biostudies-literatureUnknown9(5)Vahlas ZTuberculosis (TB) is a significant aggravating factor in individuals living with HIV-1, the causative agent for AIDS. Both <i>Mycobacterium tuberculosis</i> (Mtb), the bacterium responsible for TB, and HIV-1 target macrophages. Understanding how Mtb subverts these cells may facilitate the identification of new druggable targets. Here, we explored how TB can induce macrophages to form tunneling nanotubes (TNT), promoting HIV-1 spread. We found that TB triggers metabolic rewiring of macrophages, increasing their glycolytic ATP production. Using several pharmacological inhibitors, glucose deprivation, and glucose or galactose supplementation, we discovered that disrupting aerobic glycolysis significantly reduces HIV-1 infection in these macrophages. Glycolysis is essential for tunneling nanotLife science alliancee202503333https://www.ebi.ac.uk/biostudies/studies/S-EPMC12920055biostudies-literatureGlycolysis inhibition in tuberculosis-driven metabolic rewiring reduces HIV-1 spread in macrophages.PMC12920055Barros JCorti MVahlas ZFaivre NBen Neji MMaio MLucas ALetisse FVerollet CRaynaud-Messina BVu Manh TPHertel QMonard SCBlanchet FPingret MDeyts CNeyrolles OFried SPoincloux RLugo-Villarino GBalboa LfalseGlycolysis inhibition in tuberculosis-driven metabolic rewiring reduces HIV-1 spread in macrophages.Tuberculosis (TB) is a significant aggravating factor in individuals living with HIV-1, the causative agent for AIDS. Both <i>Mycobacterium tuberculosis</i> (Mtb), the bacterium responsible for TB, and HIV-1 target macrophages. Understanding how Mtb subverts these cells may facilitate the identification of new druggable targets. Here, we explored how TB can induce macrophages to form tunneling nanotubes (TNT), promoting HIV-1 spread. We found that TB triggers metabolic rewiring of macrophages, increasing their glycolytic ATP production. Using several pharmacological inhibitors, glucose deprivation, and glucose or galactose supplementation, we discovered that disrupting aerobic glycolysis significantly reduces HIV-1 infection in these macrophages. Glycolysis is essential for tunneling nanot2026-01-01T00:00:00Z2026 May2026-07-16T13:00:19.387Z2026-07-09T10:56:17.152ZS-EPMC129200554171413710.26508/lsa.202503333