|Name:||Dr. Ashutosh Kumar|
|Phone number's :|
|Academic Qualifications :||Postdoctoral Fellow (Indian Institute of Technology Delhi and TIFR-National Centre for Biological Sciences, Bangalore), Ph.D. Biotechnology (University of Hyderabad) , M.Sc. Biotechnology (University of Hyderabad)|
|Present Designation/position :||Assistant Professor|
|Topics Taught :||Molecular Biology and Microbial Genetics, Microbial Biofilms, Biological Methods, Microbial adaptation, Biophysics and Instrumentation, Microbial physiology and metabolism|
Bacterial adaptation mechanisms to stress conditions
Drug tolerance/resistance mechanism
Host pathways modulation by intracellular pathogens
Overlapping host pathways modulated in lysosomal disorders and microbial infections
Dr. Kumar has specialization in the field of cell and molecular biology, microbial pathogenesis and host-pathogen interactions. He has made significant contributions to the study of virulence mechanisms and strategies of survival, adaptation and persistence of Mycobacterium tuberculosis. Mycobacterium tuberculosis can exist in an active form or in a dormant state in lungs after forming granuloma where it can prolong its persistence. To survive under such unfavorable conditions of high nitric oxide, low oxygen and absence of nutrients in the granulomas, M. tuberculosis might have evolved a machinery wherein it decreases growth rate to conserve its cellular resources. Bacteria may regulate their growth for adaptation to stress/dormancy at the level of replication, transcription or/and translation. In every organism, ribosomes play important roles in translation of the genetic information into functional proteins. Much of the cellular energy is directed at ribosome and protein synthesis. The Rv0079 encoded mycobacterial protein is involved with the regulation of translation through its interaction with bacterial ribosomal subunits. The protein appears to arrest protein synthesis as evident from in-silico docking simulation followed by in vitro translation experiments and growth curve analysis involving recombinant E. coli expressing Rv0079. Bacille Calmette Gue´rin (BCG) overexpressing Rv0079 induces secretion of proinflammatory cytokine (IFN-γ, TNF-α, IL- 1β and IL-8) upon infection of macrophages and PBMCs. In-silico analyses pointed to an interaction of Rv0079 with TLR2 and this was confirmed by the observed interaction of recombinant Rv0079 with TLR2 expressedby HEK293 cells. In summary, the interaction with ribosomes are very supportive of the predicted role of Rv0079 protein in translation regulation and the immune functions point to the role of this protein in the maintenance of latency.
Disease relapse occurs due to incomplete clearance of the pathogen and reactivation of the antibiotic tolerant bacilli. M.tb, like other bacterial pathogens, creates an ecosystem of biofilm formed by several proteins including the cyclophilins. Dr. Kumar was involved in identification of an enzyme, PpiB, from M. tuberculosis that promoted biofilm formation and tolerance to anti-mycobacterial drugs. PpiB interacts with several drugs that are currently used to treat diabetes, immunological diseases and cancer. These drugs destabilise M. tuberculosis biofilms in culture and enhanced the potency of two current anti-tuberculosis antibiotics. Comparison of the drugs binding sites in PpiB homologues of other biofilm forming infectious pathogens revealed that these have largely remained unaltered across bacterial species. Targeting bacterial biofilms could be a generic strategy for intervention against bacterial pathogens.
Presently, he works in the area of research such as bacterial adaptation mechanisms to stress conditions, drug tolerance/resistance mechanisms, drug repurposing, host pathways modulation by intracellular pathogens and overlapping host pathways modulated in lysosomal disorders and microbial infections.
27. Borthakur D, Rani M, Das K, Shah MP, Sharma BK, Kumar A. Bioremediation: an alternative approach for detoxification of polymers from the contaminated environment, Letters in Applied Microbiology. (Impact Factor: 2.858)
26. Minocha, S., Khadgawat, P., Bhattacharjee, A., Kumar, A., Tripathi, T., Pandey, S. and Tripathi, D., 2021. Role of Microbial Nanotechnology in Diagnostics. In Microbial Nanotechnology: Green Synthesis and Applications (pp. 237-274). Springer. (Book Chapter).
25. Rani, M., Bhattacharjee, A., Singh, P., Basu, S., Das, K., Goswami, K., Pandey, S., Tripathi, D. and Kumar, A.,. Antimicrobial activities of different nanoparticles concerning to wastewater treatment. In Development in Wastewater Treatment Research and Processes (pp. 501-514). Elsevier. (Book Chapter).
