Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Functional Annotation of Pathogenesis Proteins in Shigella flexneri using Comparative Genomics


Affiliations
1 Department of Zoology, Government General Degree College, Singur, West Bengal, India
2 Department of Biotechnology, St. Xavier’s College, Kolkata- 700016, India
     

   Subscribe/Renew Journal


The Gram-negative bacteria, Shigella species, is a predominant diarrheal pathogen and itself accounts for 15% of the diarrheal episodes occurring globally. Shigella enters the human body through ingestion of contaminated food and water and on reaching the intestine, dismantles the epithelial barrier, generating symptoms varying from mild to severe bloody diarrhea. Widespread diversity of Shigella species and the emergence of multi-drug resistant strains in recent years has made it extremely enigmatic to design a successful drug to combat shigellosis. This work focusses on comparative genomics methods to identify and annotate hypothetical proteins from the Shigella flexneri genome in quest of identifying novel druggable targets.

Keywords

Shigellosis, Hypothetical Proteins, Comparative Genomics, Drug Targets.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Armitano, J., Redder, P., Guimarães, V. A., Linder, P. 2016. An essential factor for high Mg2+ tolerance of Staphylococcus aureus. Front. Microbiol., 7: 1888.
  • Bondarczuk, K. and Piotrowska-Seget, Z. 2013. Molecular basis of active copper resistance mechanisms in Gram-negative bacteria. Cell Biol. Toxicol., 29(6): 397-405.
  • Chakrabarti, S. and Ganguli, S., 2013. Structural analysis of Shigella invasion proteins reveals non-conserved intrinsically unstructured regions. Int. Lett. Nat. Sci., 5: 52-58.
  • Chen, Y. C., Li, C. L., Hsiao, Y. Y., Duh, Y., Yuan, H. S. 2014. Structure and function of TatD exonuclease in DNA repair. Nucleic Acids Res., 42(16): 10776-10785.
  • Christensen, O., Harvat, E. M., Thöny-Meyer, L., Ferguson, S. J., Stevens, J. M. 2007. loss of ATP hydrolysis activity by CcmAB results in loss of c-type cytochrome synthesis and incomplete processing of CcmE. FEBS J. 274(9): 2322-2332.
  • Cianciotto, N. P., Cornelis, P. and Baysse, C. 2005. Impact of the bacterial type I cytochrome c maturation system on different biological processes. Mol. Microbiol., 56(6): 1408-1415.
  • Cox, M. M. 2003. The bacterial RecA protein as a motor protein. Annu. Rev. Microbiol., 57: 551-577.
  • Deutscher, J., Aké, F. M. D., Derkaoui, M., Zébré, A. C., Cao, T. N., Bouraoui, H., Kentache, T., Mokhtari, A., Milohanic, E. and Joyet, P. 2014. The bacterial phosphoenolpyruvate: carbohydrate phosphotransferase system: regulation by protein phosphorylation and phosphorylation-dependent protein-protein interactions. Microbiol. Mol. Biol. Rev., 78(2): 231-256.
  • Dunwell, J. M., Khuri, S. and Gane, P. J. 2000. Microbial relatives of the seed storage proteins of higher plants: conservation of structure and diversification of function during evolution of the cupin superfamily. Microbiol. Mol. Biol. Rev., 64(1): 153-179.
  • DuPont , H. L., Levine, M. M., Hornick, R. B. and Formal, S. B. 1989. Inoculum size in Shigellosis and implications for expected mode of transmission. J. Infect. Dis., 159(6): 1126-8.
  • Epshtein, V. 2015. UvrD helicase: an old dog with a new trick: how one step backward leads to many steps forward. Bioessays., 37(1): 12-19.
