title: Understanding HIV-Mycobacteria synergism through comparative proteomics of intra-phagosomal mycobacteria during mono- and HIV co-infection.
abstract: Mycobacterium tuberculosis (Mtb) is the most common co-infection in HIV patients and a serious co-epidemic. Apart from increasing the risk of reactivation of latent tuberculosis (TB), HIV infection also permits opportunistic infection of environmental non-pathogenic mycobacteria. To gain insights into mycobacterial survival inside host macrophages and identify mycobacterial proteins or processes that influence HIV propagation during co-infection, we employed proteomics approach to identify differentially expressed intracellular mycobacterial proteins during mono- and HIV co-infection of human THP-1 derived macrophage cell lines. Of the 92 proteins identified, 30 proteins were upregulated during mycobacterial mono-infection and 40 proteins during HIV-mycobacteria co-infection. We observed down-regulation of toxin-antitoxin (TA) modules, up-regulation of cation transporters, Type VII (Esx) secretion systems, proteins involved in cell wall lipid or protein metabolism, glyoxalate pathway and branched chain amino-acid synthesis during co-infection. The bearings of these mycobacterial factors or processes on HIV propagation during co-infection, as inferred from the proteomics data, were validated using deletion mutants of mycobacteria. The analyses revealed mycobacterial factors that possibly via modulating the host environment, increased viral titers during co-infection. The study provides new leads for investigations towards hitherto unknown molecular mechanisms explaining HIV-mycobacteria synergism, helping address diagnostics and treatment challenges for effective co-epidemic management.
authors.affiliation: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Ganji
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra, India.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Dhali
authors.affiliation: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, India.
authors.forename: Arshad
authors.initials: A
authors.lastname: Rizvi
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra, India.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Rapole
authors.affiliation: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, India.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009164:Mycobacterium Infections / Q000235:genetics / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010588:Phagosomes / Q000382:microbiology; D040901:Proteomics
chemical_list: D001426:Bacterial Proteins