24. Rani, M., Paul, B., Bhattacharjee, A., Das, K., Singh, P., Basu, S., Pandey, S., Tripathi, D. and Kumar, A.,. Detection and removal of pathogenic bacteria from wastewater using various nanoparticles. In Development in Wastewater Treatment Research and Processes (pp. 311-322). Elsevier.(Book Chapter).
23. Shaon Ray Chaudhuri, Basant Kumar Agarwala, Sunil K Sett, Priyasankar Chaudhuri, Piyali Paul, Gourav Bhattacharjee, Sumona Deb, Sukanya Chowdhury, Purnasree Devi, Sinchini Barman, Mandakini Gogoi, Tethi Biswas, Purabi Baidya, Abhispa Bora, Amrita Chakraborty, Chaitali Chanda, Saurav Saha, Ajoy Modak, Gautam Das, Priya Sarkar, Ronald Jamatia, Amitava Mukherjee, Ashutosh Kumar, Ashoke Ranjan Thakur, Mathumal Sudarshan, Rajib Nath, Leena Mishra, Indranil Mukherjee, Gautam Bose, Amarpreet Singh, Ranjan Kumar Naik. 2021. Self-sustained ramie cultivation: an alternative livelihood option. In the book Bioresource Utilization in Therapeutics, Biofuel, Agriculture and Environmental Protection, book edited by Thatoi, Das and Mahapatra. Apple Academic Press (AAP), Inc., Canada, a Taylor & Francis group. (Book Chapter).
22. Pranami Bharadwaj, Deeksha Tripathi, Saurabh Pandey, Sharmistha Tapadar, Arunima Bhattacharjee, Dimpal Das, Espita Palwan, Mamta Rani and Ashutosh Kumar (2021) Molecular biology techniques for the detection of contaminants in wastewater, in the book entitled “Wastewater Treatment: Cutting Edge Molecular Tools, Techniques and Applied Aspects" by Elsevier. ISBN: 9780128218815 (Book Chapter).
21. Sharmistha Tapadar, Deeksha Tripathi, Saurabh Pandey, Khyati Goswami, Arunima Bhattacharjee, Kunwali Das, Espita Palwan, Mamta Rani, and Ashutosh Kumar: Role of Extremophiles and Extremophilic Proteins in Industrial Waste Treatment, in the book entitled " Removal of Emerging Contaminants through Microbial Processes " Springer Nature, ISBN 978-981-15-5900-6, https://doi.org/10.1007/978-981-15-5901-3_11 (Book Chapter)
20. Alam A, Kumar A, Tripathi P, Ehtesham NZ, Hasnain SE (2019) Biofilms: A Phenotypic Mechanism of Bacteria Conferring Tolerance Against Stress and Antibiotics in the book entitled "Mycobacterium tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions" Springer Nature, ISBN 978-981-329-413-4 (Book Chapter)
19. Kumar A, Alam A, Bharadwaj P, Tapadar S, Rani M, Hasnain SE (2019) Toxin-Antitoxin (TA) Systems in Stress Survival and Pathogenesis in the book entitled "Mycobacterium tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions" Springer Nature, ISBN 978-981-329-413-4 (Book Chapter)
18. Kumar A, Alam A, Grover S, Pandey S, Tripathi D, Kumari M, Rani M, Singh A, Akhter Y, Ehtesham NZ, Hasnain SE. (2019) Peptidyl-prolyl isomerase-B is involved in Mycobacterium tuberculosis biofilm formation and a generic target for drug repurposing-based intervention. npj Biofilms and Microbiomes. (Impact Factor = 7.290)
