Phagolysosomal Alkalinization and the Bactericidal Effect of Antibiotics: TheCoxiella burnetii Paradigm
Identifieur interne : 000440 ( France/Analysis ); précédent : 000439; suivant : 000441Phagolysosomal Alkalinization and the Bactericidal Effect of Antibiotics: TheCoxiella burnetii Paradigm
Auteurs : Max Maurin [France] ; Anne Marie Benoliel [France] ; Pierre Bongrand [France] ; Didier Raoult [France]Source :
- Journal of Infectious Diseases [ 0022-1899 ] ; 1992.
Abstract
Most infections due to intracellular bacteria respond poorly to antibiotic treatment, The chemical conditions within the subcellular site of bacteria may change antibiotic activity. Coxiella burnetii multiplies within phagolysosomes. The antimicrobial activity of antibiotics combined with the lysosomotropic agents amantadine (1 µg/mL), chloroquine (1 µg/mL), and ammonium chloride (1 mg/mL), which alkalinized Coxiella burnetii-containing phagolysosomes from pH 4.8 to 5.3, 5.7, and 6.8, respectively, was evaluated. Percentages of residual viable bacteria (RVB) in cell cultures were significantly reduced after exposure to combinations of doxycycline (4 µg/mL) with amantadine (RVB = 18.2% ± 8.7%, P < .05), chloroquine (RVB = 0.64% ± 0.38%, P < .01), or ammonium chloride (RVB = 0.29% ± 0.17%, P < .01); the same was seen with pefloxacin (1 µg/mL) with chloroquine (RVB = 27.6% ± 10.8%, P < .05) or ammonium chloride (RVB = 3.72% ± 1.1%, P < .05). Such bactericidal activity correlated with increased phagolysosomal pH, as determined by Pearson's correlation coefficient, suggesting that phagolysosomal alkalinization is critical for the bactericidal effect of antibiotics.
Url:
DOI: 10.1093/infdis/166.5.1097
Affiliations:
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<front><div type="abstract">Most infections due to intracellular bacteria respond poorly to antibiotic treatment, The chemical conditions within the subcellular site of bacteria may change antibiotic activity. Coxiella burnetii multiplies within phagolysosomes. The antimicrobial activity of antibiotics combined with the lysosomotropic agents amantadine (1 µg/mL), chloroquine (1 µg/mL), and ammonium chloride (1 mg/mL), which alkalinized Coxiella burnetii-containing phagolysosomes from pH 4.8 to 5.3, 5.7, and 6.8, respectively, was evaluated. Percentages of residual viable bacteria (RVB) in cell cultures were significantly reduced after exposure to combinations of doxycycline (4 µg/mL) with amantadine (RVB = 18.2% ± 8.7%, P < .05), chloroquine (RVB = 0.64% ± 0.38%, P < .01), or ammonium chloride (RVB = 0.29% ± 0.17%, P < .01); the same was seen with pefloxacin (1 µg/mL) with chloroquine (RVB = 27.6% ± 10.8%, P < .05) or ammonium chloride (RVB = 3.72% ± 1.1%, P < .05). Such bactericidal activity correlated with increased phagolysosomal pH, as determined by Pearson's correlation coefficient, suggesting that phagolysosomal alkalinization is critical for the bactericidal effect of antibiotics.</div>
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