Qualification: 
Ph.D
Email: 
sujayc@am.amrita.edu
Phone: 
+91 0476-280-3122

Dr. Sujay Chattopadhyay received his MTech in Biotechnology from Indian Institute of Technology, Kharagpur, India. He completed his PhD in Bioinformatics and Computational Biology from the Department of Theoretical Physics at Indian Association for the Cultivation of Science, Kolkata, India. He pursued his post-doctoral research in Department of Microbiology, University of Washington, Seattle, USA. In UW Microbiology, he later continued to work as an Acting Instructor followed by Research Assistant Professor. In USA, he performed computational biology research in the field of microbial evolution, primarily in E. coli and Samonella. Using these species as case studies, he developed multiple analytical tools and database:

(a) ‘Zonal Phylogeny Software’ and ‘TimeZone’ for gene-based and genome-wide mapping of adaptive mutational footprints;

(b) ‘PanCoreGen’ for profiling, detecting and annotating protein-coding genes in microbial genomes;

(c) Prototype microbial variome databases using E. coli and Salmonella.

He has also been a consultant for a Seattle, USA based molecular diagnostic start-up ID Genomics, for which he received a US patent (# 15/055,376 filed on February 26,2016) titled ‘Process and Kit for Predicting Antibiotic Resistance and Susceptibility of Bacteria’ for detecting high-resolution genotyping markers to aid clonal diagnostics.

Dr. Chattopadhyay is an Associate Professor at Amrita School of Biotechnology and his current research focuses on:

  1. Adaptive Co-evolution of Genes in Microbial Pathogens.

    Similar to genome-wide association studies in humans, given a large sample size, the co-evolved loci or adaptive mutations in microbes (pathogens in particular) can in effect be predicted for their association to specific host-compartments, geographical locations, epidemic/endemic outbreaks, or disease phenotypes in hosts. The present pace of genome sequencing indicates that, by using affordable and rapid sequencing technologies, tens of thousands of microbial genomes will be sequenced during this decade, thereby enabling us perform such association studies in near future. This project plans to develop an analytical tool to detect co-evolution of genes across the genome, to be used to assess phylogenetic congruence for the entire tree (i.e. involving all isolates) or for any sub-tree (i.e. across specific phylogenetic clades) for a given species. This information will provide important insights to create genomic network of adaptive loci functioning within a particular bacterial lineage or across multiple lineages in parallel.

    An important extension of within-species co-evolution studies would be to study cross-species interplay of such adaptive forces in a given habitat. His earlier work on Escherichia coli and Salmonella enterica subspecies I core genes demonstrated that there was a significant overlap in the functional trajectories of adaptive evolution in two species. Recent studies showed that specific virulence factors in S. typhimurium stimulate strong host inflammatory response, and eventually help the pathogen gain an advantage in its growth competition with the resident microbiota. Therefore, it would be important to study the role of co-evolving metabolic pathways in the interactions/competitions of microbiota in host-compartments, e.g. in the inflamed gut. Such a study can offer the possibility to identify new targets for intervention.

  2. Role of Truncation Mutations in Virulence Evolution.

    Occurrence of pseudogene formation via truncation mutation and gene deletion is a common phenomenon in bacterial world, especially in the evolution of the host-adapted/host-restricted bacterial pathogens. A general belief is that pseudogene formation and gene deletion are results of reductive evolution, following a ‘use-or-lose’ dynamics which suggests purging of traits that are of no use in the organism. Based on the preliminary studies on Salmonella, however, Dr. Chattopadhyay’s lab hypothesizes that accumulation of truncation mutations leading to pseudogene formation can often be result of adaptive evolution. We anticipate that such events rather follow a ‘die-or-lose’ dynamics indicating purging of traits that are otherwise deleterious to the organism.

    The goal of this project is to understand the role of gene inactivation via truncation mutations in the (patho)adaptive evolution of bacteria. Events leading to evolutionary convergence are often adaptive and positively selected. Based on the detection of recent non-random convergent events of truncation mutations, the lab proposes a novel approach to distinguish adaptive truncation mutations from reductive ones. The primary focus in this study will be on Salmonella, along with other pathogens, for developing the analytical tool to decipher the adaptive significance of gene truncation mutations leading to the loss of protein function.

