Mycobacterium tuberculosis induces expression of P-glycoprotein in promonocytic U1 cells chronically infected with HIV type 1.
A productive infection with HIV-1 is associated with an increased expression of a 170 kd plasma membrane P-glycoprotein (P-gp), that functions as a metabolically active drug efflux pump, in human T and macrophage cell lines. In this investigation we show that phagocytosis of M. tuberculosis by U1 cells, that are chronically infected with HIV-1 but produce minimal or no virus, resulted in an expression of P-gp that was associated with increased production of HIV-1 p24 antigen. In addition, U1 cells that had phagocytosed M. tuberculosis accumulated significantly less intracellular isoniazid (INH) as compared to U1 cells. Furthermore, verapamil, that binds to P-gp, increased the intracellular accumulation of INH and the sensitivity of M. tuberculosis to INH. These data suggest induction of P-gp expression may be one of the host mechanisms for the development of multidrug resistant M. tuberculosis in HIV 1 infection.
Gollapudi
S
S
Division of Basic and Clinical Immunology, University of California, Irvine.
Reddy
M
M
Gangadharam
P
P
Tsuruo
T
T
Gupta
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007538:Isoniazid / Q000378:metabolism / Q000633:toxicity; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014779:Virus Replication
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014700:Verapamil; D007538:Isoniazid