17. Azam M, Jan AT, Kumar A, Siddiqui K, Mondal AH, Haq QMR. Study of pandrug and heavy metal resistance among E. coli from anthropogenically influenced Delhi stretch of river Yamuna. Braz J Microbiol. 2018 Feb 12. pii: S1517-8382(16)30975-3. doi: 10.1016/j.bjm.2017.11.001.(Impact Factor =2.476)
16. Alam A, Kumar A, Kohli S, Singh Y, Sharma K, Ehtesham NZ, Hasnain SE (2018) “Functional Characterization of Mycobacterial Protein PE18/Rv1788 and its ortholog MIP_03868: A comparative study” in Molecular Medicine: Bench to Benchside; Indian Society for the study of Reproduction and Fertility, ISBN: 978-81-936756-0-1, 2018;107-116 (Book Chapter)
15. Kumar A, Alam A, Tripathi D, Rani M, Khatoon H, Pandey S, Ehtesham NZ, Hasnain SE. (2018) Protein adaptations in extremophiles: An insight into extremophilic connection of mycobacterial proteome. Semin Cell Dev Biol. 2018 Jan 16. pii: S1084-9521(17)30144-1. doi: 10.1016/j.semcdb.2018.01.003. (Impact Factor: 7.727)
14. Kumar A, Alam A, Rani M, Ehtesham NZ, Hasnain SE. (2017) Biofilms: survival and defense strategy for pathogens. Int J Med Microbiol. 2017, 307 (8):481-9. (Impact Factor: 3.473)
13. Kumar A, Rani M, Ehtesham NZ, Hasnain SE (2017) Commentary:Modification of host responses by Mycobacteria. Front. Immunol. 8:466. (Impact Factor: 7.561)
12. Pandey S, Tripathi D, Khubaib M, Kumar A, Sheikh JA, Sumanlatha G, Ehtesham NZ, Hasnain SE (2017) Mycobacterium tuberculosis Peptidyl-Prolyl Isomerases Are Immunogenic, Alter Cytokine Proﬁle and Aid in Intracellular Survival. Front. Cell. Infect. Microbiol. 7:38. (Impact Factor: 5.293)
11. Subramaniam M, Lionel LA In, Kumar A, Ahmed N, Nagoor NH: Cytotoxic and apoptotic effects of heat killed Mycobacterium indicus pranii (MIP) on various human cancer cell lines. Scientific Reports. 2016 Jan 28;6:19833. (Impact Factor: 4.379)
10. Pandey S, Sharma A, Tripathi D, Kumar A, Khubaib M, Bhuwan M, Chaudhuri TK, Hasnain SE, Ehtesham NZ: Mycobacterium tuberculosis peptidyl-prolyl isomerases also exhibit chaperone like activity in-vitro and in-vivo. PLoS One. 2016 Mar 16;11(3):e0150288. (Impact Factor: 3.240)
9. Rani PS, Doddam SN, Agrawal S, Hasnain SE, Sechi LA, Kumar A, Ahmed N: Mycobacterium avium subsp. paratuberculosis is not discerned in diabetes mellitus patients in Hyderabad, India. Int J Med Microbiol. 2014 Jul;304(5-6):620-5. (Impact Factor: 3.473)
8. Ansari SA, Devi S, Tenguria S, Kumar A, Ahmed N: Helicobacter pylori protein HP0986 (TieA) interacts with mouse TNFR1 and triggers proin flammatory andproapoptotic signaling pathways in cultured macrophage cells (RAW 264.7). Cytokine. 2014 Aug;68(2):110-7. (Impact Factor: 3.861)
7. Majid M, Kumar N, Qureshi A, Yerra P, Kumar A, Kumar MK, Tiruvayipati S, Baddam R, Shaik S, Srikantam A, Ahmed N: Genomes of Two Clinical Isolates of Mycobacterium tuberculosis from Odisha, India. Genome Announc. 2014 Mar 20;2(2).