  3. Clonal Evolution of Virulence and Antibiotic Resistance.

    Most bacterial species, pathogens or commensals, are clonal in nature, represented by the strains with distinct phenotypes circulating as a limited number of genetically related (i.e. clonal) lineages. The stability of such (adapted) clonal lineages has been demonstrated to be strong enough, both temporally and spatially, to decipher consistent clonal association with important traits like specific virulence potentials or antibiotic resistance profiles.

    Multilocus sequence typing (MLST) is presently the method of choice for determining the clonal structure of a bacterial species, and for numerous important pathogens the MLST schemes have been standardized. However, since the STs are discriminated based on the genetic relatedness of a set of housekeeping genes, they are neither uniform nor fine-tuned with respect to the pathotypes and resistance/susceptibility profiles of their representative strains. For example, in E. coli, ST73 includes pathogenic strains like CFT073 that causes pyelonephritis in humans, as well as commensal strains like ABU83972 and Nissle1917 that have been used as probiotics in humans. Also, MLST requires involvement of 7 loci, limiting its efficiency in terms cost and time. This work aims to detect potential candidate genes and mutations therein as high-resolution clonal markers for selected bacterial pathogens to associate specific virulence and/or multidrug resistance properties of interest.

Publications

Publication Type: Journal Article

Year of Publication Publication Type Title

2016

Journal Article

S. Paul, E. V. Sokurenko, and S. Chattopadhyay, “Corrected Genome Annotations Reveal Gene Loss and Antibiotic Resistance as Drivers in the Fitness Evolution of Salmonella Enterica Serovar Typhimurium”, Journal of Bacteriology, vol. 198, pp. 3152-3161, 2016.[Abstract]


Horizontal acquisition of novel chromosomal genes is considered to be a key process in the evolution of bacterial pathogens. However, the identification of gene presence or absence could be hindered by the inconsistencies in bacterial genome annotations. Here, we performed a cross-annotation of omnipresent core and mosaic accessory genes in the chromosome of Salmonella enterica serovar Typhimurium across a total of 20 fully assembled genomes deposited into GenBank. Cross-annotation resulted in a 32% increase in the number of core genes and a 3-fold decrease in the number of genes identified as mosaic genes (i.e., genes present in some strains only) by the original annotation. Of the remaining noncore genes, the vast majority were prophage genes, and 255 of the nonphage genes were actually of core origin but lost in some strains upon the emergence of the S. Typhimurium serovar, suggesting that the chromosomal portion of the S. Typhimurium genome acquired a very limited number of novel genes other than prophages. Only horizontally acquired nonphage genes related to bacterial fitness or virulence were found in four recently sequenced isolates, all located on three different genomic islands that harbor multidrug resistance determinants. Thus, the extensive use of antimicrobials could be the main selection force behind the new fitness gene acquisition and the emergence of novel Salmonella pathotypes.

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2016

Journal Article

S. Paul, M. F. Minnick, and S. Chattopadhyay, “Mutation-Driven Divergence and Convergence Indicate Adaptive Evolution of the Intracellular Human-Restricted Pathogen, Bartonella bacilliformis”, PLOS Neglected Tropical Diseases, vol. 10, pp. 1-17, 2016.[Abstract]


Author Summary How host-restriction, intracellularity and genome reduction interplay to exert or maintain virulence is poorly characterized. The fact that B. bacilliformis is the most pathogenic Bartonella and has a highly reduced genome makes it an attractive model to gain insights into (patho)adaptive evolution of intracellular pathogens. Also, B. bacilliformis is known to lack many virulence genes present in other Bartonella, indicating unique strategies of (patho)adaptation. Our study reveals a prevalent nature of mutational force in B. bacilliformis evolution with two distinct outcomes: (a) mutational divergence leading to sub-speciation, possibly recently, via accelerated accumulation and fixation of favorable mutations mediated by a mutator phenotype; and (b) mutational convergence between clones of a sub-species exhibiting shared functional trajectories of adaptive evolution. Our findings highlight positions accumulating adaptive mutations in candidate genes, offering future functional studies to elucidate B. bacilliformis virulence evolution, and of broad application to intracellular pathogens with a reduced gene repertoire.

