Phagolysosomal Alkalinization and the Bactericidal Effect of Antibiotics: The Coxiella burnetii Paradigm

摘要: Most infections due to intracellular bacteria respond poorly antibiotic treatment. The chemical conditions within the subcellular site of may change activity. Coxiella burnetii multiplies phagolysosomes. antimicrobial activity antibiotics combined with lysosomotropic agents amantadine (1 microgram/mL), chloroquine and ammonium chloride mg/mL), which alkalinized burnetii-containing phagolysosomes from pH 4.8 5.3, 5.7, 6.8, respectively, was evaluated. Percentages residual viable (RVB) in cell cultures were significantly reduced after exposure combinations doxycycline (4 micrograms/mL) (RVB = 18.2% +/- 8.7%, P < .05), 0.64% 0.38%, .01), or 0.29% 0.17%, .01); same seen pefloxacin microgram/mL) 27.6% 10.8%, .05) 3.72% 1.1%, .05). Such bactericidal correlated increased phagolysosomal pH, as determined by Pearson's correlation coefficient, suggesting that alkalinization is critical for effect antibiotics.