  • Feissner, R. E., Richard-Fogal, C. L., Frawley, E. R. and Kranz, R. G. 2006. ABC transporter-mediated release of a haem chaperone allows cytochrome c biogenesis. Mol. Microbiol., 61(1): 219-231.
  • Finn, R. D., Attwood, T. K., Babbitt and P. C., et al., 2017. Inter pro in 2017-beyond protein family and domain annotations. Nucleic. Acids. Res., 45(D1): D190-D199.
  • Forouhar, F., Hussain, M., Farid, R., Benach, J., Abashidze, M., Edstrom, W. C., Vorobiev, S. M., Xiao, R., Acton, T. B., Fu, Z., Kim, J-J. P., Miziorko, H. M., Montelione, G. T. and Hunt, J. F. 2006. Crystal structures of two bacterial 3-hydroxy-3-methylglutaryl-CoA lyases suggest a common catalytic mechanism among a family of TIM barrel metalloenzymes cleaving carbon-carbon bonds. J. Biol. Chem. 281(11): 7533-7545.
  • Franceschini, A., Szklarczyk, D., Frankild, S., et al., 2013. STRING v9.1: proteinprotein interaction networks, with increased coverage and integration. Nucleic. Acids. Res., 41(Database issue): D808-D815.
  • Gagarinova, A., Stewart, G., Samanfar, B., Phanse, S., White, C. A., Aoki, H., Deineko, V., Beloglazova, N., Yakunin, A. F., Golshani, A., Brown, E. D., Babu, M. and Emili, A. 2016. Systematic genetic screens reveal the dynamic global functional organization of the bacterial translation machinery. Cell Rep., 17(3): 904-916.
  • Gibson, M. M., Bagga, D. A., Miller, C. G. and Maguire, M. E. 1991. Magnesium transport in Salmonella typhimurium: the influence of new mutations conferring Co2+ resistance on the CorA Mg2+ transport system. Mol. Microbiol., 5(11): 2753-2762.
  • Gorden, J. and Small, P. L. 1993. Acid resistance in enteric bacteria. Infect. Immun., 61(1): 364-367.
  • Groicher, K. H., Firek, B. A., Fujimoto, D. F. and Bayles, K. W. 2000. The Staphylococcus aureus lrg AB operon modulates murein hydrolase activity and penicillin tolerance. J. Bacteriol., 182(7): 1794-1801.
  • Haft, D. H., Pierce, P. G., Mayclin, S. J., Sullivan, A., Gardberg, A. S., Abendroth, J., Begley, D. W., Phan, I. Q., Staker, B. L., Myler, P. J., Marathias, V. M., Lorimer, D. D. and Edwards, T. E. 2017. Mycofactocin-associated mycobacterial dehydrogenases with non-exchangeable NAD cofactors. Sci. Rep., 7: 41074.
  • Hale, T. L. and Keusch, G. T. 1996. Shigella. Medical Microbiology. 4th edition.Chapter 22.
  • Hunnicutt, D. W. and McBride, M. J. 2001. Cloning and characterization of the Flavobacterium johnsoniae gliding motility genes gldD and gldE. J. Bacteriol., 183(14): 4167-4175.
  • Ito, T., Iimori, J., Takayama, S., Moriyama, A., Yamauchi, A., Hemmi, H. and Yoshimura, T. 2013. Conserved pyridoxal protein that regulates Ile and Val metabolism. J. Bacteriol., 195(24): 5439-5449.
  • Jin , Q., Yuan, Z., Xu, J., Wang, Y., Shen, Y., Lu, W., Wang, J., Liu, H., Yang, J., Yang, F., Zhang, X., Zhang, J., Yang, G., Wu, H., Qu, D., Dong, J., Sun, L., Xue, Y., Zhao, A., Gao, Y., Zhu, Kan, B., Ding, K., Chen, S., Cheng, H., Yao, Z., He, B., Chen, R., Ma, D., Qiang, B., Wen, Y., Hou, Y. and Yu, J. 2002. Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia Coli K12 and O157. Nucleic Acids Res., 30(20): 4432-4441.
  • Johnson , M., Zaretskaya, I., Raytselis, Y., Merezhuk, Y., McGinnis, S. and Madden, T. L. 2008. NCBI BLAST: a Better web interface. Nucleic Acids Res., 36(Web Server issue) : W6-W9.
