Chandrajit Lahiri1, Shrikant Pawar2, Radhakrishnan Sabarinathan3, Md Izhar Ashraf4, Yamini Chand5, Dipshikha Chakravortty6. 1. Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India. Electronic address: chandrajit@imsc.res.in. 2. Department of Biology, Georgia State University, Atlanta, GA 30303, USA. Electronic address: spawar2@gsu.edu. 3. Bioinformatics Center, Indian Institute of Science, Bangalore 560012, India. Electronic address: sabari.iisc@gmail.com. 4. B.S. Abdur Rahman University, Vandalur, Chennai 600048, India. Electronic address: ashraf@imsc.res.in. 5. Department of Bioinformatics, Karunya University, Coimbatore 641114, India. Electronic address: yaminichand@karunya.edu.in. 6. Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India. Electronic address: dipa@mcbl.iisc.ernet.in.
Abstract
BACKGROUND: Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively. RESULTS: We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection. CONCLUSIONS: A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents.
BACKGROUND: Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively. RESULTS: We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection. CONCLUSIONS: A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents.
Authors: Jamal S M Sabir; Abdelfatteh El Omri; Noor A Shaik; Babajan Banaganapalli; Majed A Al-Shaeri; Naser A Alkenani; Nahid H Hajrah; Zuhier A Awan; Houda Zrelli; Ramu Elango; Muhummadh Khan Journal: PLoS One Date: 2019-04-23 Impact factor: 3.240
Authors: Jamal Sabir M Sabir; Abdelfatteh El Omri; Babajan Banaganapalli; Nada Aljuaid; Abdulkader M Shaikh Omar; Abdulmalik Altaf; Nahid H Hajrah; Houda Zrelli; Leila Arfaoui; Ramu Elango; Mona G Alharbi; Alawiah M Alhebshi; Robert K Jansen; Noor A Shaik; Muhummadh Khan Journal: PLoS One Date: 2020-02-06 Impact factor: 3.240
Authors: Luis E Romero-González; Deyanira Pérez-Morales; Daniel Cortés-Avalos; Edwin Vázquez-Guerrero; Denisse A Paredes-Hernández; Paulina Estrada-de Los Santos; Lourdes Villa-Tanaca; Miguel A De la Cruz; Víctor H Bustamante; J Antonio Ibarra Journal: PLoS One Date: 2020-10-29 Impact factor: 3.240