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2015

Journal Article

S. Paul, A. Bhardwaj, S. K. Bag, E. V. Sokurenko, and S. Chattopadhyay, “PanCoreGen — Profiling, Detecting, Annotating Protein-coding Genes in Microbial Genomes”, Genomics, vol. 106, pp. 367 - 372, 2015.[Abstract]


A large amount of genomic data, especially from multiple isolates of a single species, has opened new vistas for microbial genomics analysis. Analyzing the pan-genome (i.e. the sum of genetic repertoire) of microbial species is crucial in understanding the dynamics of molecular evolution, where virulence evolution is of major interest. Here we present PanCoreGen — a standalone application for pan- and core-genomic profiling of microbial protein-coding genes. PanCoreGen overcomes key limitations of the existing pan-genomic analysis tools, and develops an integrated annotation-structure for a species-specific pan-genomic profile. It provides important new features for annotating draft genomes/contigs and detecting unidentified genes in annotated genomes. It also generates user-defined group-specific datasets within the pan-genome. Interestingly, analyzing an example-set of Salmonella genomes, we detect potential footprints of adaptive convergence of horizontally transferred genes in two human-restricted pathogenic serovars — Typhi and Paratyphi A. Overall, PanCoreGen represents a state-of-the-art tool for microbial phylogenomics and pathogenomics study

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2013

Journal Article

S. Chattopadhyay, F. Taub, S. Paul, and E. V. Sokurenko, “Microbial Variome Database: Point Mutations, Adaptive or Not, in Bacterial Core Genomes”, Molecular Biology and Evolution, vol. 30, pp. 1465-1470, 2013.[Abstract]


Analysis of genetic differences (gene presence/absence and nucleotide polymorphisms) among strains of a bacterial species is crucial to understanding molecular mechanisms of bacterial pathogenesis and selecting targets for novel antibacterial therapeutics. However, lack of genome-wide association studies on large and epidemiologically well-defined strain collections from the same species makes it difficult to identify the genes under positive selection and define adaptive polymorphisms in those genes. To address this need and to overcome existing limitations, we propose to create a “microbial variome"—a species-specific resource database of genomic variations based on molecular evolutionary analysis. Here, we present prototype variome databases of&nbsp;<em>Escherichia coli</em>&nbsp;and&nbsp;<em>Salmonella enterica</em>&nbsp;subspecies&nbsp;<em>enterica</em>(<a href="http://depts.washington.edu/sokurel/variome" target="">http://depts.washington.edu/sokurel/variome</a>, last accessed March 26, 2013). The prototypes currently include the point mutations data of core protein-coding genes from completely sequenced genomes of 22&nbsp;<em>E. coli</em>&nbsp;and 17&nbsp;<em>S. enterica</em>strains. These publicly available databases allow for single- and multiple-field sorting, filtering, and searching of the gene variability data and the potential adaptive significance. Such resource databases would immensely help experimental research, clinical diagnostics, epidemiology, and environmental control of human pathogens.

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2013

Journal Article

S. Paul, Million-Weaver, S., S. Chattopadhyay, E. V. Sokurenko, and Merrikh, H., “Replication-Transcription Conflicts Increase the Rate of Evolution in Specific Genes”, Nature, vol. 495, pp. 512-515., 2013.

2013

Journal Article

S. Chattopadhyay, S. Paul, D. E. Dykhuizen, and E. V. Sokurenko, “Tracking Recent Adaptive Evolution in Microbial Species Using TimeZone”, Nature Protocols, vol. 8, 2013.[Abstract]


An important goal of the analysis of sequenced genomes of microbial pathogens is to improve the therapy of infectious diseases. In this context, a major challenge is to detect genomic-level evolutionary changes that increase microbial virulence. TimeZone, a genome analysis software package, is designed to detect footprints of positive selection for functionally adaptive point mutations. The uniqueness of TimeZone lies in its ability to predict recent adaptive mutations that are overlooked by conventional microevolutionary tools. This protocol describes the use of TimeZone to analyze adaptive footprints in either individual genes or in sets of genomes. Three major workflows are described: (i) extraction of orthologous gene sets from multiple genomes; (ii) alignment and phylogenetic analysis of genes; and (iii) identification of candidate genes under positive selection for point mutations, taking into account the effect of recombination events. This software package can be downloaded free from http://sourceforge.net/projects/timezone1/. In the case, for example, of the analysis of 14 Escherichia coli genomes, the protocol described here can be completed in ∼32 h.

