Subramony Mahadevan, Ph.D., Professor
The primary focus of our research has been to understand the different survival strategies adopted by microorganisms in their natural habitats. In this context, the evolutionary significance of bacteria maintaining a set of genes that are apparently silent and uninducible has been examined using the beta-glucoside utilization (bgl) genes of Escherichia coli and related microorganisms as an experimental paradigm. These studies have shown that the global regulators, DNA Gyrase, H-NS, CRP-cAMP and RpoS are involved in their regulation, suggesting that conditions that alter these factors may result in transient expression of the bgl genes. Recent investigations have focused on the possible role of the bgl genes in stationary phase. These studies have shown that mutations that activate the bgl genes confer a Growth Advantage in Stationary Phase (GASP) phenotype to the cell and accumulate in bacterial cultures subjected to prolonged starvation. We have recently demonstrated the involvement of the bgl operon in the regulation of an oligopeptide transporter oppA that allows the import of short peptides that can be used both as energy source as well as precursors. Thus, modulation of the activity of genes that are maintained in a silent state offers a powerful mechanism for enhancing the metabolic capability of organisms under stress.
The evolution of new metabolic functions by mutations in preexisting genetic systems has also been investigated with the chb genes of E. coli as a paradigm. Wild type E. coli is not capable of degrading the cellulose-derived disaccharide cellobiose. However, mutations within the chb locus encoding the functions necessary for the catabolism of chitin-derived oligosaccharides can enable the bacterium to acquire the ability to degrade cellobiose. These consist of tandem mutations: mutations that abolish repression by the negative regulator NagC and mutations within the transcriptional regulator chbR that has dual regulatory role as a repressor/activator. Molecular analyses have shown that these mutations result in enhanced DNA binding and effector recognition by ChbR. The acquisition of the cellobiose positive phenotype by wild type strains by mutation is essentially by altering the regulation of the chb genes. Recent observations have also established that the chbG gene that is conserved across phyla encodes a chito-oligosaccharide mono-deacetylase whose activity is essential for induction of the operon as well as the hydrolysis of chito-oligosaccharides. This result has significance beyond the bacterial system as its homologues in vertebrates and humans have been implicated in development and inflammatory bowel disorders respectively.
The ability to hydrolyze aromatic beta-glucosides has been recently correlated with the capacity to avoid predation in the soil environment. The aglycones released during the hydrolysis are toxic to predators, conferring a chemical weapon against predators. Therefore, relief from predation in addition to the generation of metabolic energy provides a strong selective force for the retention of the bgl genes in the genome. These studies have integrated genetic, molecular and behavioural approaches to understand microbial physiology, ecology, and evolution.
Present graduate students:
1. Asha Mary Joseph
2. Shambhavi Shukla
3. Kartika Vashishtha
4. Krithi Nandimath
1. Transcriptional activation of the bgl operon of Escherichia coli: negative regulation by DNA structural elements near the promoter. J. Singh, M. Mukerji and S. Mahadevan Mol. Microbiol. 17: 1085‑1092, 1995.
2. Characterization of the regulatory elements involved in silencing the bgl operon of E. coli: possible roles for DNA gyrase, H‑NS, and CRP‑cAMP in regulation Mukerji, M, and S. Mahadevan. Mol. Microbiol. 24:617-627, 1997.
3. Mechanism of catabolite repression in the bgl operon of Escherichia coli: involvement of the antiterminator BglG, CRP-cAMP and EIIGlc in mediating glucose effect downstream of transcription initiation. Gulati A. and S. Mahadevan. Genes to Cells 5: 239-250, 2000.
4. Analysis of beta-glucoside utilization (bgl) genes in Shigella sonnei: evolutionary implications for their maintenance in a cryptic state. Kharat, A.S. and S. Mahadevan Microbiology 146: 2039-2049, 2000.
5. Differential spectrum of mutations that activate the Escherichia coli bgl operon in an rpoS genetic background. Moorthy, S. and S. Mahadevan J. Bacteriol. 184: 4033-4038, 2002.
6. The beta-glucoside genes of Klebsiella aerogenes: conservation and divergence in relation to the cryptic bgl genes of Escherichia coli. T.R. Raghunand and S. Mahadevan. FEMS Microbiol. Lett. 223: 267-274, 2003
7. Mutations that activate the silent bgl operon of Escherichia coli confer a growth advantage in stationary phase. R. Madan, R. Kolter and S. Mahadevan. J. Bacteriol. 187: 7912-7917, 2005.
8. Mutations that alter the regulation of the chb operon of Escherichia coli allow utilization of cellobiose. Kachroo, A.H., A.K. Kancherla, N.S. Singh, U. Varshney and S. Mahadevan. Mol. Microbiol. 66: 1383-1395, 2007.
9. The β-glucoside (bgl) operon of Escherichia coli is involved in the regulation of oppA encoding an oligo-peptide transporter. Harwani, D. P. Zangoui, and S. Mahadevan. J. Bacteriol 194: 90-99, 2012.
10. The chbG gene of the chitobiose (chb) operon of Escherichia coli encodes a chitoologosaccharide deacetylase . Verma, S. C. and S. Mahadevan. J. Bacteriol. 194: 4959-4971, 2012
11. Involvement of the global regulator H-NS in the survival of Escherichia coli in stationary phase. Chib, S. and S. Mahadevan. J. Bacteriol. 194: 5285-5293, 2012.
12. Hydrolysis of aromatic β-glucosides by non-pathogenic bacteria confers a chemical weapon against predators. Robert Sonowal, Krithi Nandimath, Sucheta S. Kulkarni, Sandhya P. Koushika, Vidyanand Nanjundiah, and S. Mahadevan. Proceed. Royal Soc. B. 280: 20130721, 2013
13. Evolution of aromatic β-glucoside utilization by successive mutational steps in Escherichia coli. Parisa Zangoui, Kartika Vashishtha, and S. Mahadevan. J. Bacteriol. 197(4): 710-716, 2015