  • Kaznadzey, A., Shelyakin, P., Belousova, E., Eremina, A., Shvyreva, U., Bykova, D., Emelianenko, V., Korosteleva, A., Tutukina, M. and Gelfand, M. S. 2018. The genes of the sulphoquinovose catabolism in Escherichia coli are also associated with a previously unknown pathway of lactose degradation. Sci. Rep., 8(1): 3177.
  • Kim, C., Lorenz, W. W., Hoopes, J. T. and Dean, J. F. 2001. Oxidation of phenolate siderophores by the multicopper oxidase encoded by the Escherichia coli yacK gene. J. Bacteriol., 183(16): 4866-4875.
  • Kim, Y., Maltseva, N., Dementieva, I., Collart, F., Holzle, D. and Joachimiak, A. 2006. Crystal structure of hypothetical protein YfiH from Shigella flexneri at 2 A resolution. Proteins., 63(4): 1097-1101.
  • Kingston, A. W., Ponkratz, C. and Raleigh, E. A. 2017. Rpn (YhgA-Like) proteins of Escherichia coli K-12 and their contribution to RecA-independent horizontal transfer. J. Bacteriol., 199(7): e00787-16.
  • Klontz , K. C. and Singh, N. 2015. Treatment of drug-resistant Shigella infections.
  • Expert Rev. Anti. Infect. Ther., 13(1): 69-80.
  • Koonin, E. V. and Tatusov, R. L. 1994. Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity: application of an iterative approach to database search. J. Mol. Biol., 244(1): 125-132.
  • Kotloff , K. L., Riddle, M. S., Platts-Mills , J. A., Pavlinac, P. and Zaidi, A. K. M. 2018. Shigellosis. Lancet., 391: 801-812.
  • Kotloff, K. L. , Winickoff, J. P., Ivanoff, B., Clemens, J. D., Swerdlow, D. L., Sansonetti, P. J., Adak, G. K. and Levine, M. M. 1999. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. World Health Organ., 77(8): 651-66.
  • Kurihara, T. and Esaki, N. 2008. Bacterial hydrolytic dehalogenases and related enzymes: occurrences, reaction mechanisms, and applications. Chem. Rec., 8(2): 67-74.
  • Leipe, D. D., Aravind, L., Grishin, N. V. and Koonin, E. V. 2000. The bacterial replicative helicase DnaB evolved from a RecA duplication. Genome Res., 10(1): 5-16.
  • Linke, D., Riess, T., Autenrieth, I. B., Lupas, A. and Kempf, V. A. 2006. Trimeric autotransporter adhesins: variable structure, common function. Trends Microbiol., 14(6): 264-270.
  • Liu, Y, Bauer, S. C. and Imlay, J. A. 2011. The YaaA protein of the Escherichia coli OxyR regulon lessens hydrogen peroxide toxicity by diminishing the amount of intracellular unincorporated iron. J. Bacteriol., 193(9): 2186-2196.
  • Mandomando , I., Sigaúque, B., Vallès, X., Espasa, M., Sanz, S., Sacarlal, J., Macete, E., Abacassamo, F., Ruiz, J., Gascon, J., Kotloff, K. L., Levine, M. M. and Alonso, P. L. 2007. Epidemiology and clinical presentation of Shigellosis in children less than five years of age in rural Mozambique. Pediatr. Infect. Dis. J., 26(11): 1059-1061.
  • Mascher, T., Helmann, J. D. and Unden, G. 2006. Stimulus perception in bacterial signal-transducing histidine kinases. Microbiol. Mol. Biol. Rev., 70(4): 910-938.
  • Michiel, M., Perchat, N., Perret, A., Tricot, S., Papeil, A., Besnard, M., de Berardinis, V., Salanoubat, M. and Fischer, C. 2012. Microbial urate catabolism: characterization of HpyO, a non-homologous isofunctional isoform of the flavoprotein urate hydroxylase HpxO. Environ. Microbiol. Rep., 4(6): 642-647.