6. Kumar A, Lewin A, Rani PS, Qureshi IA, Devi S, Majid M, Kamal E, Marek S, Hasnain SE, Ahmed N.: Dormancy Associated Translation Inhibitor (DATIN) of Mycobacterium tuberculosis interacts with TLR2 and induces proinflammatory cytokine expression. Cytokine. 2013 Oct;64(1):258-64. (Impact Factor: 3.861)
5. Rani PS, Babajan B, Tulsian NK, Begum M, Kumar A, Ahmed N: Mycobacterial Hsp65 potentially cross react with autoantibodies of diabetic sera and also induces (in vitro) cytokine responses relevant to diabetes mellitus. Mol Biosyst. 2013 Nov;9(11):2932-41. (Impact Factor: 3.743)
4. Kumar A, Majid M, Kunisch R, Rani PS, Qureshi IA, Lewin A, Hasnain SE, Ahmed N: Mycobacterium tuberculosis DosR Regulon Gene Rv0079 Encodes a Putative, ‘Dormancy Associated Translation Inhibitor (DATIN)’. PLoS One. 2012;7(6):e38709. (Impact Factor: 3.240)
3. Khattak FA, Kumar A, Kamal E, Kunisch R, Lewin A: Illegitimate recombination: An efficient method for random mutagenesis in Mycobacterium avium subsp. hominissuis. BMC Microbiol. 2012 Sep 11;12:204. (Impact Factor: 3.605)
2. Thomas SK, Iravatham CC, Moni BH, Kumar A, Archana BV, Majid M, Priyadarshini Y, Rani PS, Valluri V, Hasnain SE, Ahmed N: Modern and Ancestral Genotypes of Mycobacetrium tuberculosis from Andhra Pradesh, India. PLoS One. 2011;6(11):e27584. (Impact Factor: 3.240)
1. Jadhav S, Hussain A, Devi S, Kumar A, Parveen S, Gandham N, Wieler LH, Ewers C, Ahmed N: Virulence Characteristics and Genetic Affinities of Multiple Drug Resistant Uropathogenic Escherichia coli from Semi Urban Locality in India. PLoS One. 2011 Mar 25;6(3):e18063. (Impact Factor: 3.240)
Title: “A Medicament For The Treatment Of Diseases By Biofilm Forming Microorganisms”, Pub No: WO/2018/193477, Application No: PCT/IN2018/050238, Publication date: 25.10.2018, International Filing Date: 20.04.2018.
2019: UGC Startup grant -08 Lakh
Vacancies are available in the lab for hosting PhD students through TU RET Exam/JRF/NET and postdoctoral fellows/research associates who are having their own fellowships. Applicants may send: Proposal for Post doc/RA and complete CV to ashu.mtb[at]gmail.com
(1) Sharmistha Tapadar
(2) Purnita Bhattacharyya
Attended Online Coursera Conference 2021: Building a More Just World Together from April 19-21, 2021. The agenda of conference were to teach: How higher education, business, and government institutions are bridging the skill gap, How to leverage the power of the Coursera platform to integrate online learning and improve student employability, How to prepare students and citizens for the economy of tomorrow.
Scientific Reports (a nature reserarch journal), Journal of Biomolecular Structure and Dynamics, BMC Microbiology, BMC Genomics, Molecular Biotechnology, PloS One, Archives of Microbiology, Gut Pathogens, Cogent Biology, Environmental Sustainability, Microbiology and Immunology
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Dr. Kumar was involved in identification and characterization of dormancy associated translation inhibitor (DATIN) of Mycobacterium tuberculosis that inhibit bacterial translation by interacting with ribosome for dormancy survival (Kumar et al., PlosOne, 2012). DATIN is also a potential ligand of TLR2 and contributes to innate responses relevant in the formation and maintenance of tubercular granuloma (Kumar et al., Cytokine, 2013). Disease relapse occurs due to incomplete clearance of the pathogen and reactivation of the antibiotic tolerant bacilli (Kumar et al., Int J Med Microbiol., 2017). He shows that the M.tb cyclophilin peptidyl-prolyl isomerase (PpiB), an essential gene, is involved in biofilm formation and tolerance to anti-mycobacterial drugs. Prediction of interactions between PpiB and US FDA approved drugs (cyclosporine-A and acarbose) and gallium nanoparticle (GaNP) by in-silico docking studies were done and confirmed by surface plasmon resonance (SPR) spectroscopy. Cyclosporine-A and GaNP additionally disrupted M.tb H37Rv biofilm formation. Co-culturing M.tb in their presence resulted in significant decrease in dosage of anti-tubercular drugs- isoniazid and ethambutol. Comparison of the cyclosporine-A and acarbose binding sites in PpiB homologues of other biofilm forming infectious pathogens revealed that these have largely remained unaltered across bacterial species. Targeting bacterial biofilms could be a generic strategy for intervention against bacterial pathogens (Kumar et al., npj Biofilms and Microbiomes, 2019). Analyses of different proteins of M.tb show extremophilic connection of mycobacterial proteome that may be due to intracellular adaptation strategies of M.tb to survive in stresses similar to extremophiles (Kumar et al., Semin Cell Dev Biol., 2018).
Dr Kumar has also contributed in several other important studies.
