antimicrob Agents Chemother. 56:6358-65) as well as survival mechanismsm of other enteric bacteria obtained from endemic settings of Asia (Baddam et al., 2014. Scientific Reports 4:7457).

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Group celebrating birthday of Jan Berghoefer

Current Lab Members in Hyderabad:

1) Y. Priyadarshini – PhD scholar

2) Shamsul Qumar – PhD student

3) Majid Ahmed Saleh Qaria – PhD student (International)

4) Kishore Nalam – PhD student

5) Arya Suresh – PhD student

Group and studies in icddr,b, Dhaka:

Nearly 200 researchers, clinicians and paramedical staff as well as technicians form Dr Ahmed’s extended team at the icddr,b.

a) Due to a strong seasonal nature of cholera epidemics and the reservoirs and drivers of the disease linking to climate change, there is a strong potential and significance of using climatic and incidence data in conjunction with AI to develop a rationale and technology platform for advanced prediction of the outbreaks. Given this, our group in Dhaka is applying AI algorithms to understand the dynamics of cholera disease and the role of climatic factors which can further guide us on building an efficient early warning system of surveillance active in real time. Such a system would be able to provide the valuable information in advance to the relevant authorities and their prompt action in mobilizing the necessary medical resources such as preemptive vaccination drives. This work is supported by Microsoft Inc. through AI for Earth program.

b) Antibiotic/antimicrobial resistance (AMR) is on the rise, globally, and is regarded as a critical, multi-sectoral issue that has real implications for human health. Big data of bacterial genomes available on federated open access archives hold locked information entailing genomic mechanisms shaping AMR in bacteria. Our new studies strive to unlock and glean those data in order to determine new genomic mechanisms of bacterial fitness that possibly operate at the interface of their human and animal hosts and the environment. The publicly available genome data of about 4000 different bacterial organisms is currently being analyzed and annotated using gene prediction tools operationalized through Microsoft Azure platform and Azure machine learning approaches in order to compute novel gene content codifying fitness functions such as AMR. The project is translational and data/resource intensive and is likely to deliver important solutions for healthcare management including new paradigms of AMR surveillance.  This work is supported by icddr,b core grants and through the Microsoft Azure for Research Award in Public Health.

icddrb-group

Alumni of the lab(s) who completed their PhD with Dr Ahmed as supervisor:

1) Dr. Shivendra Tenguria  (Post-doctoral Fellow, Food Sciences, Purdue University, USA)

2) Dr. Suhail A Ansari (Post-doctoral Fellow, Bilkent University, Ankara, Turkey)

3) Dr. Arif Hussain (UGC Kothari Fellow at Indian Institute of Science, Bangalore)

4) Dr. Ashutosh Kumar  (Asst. Professor, Central University of Tripura, India)

5) Dr. P. Sandhya Rani  (Post-doctoral Fellow at the Indian Institute of Science, Bangalore)

6) Dr. Ramani Baddam (Sr International Fellow, icddr,b; Dhaka)

7) Dr. Narender Kumar (Post-doctoral Fellow, Cambridge University/Wellcome Trust Sanger Institute, Cambridge, UK)

8) Dr. Suma Tiruvayipati (Post-doctoral Fellow, University of Chicago, USA)

9) Dr. Savita Jadhav (Assoc. Professor, Dept. of Microbiology, DY Patil University, Pune, India)

10) Dr. Shaik Sabiha (Consultant, icddr,b; Dhaka)

11) Dr. Sankara Doddam (Post doctoral Fellow, UoH, Hyderabad)

12) Dr. Savita Devi (Post doctoral Fellow, Medical College of Wisconsin, USA)

13) Dr. Amit Ranjan (Post doctoral Fellow, UCONN Health Center, Connecticut, USA)

 

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