  • Mitchell, A., Chang, H. Y., Daugherty, L., Fraser, M., Hunter, S., Lopez, R., McAnulla, C., McMenamin, C., Nuka, G., Pesseat, S., Sangrador-Vegas, A., Scheremetjew, M., Rato , C., Yong , S. Y., Bateman, A., Punta , M., Attwood, T. K., Sigrist, C. J. A., Redaschi , N., Rivoire, C., Xenarios, I., Kahn, D., Guyot, D., Bork, P., Letunic, I., Gough, J., Oates, M., Haft, D., Huang, H., Natale, D. A., Wu, C.H., Orengo, C., Sillitoe, I., Mi , H., Thomas, P. D. and Finn, R. D. 2015. The interpro protein families database: the classification resource after 15 years. Nucleic Acids Res., 43(Database issue): D213-D221.
  • Mousa, J. J., Yang, Y., Tomkovich, S., Shima, A., Newsome, R. C., Tripathi, P., Oswald, E., Bruner, S. D. and Jobin, C. 2016. MATE transport of the E. coliderived genotoxin colibactin. Nat. Microbiol., 1: 15009.
  • NCBI Resource Coordinators. 2016. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 44(D1), D7-D19.
  • Nishimura, K., Tajima, N., Yoon, Y. H., Oark, S. Y. and Tame, J. R. 2010. Autotransporter passenger proteins: virulence factors with common structural themes. J. Mol. Med. (Berl.), 88(5): 451-458.
  • Nummelin, H., Merckel, M. C., Leo, J. C., Lankinen, H., Skurnik, M. and Goldman, A. 2004. The Yersinia adhesin YadA collagen-binding domain structure is a novel left-handed parallel ß-roll. EMBO J., 23(4): 701-711.
  • Omote, H., Hiasa, M., Matsumoto, T., Otsuka, M. and Moriyama, Y. 2006. The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations. Trends Pharmacol. Sci., 27(11): 587-593.
  • Park, F., Gajiwala, K., Eroshkina, G., Furlong, E., He, D., Batiyenko, Y., Romero, R., Christopher, J., Badger, J., Hendle, J., Lin, J., Peat, T. and Buchanan, S. 2004. Crystal structure of YIGZ, a conserved hypothetical protein from Escherichia coli k12 with a novel fold. Proteins, 55(3): 775-777.
  • Parveen, S. and Reddy, M. 2017. Identification of YfiH (PgeF) as a factor contributing to the maintenance of bacterial peptidoglycan composition. Mol. Microbiol., 105(5): 705-720.
  • Peleg, A., Shifrin, Y., Ilan, O., Nader-Yona, C., Nov, S., Koby, S, Baruch, K., Altuvia, S., Elgrably-Weiss, M., Abe, C. M., Knutton, S., Saper, M. A. and Rosenshine, I. 2005. Identification of an Escherichia coli operon required for formation of the O-antigen capsule. J. Bacteriol., 187(15): 5259-5266.
  • Percudani, R. and Peracchi, A. 2003. A genomic overview of pyridoxal-phosphatedependent enzymes. EMBO Rep., 4(9): 850-854.
  • Radulovic, S., Troyer, J. M., Beier, M. S., Lau, A. O. T. and Azad, A. F. 1999. Identification and molecular analysis of the gene encoding Rickettsia typhi hemolysin. Infect. Immun., 67(11): 6104-6108.
  • Ramirez, M. S. and Tolmasky, M. E. 2010. Aminoglycoside modifying enzymes. Drug Resist. Updat., 13(6): 151-171.
  • Ranjbar, R. and Farahani, A. 2019. Shigella: antibiotic-resistance mechanisms and new horizons for treatment. Infect. Drug Resist., 12: 3137-3167.
  • Rensing, C., Fan, B., Sharma, R., Mitra, B. and Rosen, B. P. 2000. CopA: an Escherichia coli Cu(I)-translocating P-type ATPase. Proc. Natl. Acad. Sci. U.S. A., 97(2): 652-656.
  • Rice, K. C., Turner, M. E., Carney, O. V., Gu, T. and Sang-Joon, A. 2017. Modification of the Streptococcus mutans transcriptome by LrgAB and environmental stressors. Microb. Genom., 3(2): e000104.
  • Richts, B., Rosenberg, J. and Commichau, F. M. 2019. A survey of Pyridoxal 5’-Phosphate-dependent proteins in the Gram-positive model bacterium Bacillus subtilis. Front. Mol. Biosci., 6: 32.
  • Rodríguez-Beltrán, J., Rodríguez-Rojas, A., Guelfo, J. R., Couce, A. and Blázquez, J. 2012. The Escherichia coli SOS gene dinF protects against oxidative stress and bile salts. PLoS One, 7(4): e34791.
