Phagolysosomal Alkalinization and the Bactericidal Effect of Antibiotics: TheCoxiella burnetii Paradigm
Identifieur interne : 002E28 ( Main/Exploration ); précédent : 002E27; suivant : 002E29Phagolysosomal 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
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<hi rend="italic">Coxiella burnetii</hi> Paradigm</title><author><name sortKey="Maurin, Max" sort="Maurin, Max" uniqKey="Maurin M" first="Max" last="Maurin">Max Maurin</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Unité des Rickettsies, Faculté de Médecine de la Timone, and Laboratoire d'Immunologie, Hopital Ste. Marguerite, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Benoliel, Anne Marie" sort="Benoliel, Anne Marie" uniqKey="Benoliel A" first="Anne Marie" last="Benoliel">Anne Marie Benoliel</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Unité des Rickettsies, Faculté de Médecine de la Timone, and Laboratoire d'Immunologie, Hopital Ste. Marguerite, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Bongrand, Pierre" sort="Bongrand, Pierre" uniqKey="Bongrand P" first="Pierre" last="Bongrand">Pierre Bongrand</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Unité des Rickettsies, Faculté de Médecine de la Timone, and Laboratoire d'Immunologie, Hopital Ste. Marguerite, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Unité des Rickettsies, Faculté de Médecine de la Timone, and Laboratoire d'Immunologie, Hopital Ste. Marguerite, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Reprints or correspondence: Pr. Didier Raoult, Unité des rickettsies, Faculté de médecine de la Timone, Bd. Jean Moulin, 13385 Marseille cedex 5</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Infectious Diseases</title><title level="j" type="abbrev">J Infect Dis.</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="1992-11">1992</date><biblScope unit="vol">166</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="1097">1097</biblScope><biblScope unit="page" to="1102">1102</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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></front></TEI><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Maurin, Max" sort="Maurin, Max" uniqKey="Maurin M" first="Max" last="Maurin">Max Maurin</name></region><name sortKey="Benoliel, Anne Marie" sort="Benoliel, Anne Marie" uniqKey="Benoliel A" first="Anne Marie" last="Benoliel">Anne Marie Benoliel</name><name sortKey="Bongrand, Pierre" sort="Bongrand, Pierre" uniqKey="Bongrand P" first="Pierre" last="Bongrand">Pierre Bongrand</name><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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