New players in the same old game: a system level in silico study to predict type III secretion system and effector proteins in bacterial genomes reveals common themes in T3SS mediated pathogenesis

BMC Research Notes

Manonmani Arunachalam³  Sunando Datta²  Vineet Sadarangani¹ 

[1] National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India;Indian Institutes of Science Education and Research, Bhopal 462023, India;UT Southwestern Medical Center, Department of Molecular Biology, Dallas, TX 75235, USA

关键词: Cytoskeletal structure;    Intracellular pathogen;    Effector;    T3SS;   

Others  :  1142053
DOI  :  10.1186/1756-0500-6-297

 received in 2012-12-13, accepted in 2013-07-10,  发布年份 2013

【 摘 要 】

Background

Type III secretion system (T3SS) plays an important role in virulence or symbiosis of many pathogenic or symbiotic bacteria [CHM 2:291–294, 2007; Physiology (Bethesda) 20:326–339, 2005]. T3SS acts like a tunnel between a bacterium and its host through which the bacterium injects ‘effector’ proteins into the latter [Nature 444:567–573, 2006; COSB 18:258–266, 2008]. The effectors spatially and temporally modify the host signalling pathways [FEMS Microbiol Rev 35:1100–1125, 2011; Cell Host Microbe5:571–579, 2009]. In spite its crucial role in host-pathogen interaction, the study of T3SS and the associated effectors has been limited to a few bacteria [Cell Microbiol 13:1858–1869, 2011; Nat Rev Microbiol 6:11–16, 2008; Mol Microbiol 80:1420–1438, 2011]. Before one set out to perform systematic experimental studies on an unknown set of bacteria it would be beneficial to identify the potential candidates by developing an in silico screening algorithm. A system level study would also be advantageous over traditional laboratory methods to extract an overriding theme for host-pathogen interaction, if any, from the vast resources of data generated by sequencing multiple bacterial genomes.

Results

We have developed an in silico protocol in which the most conserved set of T3SS proteins was used as the query against the entire bacterial database with increasingly stringent search parameters. It enabled us to identify several uncharacterized T3SS positive bacteria. We adopted a similar strategy to predict the presence of the already known effectors in the newly identified T3SS positive bacteria. The huge resources of biochemical data [FEMS Microbiol Rev 35:1100–1125, 2011; Cell Host Microbe 5:571–579, 2009; BMC Bioinformatics 7(11):S4, 2010] on the T3SS effectors enabled us to search for the common theme in T3SS mediated pathogenesis. We identified few cellular signalling networks in the host, which are manipulated by most of the T3SS containing pathogens. We went on to look for correlation, if any, between the biological quirks of a particular class of bacteria with the effectors they harbour. We could pin point few effectors, which were enriched in certain classes of bacteria.

Conclusion

The current study would open up new avenues to explore many uncharacterized T3SS positive bacteria. The experimental validation of the predictions from this study will unravel a generalized mechanism for T3SS positive bacterial infection into host cell.

【 授权许可】

   
2013 Sadarangani et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Fronzes R, Christie PJ, Waksman G: The structural biology of type IV secretion systems. Nat Rev Microbiol 2009, 7:703-714.
• [2]Galan JE, Wolf-Watz H: Protein delivery into eukaryotic cells by type III secretion machines. Nature 2006, 444:567-573.
• [3]Moraes TF, Spreter T, Strynadka NC: Piecing together the type III injectisome of bacterial pathogens. Curr Opin Struct Biol 2008, 18:258-266.
• [4]Preston GM: Metropolitan microbes: type III secretion in multihost symbionts. Cell Host Microbe 2007, 2:291-294.
• [5]Dean P: Functional domains and motifs of bacterial type III effector proteins and their roles in infection. FEMS Microbiol Rev 2011, 35:1100-1125.
• [6]Marteyn B, Gazi A, Sansonetti P: Shigella: a model of virulence regulation in vivo. Gut Microbes 2012, 3:104-120.
• [7]Cornelis GR: The type III secretion injectisome. Nat Rev Microbiol 2006, 4:811-825.
• [8]Izore T, Job V, Dessen A: Biogenesis, regulation, and targeting of the type III secretion system. Structure 2011, 19:603-612.
• [9]Troisfontaines P, Cornelis GR: Type III secretion: more systems than you think. Physiology (Bethesda) 2005, 20:326-339.
• [10]Diepold A, Amstutz M, Abel S, Sorg I, Jenal U, Cornelis GR: Deciphering the assembly of the Yersinia type III secretion injectisome. EMBO J 2010, 29:1928-1940.
• [11]Galan JE: Common themes in the design and function of bacterial effectors. Cell Host Microbe 2009, 5:571-579.
• [12]Stavrinides J, McCann HC, Guttman DS: Host-pathogen interplay and the evolution of bacterial effectors. Cell Microbiol 2008, 10:285-292.
• [13]Agbor TA, McCormick BA: Salmonella effectors: important players modulating host cell function during infection. Cell Microbiol 2011, 13:1858-1869.
• [14]Ogawa M, Handa Y, Ashida H, Suzuki M, Sasakawa C: The versatility of Shigella effectors. Nat Rev Microbiol 2008, 6:11-16.
• [15]Wong AR, Pearson JS, Bright MD, Munera D, Robinson KS, Lee SF, Frankel G, Hartland EL: Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements. Mol Microbiol 2011, 80:1420-1438.
• [16]Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 1990, 215:403-410.
• [17]Thompson JD, Higgins DG, Gibson TJ, Clustal W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22:4673-4680.
• [18]Betts HJ, Twiggs LE, Sal MS, Wyrick PB, Fields KA: Bioinformatic and biochemical evidence for the identification of the type III secretion system needle protein of Chlamydia trachomatis. J Bacteriol 2008, 190:1680-1690.
• [19]Knodler LA, Vallance BA, Hensel M, Jackel D, Finlay BB, Steele-Mortimer O: Salmonella type III effectors PipB and PipB2 are targeted to detergent-resistant microdomains on internal host cell membranes. Mol Microbiol 2003, 49:685-704.
• [20]Waterman SR, Holden DW: Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell Microbiol 2003, 5:501-511.
• [21]Haraga A, Miller SI: A Salmonella enterica serovar typhimurium translocated leucine-rich repeat effector protein inhibits NF-kappa B-dependent gene expression. Infect Immun 2003, 71:4052-4058.
• [22]Rohde JR, Breitkreutz A, Chenal A, Sansonetti PJ, Parsot C: Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe 2007, 1:77-83.
• [23]Bernal-Bayard J, Cardenal-Munoz E, Ramos-Morales F: The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3. J Biol Chem 2010, 285:16360-16368.
• [24]Bernal-Bayard J, Ramos-Morales F: Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin. J Biol Chem 2009, 284:27587-27595.
• [25]Tay DM, Govindarajan KR, Khan AM, Ong TY, Samad HM, Soh WW, Tong M, Zhang F, Tan TW: T3SEdb: data warehousing of virulence effectors secreted by the bacterial type III secretion system. BMC Bioinforma 2010, 7(11):S4.
• [26]Jehl MA, Arnold R, Rattei T: Effective–a database of predicted secreted bacterial proteins. Nucleic Acids Res 2011, 39:D591-D592.
• [27]Yang Y, Zhao J, Morgan RL, Ma W, Jiang T: Computational prediction of type III secreted proteins from Gram-negative bacteria. BMC Bioinforma 2010, 1(11):S47.