  • Sathiyamoorthy, K., Mills, E., Franzmann, T. M., Rosenshine, I. and Saper, M. A. 2011. The crystal structure of Escherichia coli group 4 capsule protein GfcC reveals a domain organization resembling that of Wza. Biochemistry, 50(24): 5465-5476.
  • Schäper, S., Steinchen, W., Krol, E., Altegoer, F., Skotnicka, D., Søgaard-Andersen, L., Bange, G. and Becker, A. 2017. AraC-like transcriptional activator CuxR binds c-di-GMP by a PilZ-like mechanism to regulate extracellular polysaccharide production. Proc. Natl. Acad. Sci. U. S. A., 114(24): E4822-E4831.
  • Schnupf , P. and Sansonetti , P. J. 2019. Shigella pathogenesis: new insights through advanced methodologies. Microbiol. Spectr., 7(2): BAI-0023-2019.
  • Sellés Vidal, L., Kelly, C. L., Mordaka, P. M. and Heap, J. T. 2018. Review of NAD(P) H-dependent oxidoreductases: properties, engineering and application. BBA. Proteins Proteom., 1866(2): 327-347.
  • Shahbaaz, M., Hassan, M. I. and Ahmad, F. 2013. Functional annotation of conserved hypothetical proteins from Haemophilus influenzae Rd KW20. PLoS One, 8(12): e84263.
  • Silva, C. S., Durão, P., Fillat, A., Lindley, P. F., Martins, L. O. and Bento, I. 2012. Crystal structure of the multicopper oxidase from the pathogenic bacterium Campylobacter jejuni CGUG11284: characterization of a metallooxidase. Metallomics, 4(1): 37-47.
  • Sinha, A., Eniyan, K., Sinha, S., Lynn, A. M. and Bajpai, U. 2015. Functional analysis of TPM domain containing Rv2345 of Mycobacterium tuberculosis identifies its phosphatase activity. Protein Expr. Purif., 111: 23-27.
  • Spormann, A. M. 1999. Gliding motility in bacteria: insights from studies of Myxococcus xanthus. Microbiol. Mol. Biol. Rev., 63(3): 621-641.
  • Suzuki, S., Tanigawa, O., Akanuma, G., Nanamiya, H., Kawamura, F., Tagami, K., Nomura, N., Kawabata, T. and Sekine, Y. 2014. Enhanced expression of Bacillus subtilis yaaA can restore both the growth and the sporulation defects caused by mutation of rplB, encoding ribosomal protein L2. Microbiology, 160(6): 1040-1053.
  • Tagliabue, L., Antoniani, D., Maciag, A., Bocci, P., Raffaelli, N. and Landini, P. 2010. The diguanylate cyclase YddV controls production of the exopolysaccharide poly-N-acetylglucosamine (PNAG) through regulation of the PNAG biosynthetic pgaABCD operon. Microbiology, 156(10): 2901-2911.
  • Toth, M., Frase, H., Antunes, N. T. and Vakulenko, S. B. 2013. Novel aminoglycoside 2´´-phosphotransferase identified in a gram-negative pathogen. Antimicrob. Agents. Chemother., 57(1): 452-457.
  • Trofa, A. F., Ueno-Olsen, H., Oiwa, R. and Yoshikawa, M. 1999. Dr. Kiyoshi Shiga: discoverer of the dysentery Bacillus. Clin. Infect. Dis., 29(5): 1303-1306.
  • Tuckerman, J. R., Gonzalez, G. and Gilles-Gonzalez, M. A. 2011. Cyclic di-GMP activation of polynucleotide phosphorylase signal-dependent RNA processing. J. Mol. Biol., 407(5): 633-639.
  • Tuckerman, J. R., Gonzalez, G., Sousa, E. H. S., Wan, X., Saito, J. A., Alam, M. and Gilles-Gonzalez, M. A. 2009. An oxygen-sensing diguanylate cyclase and phosphodiesterase couple for c-di-GMP control. Biochemistry. 48(41): 9764-9774.
  • Wang, S., Yang, D., Wu, X., Wang, Y., Wang, D., Tian, M., Li, T., Qi, J., Wang, X., Ding, C. and Yu, S. 2018. Autotransporter MisL of Salmonella enterica serotype Typhimurium facilitates bacterial aggregation and biofilm formation. FEMS Microbiol. Lett., 365(17):10.1093/femsle/fny142.