Peptidyl-prolyl cis-trans isomerases (Ppiases), also known as cyclophilins, are ubiquitously expressed enzymes that assist in protein folding by isomerization of peptide bonds preceding prolyl residues. M.tb is known to possess two Ppiases, PpiA and PpiB. Recombinant PpiA and rPpiB can bind to non-native proteins in vitro and can prevent their aggregation. HEK293T cells transiently expressing M.tb PpiA and PpiB proteins show increased survival in response to oxidative stress and hypoxic conditions generated after treatment with H2O2 and CoCl2 thereby pointing to their likely role in adaption under host generated oxidative stress and conditions of hypoxia (Pandey et al., PLoS One, 2016). ELISA results revealed significant presence of antibodies to M. tb Ppiases in patient sera as compared to sera from healthy individuals. Treatment of THP-1 cells with increasing concentrations of rPpiA, induced secretion of pro-inflammatory cytokines TNF-α and IL-6. Alternatively, treatment with rPpiB inhibited secretion of TNF-α and induced secretion of IL-10. Furthermore, heterologous expression of M. tb PpiA and PpiB in M. smegmatis increased bacterial survival in THP-1 cells (Pandey et al., Front. Cell. Infect. Microbiol., 2017).
Traditionally, the distribution of the M.tb genotypes in India has been characterized by widespread prevalence of ancestral lineages (TbD1+ strains and variants) in the south and the modern forms (TbD1(-) CAS and variants) predominating in the north of India. Spoligotyping of 101 clinical isolates obtained from Hyderabad and rural Andhra Pradesh confirmed the occurrence of major genogroups such as the ancestral, the Central Asian or Delhi type and the Beijing lineage in Andhra Pradesh. It was found that the major genogroups, CAS and "ancestral," were almost equally prevalent in our collection but followed a north-south compartmentalization. However, we observed a significant presence of MANU lineage in south Andhra Pradesh, which was earlier reported to be overwhelmingly present in Mumbai. This study portrays genotypic diversity of M.tb from the Indian state of Andhra Pradesh and provides a much needed snapshot of the strain diversity that will be helpful in devising effective TB control programs in this part of the world (Thomas et al., PLoS One. 2011).
Mycobacterium indicus pranii (MIP) is a non-pathogenic mycobacterium, which has been tested on several cancer types like lung and bladder where tumour regression and complete recovery was observed. In discovering the potential cytotoxic elements, a preliminary test was carried out using four different fractions consisting of live bacteria, culture supernatant, heat killed bacteria and heat killed culture supernatant of MIP against two human cancer cells A549 and CaSki by MTT assay. Apoptosis was investigated in MCF-7 and ORL-115 cancer cells by poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation assays. Among four MIP fractions, only heat killed MIP (HKB) fraction showed significant cytotoxicity in various cancer cells. HKB did not show cytotoxic effects on non-cancerous cells contrary to cancerous cells, suggesting its safe usage and ability to differentially recognize between these cells. Evaluation on PARP assay further suggested that cytotoxicity in cancer cells were potentially induced via caspase-mediated apoptosis (Subramaniam et al., Scientific Reports, 2016).
Mycobacterium avium ssp. paratuberculosis (MAP) is an obligate intracellular pathogen. It causes chronic intestinal inflammation in ruminants known as Johne's disease and is associated with human Crohn's disease. Furthermore, association of MAP with other autoimmune diseases, such as type-1 diabetes, has been established in patients from Sardinia (Italy) which is a MAP endemic and genetically isolated region. Due to largest livestock population and consequently high MAP prevalence amidst a very high diabetes incidence in India, we sought to test this association on a limited number of patient samples from Hyderabad. Our results of ELISA with MAP lysate and MAP-specific protein MAP3738c as well as PCR/real-time PCR of MAP-specific sequences IS900 and/or f57 indicated that, in contrast to Sardinian diabetic patients, MAP infection in blood is not discerned in diabetic patients in Hyderabad. The association of a mycobacterial trigger with diabetes therefore could well be a population-specific phenomenon, highly dependent on genetic repertoire and the environment of susceptible populations (Rani et al., Int J Med Microbiol., 2014).