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2013

Journal Article

S. Chattopadhyay and E. V. Sokurenko, “Evolution of Pathogenic E. coli. In “Escherichia coli: Pathogenesis and Pathotypes”, In “Escherichia coli: Pathogenesis and Pathotypes”, 2nd edition, 2013.

2012

Journal Article

S. Chattopadhyay, S. Paul, Kisiela, D. I., Linardopoulou, E., and E. V. Sokurenko, “Convergent Molecular Evolution of Genomic Cores in Salmonella Enterica and Escherichia coli.”, Journal of Bacteriology, vol. 194, pp. 5002-5011, 2012.[Abstract]


One of the strongest signals of adaptive molecular evolution of proteins is the occurrence of convergent hot spot mutations: repeated changes in the same amino acid positions. We performed a comparative genome-wide analysis of mutation-driven evolution of core (omnipresent) genes in 17 strains of Salmonella enterica subspecies I and 22 strains of Escherichia coli. More than 20% of core genes in both Salmonella and E. coli accumulated hot spot mutations, with a predominance of identical changes having recent evolutionary origin. There is a significant overlap in the functional categories of the adaptively evolving genes in both species, although mostly via separate molecular mechanisms. As a strong evidence of the link between adaptive mutations and virulence in Salmonella, two human-restricted serovars, Typhi and Paratyphi A, shared the highest number of genes with serovar-specific hot spot mutations. Many of the core genes affected by Typhi/Paratyphi A-specific mutations have known virulence functions. For each species, a list of nonrecombinant core genes (and the hot spot mutations therein) under positive selection is provided.

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2012

Journal Article

D. I. Kisiela, S. Chattopadhyay, Libby, S. J., Tchesnokova, V., Kramer, J. J., Wheeler, E., Mackie, R. I., Clegg, S., and E. V. Sokurenko, “Convergent Evolution of Invasive Serovars of Salmonella Enterica via Point Mutations in the Type 1 Fimbrial Adhesion FimH”, PLoS Pathogens, 2012.

2012

Journal Article

S. Chattopadhyay, Tchesnokova, V., McVeigh, A., Kisiela, D. I., Dori, K., Navarro, A., E. V. Sokurenko, and Savarino, S. J., “Adaptive evolution of class 5 fimbrial genes in enterotoxigenic Escherichia coli and its functional consequences”, Journal of Biological Chemistry, vol. 287, pp. 6150-6158, 2012.[Abstract]


Class 5 fimbriae of enterotoxigenic Escherichia coli (ETEC) comprise eight serologically discrete colonization factors that mediate small intestinal adhesion. Their differentiation has been attributed to the pressure imposed by host adaptive immunity. We sequenced the major pilin and minor adhesin subunit genes of a geographically diverse population of ETEC elaborating CFA/I (n = 31), CS17 (n = 20), and CS2 (n = 18) and elucidated the functional effect of microevolutionary processes. Between the fimbrial types, the pairwise nucleotide diversity for the pilin or adhesin genes ranged from 35–43%. Within each fimbrial type, there were 17 non-synonymous and 1 synonymous point mutations among all pilin or adhesin gene copies, implying that each fimbrial type was acquired by ETEC strains very recently, consistent with a recent origin of this E. coli pathotype. The 17 non-synonymous allelic differences occurred in the CFA/I pilin gene cfaB (two changes) and adhesin gene cfaE (three changes), and CS17 adhesin gene csbD (12 changes). All but one amino acid change in the adhesins clustered around the predicted ligand-binding pocket. Functionally, these changes conferred an increase in cell adhesion in a flow chamber assay. In contrast, the two mutations in the non-adhesive CfaB subunit localized to the intersubunit interface and significantly reduced fimbrial adhesion in this assay. In conclusion, naturally occurring mutations in the ETEC adhesive and non-adhesive subunits altered function, were acquired under positive selection, and are predicted to impact bacteria-host interactions.

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Complete list of Sujay’s publications in peer-reviewed journals

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