Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host

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dc.contributor.authorRapanoel, Holifidy Aen_ZA
dc.contributor.authorMazandu, Gaston Ken_ZA
dc.contributor.authorMulder, Nicola Jen_ZA
dc.date.accessioned2015-12-28T06:47:37Z
dc.date.available2015-12-28T06:47:37Z
dc.date.issued2013en_ZA
dc.description.abstractThe outcome of infection by Mycobacterium tuberculosis (Mtb) depends greatly on how the host responds to the bacteria and how the bacteria manipulates the host, which is facilitated by protein-protein interactions. Thus, to understand this process, there is a need for elucidating protein interactions between human and Mtb, which may enable us to characterize specific molecular mechanisms allowing the bacteria to persist and survive under different environmental conditions. In this work, we used the interologs method based on experimentally verified intra-species and inter-species interactions to predict human-Mtb functional interactions. These interactions were further filtered using known human-Mtb interactions and genes that are differentially expressed during infection, producing 190 interactions. Further analysis of the subcellular location of proteins involved in these human-Mtb interactions confirms feasibility of these interactions. We also conducted functional analysis of human and Mtb proteins involved in these interactions, checking whether these proteins play a role in infection and/or disease, and enriching Mtb proteins in a previously predicted list of drug targets. We found that the biological processes of the human interacting proteins suggested their involvement in apoptosis and production of nitric oxide, whereas those of the Mtb interacting proteins were relevant to the intracellular environment of Mtb in the host. Mapping these proteins onto KEGG pathways highlighted proteins belonging to the tuberculosis pathway and also suggested that Mtb proteins might use the host to acquire nutrients, which is in agreement with the intracellular lifestyle of Mtb. This indicates that these interactions can shed light on the interplay between Mtb and its human host and thus, contribute to the process of designing novel drugs with new biological mechanisms of action.en_ZA
dc.identifier.apacitationRapanoel, H. A., Mazandu, G. K., & Mulder, N. J. (2013). Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host. <i>PLoS One</i>, http://hdl.handle.net/11427/16038en_ZA
dc.identifier.chicagocitationRapanoel, Holifidy A, Gaston K Mazandu, and Nicola J Mulder "Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16038en_ZA
dc.identifier.citationRapanoel, H. A., Mazandu, G. K., & Mulder, N. J. (2013). Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host. PloS one, 8(7), e67472. doi:10.1371/journal.pone.0067472en_ZA
dc.identifier.ris TY - Journal Article AU - Rapanoel, Holifidy A AU - Mazandu, Gaston K AU - Mulder, Nicola J AB - The outcome of infection by Mycobacterium tuberculosis (Mtb) depends greatly on how the host responds to the bacteria and how the bacteria manipulates the host, which is facilitated by protein-protein interactions. Thus, to understand this process, there is a need for elucidating protein interactions between human and Mtb, which may enable us to characterize specific molecular mechanisms allowing the bacteria to persist and survive under different environmental conditions. In this work, we used the interologs method based on experimentally verified intra-species and inter-species interactions to predict human-Mtb functional interactions. These interactions were further filtered using known human-Mtb interactions and genes that are differentially expressed during infection, producing 190 interactions. Further analysis of the subcellular location of proteins involved in these human-Mtb interactions confirms feasibility of these interactions. We also conducted functional analysis of human and Mtb proteins involved in these interactions, checking whether these proteins play a role in infection and/or disease, and enriching Mtb proteins in a previously predicted list of drug targets. We found that the biological processes of the human interacting proteins suggested their involvement in apoptosis and production of nitric oxide, whereas those of the Mtb interacting proteins were relevant to the intracellular environment of Mtb in the host. Mapping these proteins onto KEGG pathways highlighted proteins belonging to the tuberculosis pathway and also suggested that Mtb proteins might use the host to acquire nutrients, which is in agreement with the intracellular lifestyle of Mtb. This indicates that these interactions can shed light on the interplay between Mtb and its human host and thus, contribute to the process of designing novel drugs with new biological mechanisms of action. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0067472 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host TI - Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host UR - http://hdl.handle.net/11427/16038 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16038
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0067472
dc.identifier.vancouvercitationRapanoel HA, Mazandu GK, Mulder NJ. Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host. PLoS One. 2013; http://hdl.handle.net/11427/16038.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Rapanoel et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherProtein interactionsen_ZA
dc.subject.otherHost-pathogen interactionsen_ZA
dc.subject.otherGene ontologiesen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherMembrane proteinsen_ZA
dc.subject.otherProtein interaction networksen_ZA
dc.subject.otherDrug interactionsen_ZA
dc.titlePredicting and analyzing interactions between Mycobacterium tuberculosis and its human hosten_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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