Diabetes mellitus is a multifactorial disease and its incidence is increasing worldwide. Among the two types of diabetes, type-2 accounts for about 90% of all diabetic cases, whereas type-1 or juvenile diabetes is less prevalent and presents with humoral immune responses against some of the autoantigens. We attempted to test whether the sera of type-1 diabetes patients cross-react with mycobacterial heat shock protein 65 (Hsp65) due to postulated epitope homologies between mycobacterial Hsp65 and an important autoantigen of type-1 diabetes, glutamic acid decarboxylase-65 (GAD65). The indirect ELISA results indicated that both type-1 diabetes and type-2 diabetes sera cross-react with conserved mycobacterial Hsp65 peptides and recombinant mycobacterial Hsp65 protein. Our results suggest that cross-reactivity of mycobacterial Hsp65 with autoantibodies of diabetes sera could be due to the presence of significantly conserved peptides between mycobacterial Hsp65 and human Hsp60 rather than between mycobacterial Hsp65 and GAD65. The treatment of human peripheral blood mononuclear cells (PBMCs) with recombinant mycobacterial Hsp65 protein or the synthetic peptides resulted in a significant increase in the secretion of cytokines such as IL-1β, IL-8, IL-6, TNF-α and IL-10. These findings point towards a dual role for mycobacterial Hsp65: in inducing autoimmunity and in inflammation, the two cardinal features of diabetes mellitus (Rani et al., Mol Biosyst. 2013).
Extraintestinal pathogenic E. coli (ExPEC) are of significant health concern. The emergence of drug resistant E. coli with high virulence potential is alarming. Lack of sufficient data on transmission dynamics, virulence spectrum and antimicrobial resistance of certain pathogens such as the uropathogenic E. coli (UPEC) from countries with high infection burden, such as India, hinders the infection control and management efforts. Extensive genotype and phenotype study of a collection of 150 UPEC obtained from patients belonging to a semi-urban, industrialized setting near Pune, India. The isolates representing different clinical categories were analyzed in comparison with 50 commensal E. coli isolates from India as well as 50 ExPEC strains from Germany. Virulent strains were identified based on hemolysis, haemagglutination, cell surface hydrophobicity, serum bactericidal activity as well as with the help of O serotyping. We generated antimicrobial resistance profiles for all the clinical isolates and carried out phylogenetic analysis based on repetitive extragenic palindromic (rep)-PCR. E. coli from urinary tract infection cases expressed higher percentages of type I (45%) and P fimbriae (40%) when compared to fecal isolates (25% and 8% respectively). Hemolytic group comprised of 60% of UPEC and only 2% of E. coli from feces. Moreover, clinical isolates exhibited highest resistance against amoxicillin (67.3%) and least against nitrofurantoin (57.3%). We also observed that 31.3% of UPEC were extended-spectrum beta-lactamase (ESBL) producers belonging to serotype O25, of which four were also positive for O25b subgroup that is linked to B2-O25b-ST131-CTX-M-15 virulent/multiresistant type. Furthermore, isolates from India and Germany (as well as global sources) were found to be genetically distinct with no evidence to espouse expansion of E. coli from India to the west or vice-versa (Jadhav et al., PLoS One. 2011).
Escalating burden of antibiotic resistance that has reached new heights present a grave concern to mankind. As the problem is no longer confined to clinics, identification of a pandrug resistant E. coli isolate from heavily polluted Delhi stretch of river Yamuna, India was done. E. coli MRC11 was found sensitive only to tobramycin against 21 antibiotics tested, with minimum inhibitory concentration values >256μg/mL for amoxicillin, carbenicillin, aztreonam, ceftazidime and cefotaxime. Addition of certain heavy metals at higher concentrations were ineffective in increasing susceptibility of E. coli MRC11 to antibiotics. Withstanding sub-optimal concentration of cefotaxime (10μg/mL) and mercuric chloride (2μg/mL), and also resistance to their combinatorial use, indicates better adaptability in heavily polluted environment through clustering and expression of resistance genes (Azam et al., Braz J Microbiol. 2018).
H. pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. HP0986 protein of H. pylori has been shown to trigger induction of proinflammatory cytokines (IL-8 and TNF-α) through the activation of NF-κB and also to induce Fas mediated apoptosis of human macrophage cells (THP-1). Our studies indicated activation of TNFR1 through interaction with HP0986 and this elicited the aforementioned responses independent of TLR2, TLR4 or TNFR2. We found that mouse TNFR1 activation by HP0986 facilitates formation of a complex comprising of TNFR1, TRADD and TRAF2, and this occurs upstream of NF-κB activation. Furthermore, FADD also forms a second complex, at a later stage, together with TNFR1 and TRADD, resulting in caspase-8 activation and thereby the apoptosis of RAW 264.7 cellsThese observations form much needed baseline data entailing future in vivo studies of the functions of HP0986 in a murine model (Ansari et al., Cytokine, 2014).
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