  • Weinitschke, S., Denger, K., Cook, A. M. and Smits, T. H. M. 2007. The DUF81 protein TauE in Cupriavidus necator H16, a sulfite exporter in the metabolism of C2 sulfonates. Microbiology, 153(9): 3055-3060.
  • Wells, T. J., Tree, J. J., Ulett, G. C. and Schembri, M. A. 2007. Autotransporter proteins: novel targets at the bacterial cell surface. FEMS Microbiol. Lett., 274(2): 163-172.
  • Wexler, M., Sargent, F., Jack, R. L., Stanley, N. R., Bogsch, E. G., Robinson, C., Berks, B. C. and Palmer, T. 2000. TatD is a cytoplasmic protein with DNase activity. No requirement for TatD family proteins in sec-independent protein export. J. Biol. Chem., 275(22): 16717-16722.
  • Whitworth, T., Popov, V. L., Yu, X-J., Walker, D. H. and Bouyer, D. H. 2005. Expression of the Rickettsia prowazekii pld or tlyC gene in Salmonella enterica Serovar Typhimurium mediates phagosomal escape. Infect. Immun., 73(10): 6668-6673.
  • Yousafi , Q., Kanwal , S., Rashid , H., Khan , M. S., Saleem , S. and Aslam, M. 2019. In silico structural and functional characterization and phylogenetic study of alkaline phosphatase in bacterium, Rhizobium Leguminosarum (Frank 1879). Comput. Biol. Chem., 83: 107142.
  • Yu, C-S., Chen, Y-C., Lu, C-H and Hwang, J-K. 2006. Prediction of protein subcellular localization. Proteins, 64(3): 643-651.
  • Yu, N. Y., Wagner, J. R., Laird, M. R., Melli, G., Rey, S., Lo, R., Dao, P., Sahinalp, S. C., Ester, M., Foster, L. J. and Brinkman, F. S. L. 2010. PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics, 26(13): 1608-1615.
  • Zhang, J., De Masi, L., John, B., Chen, W. and Schifferli, D. M. 2014. Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella. Microb. Cell Fact., 13: 80.
  • Zhulin, I. B., Nikolskaya, A. N. and Galperin, M. Y. 2003. Common extracellular sensory domains in transmembrane receptors for diverse signal transduction pathways in bacteria and archaea. J. Bacteriol., 185(1): 285-294.

Abstract Views: 7

PDF Views: 0




  • Functional Annotation of Pathogenesis Proteins in Shigella flexneri using Comparative Genomics

Abstract Views: 7  |  PDF Views: 0

Authors

Sarmishta Mukhopadhyay
Department of Zoology, Government General Degree College, Singur, West Bengal, India
Sayak Ganguli
Department of Biotechnology, St. Xavier’s College, Kolkata- 700016, India
Santanu Chakrabarti
Department of Zoology, Government General Degree College, Singur, West Bengal, India

Abstract


The Gram-negative bacteria, Shigella species, is a predominant diarrheal pathogen and itself accounts for 15% of the diarrheal episodes occurring globally. Shigella enters the human body through ingestion of contaminated food and water and on reaching the intestine, dismantles the epithelial barrier, generating symptoms varying from mild to severe bloody diarrhea. Widespread diversity of Shigella species and the emergence of multi-drug resistant strains in recent years has made it extremely enigmatic to design a successful drug to combat shigellosis. This work focusses on comparative genomics methods to identify and annotate hypothetical proteins from the Shigella flexneri genome in quest of identifying novel druggable targets.

Keywords


Shigellosis, Hypothetical Proteins, Comparative Genomics, Drug Targets.

References