The effect of treatment with a protease inhibitor on mycobacterial infection.
Mycobacterial infection occurs frequently in patients that receive protease inhibitors, which are drugs used to treat AIDS, but are known for metabolic effects. Proteases of microbial antigens have been recognized as important regulators of host inflammation and cellular response. To evaluate protease inhibitor effect on a mycobacterial infection, a pilot animal model was established. Mycobacterium bovis (bacillus Calmette-Guerin, or BCG) infection was compared in rats that received ritonavir and those that did not. Tissues and serum from one drug-treated and one control were analyzed weekly. Fewer acid-fast bacilli (AFBs) were consistently found in the drug-treated group by 3 separate measures: culture of tissue homogenates on solid media, tissue granuloma counts on organ sections, and staining of tissues for AFBs. Possible mechanisms of the observed relative resistance to BCG infection in ritonavir-treated rats were explored, by evaluating M. bovis cell wall lipids and proteins and by measuring infection-related cytokines in treated and control animals.
Kabbesh
Mohammad
M
University of Missouri-Kansas City, School of Medicine, Kansas City, MO 64108, USA.
Koomer
Ajoy
A
Molteni
Agostino
A
Amajoyi
Robert
R
Quinn
Tim
T
Herndon
Betty
B
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis; D002473:Cell Wall / Q000737:chemistry; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000382:microbiology; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000382:microbiology; D014280:Triglycerides / Q000097:blood
D001426:Bacterial Proteins; D017320:HIV Protease Inhibitors; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D019438:Ritonavir