Understanding HIV-Mycobacteria synergism through comparative proteomics of intra-phagosomal mycobacteria during mono- and HIV co-infection

• Published in: Scientific reports 2016-02, Vol.6 (1), p.22060-22060, Article 22060
• Main Authors: Ganji, Rakesh, Dhali, Snigdha, Rizvi, Arshad, Rapole, Srikanth, Banerjee, Sharmistha
• Format: Article
• Language: English
• Subjects: 45/70; 631/326; 631/326/88; AIDS-Related Opportunistic Infections - genetics; AIDS-Related Opportunistic Infections - metabolism; Antitoxins; Bacterial Proteins - genetics; Cell lines; Cell walls; Clonal deletion; Deletion mutant; Epidemics; Gene Expression Regulation, Bacterial; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Infections; Lipid metabolism; Macrophages; Macrophages - microbiology; Molecular modelling; multidisciplinary; Mycobacterium Infections - genetics; Mycobacterium Infections - metabolism; Mycobacterium tuberculosis - metabolism; Opportunist infection; Phagosomes - microbiology; Protein turnover; Proteins; Proteomics; Science; Science (multidisciplinary); Secretion; Synergism; Toxins; Tuberculosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22060

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.