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Killing kinetics of intracellular Afipia felis treated with amikacin
H Le Pocher1, P Brouqui, D Raoult
1Unité des Rickettsies, CNRS UPRESA 6020, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
Abstract:
Afipia felis is a facultative intracellular bacterium which multiplies in macrophages following inhibition of phagosome-lysosome (P-L) fusion. When A. felis-infected cells are incubated for 72 h with various antibiotics, only aminoglycosides are found to be bactericidal. We therefore studied the killing of intracellular A. felis by amikacin, and its relationship with the restoration of P-L fusion. Amikacin reduced the number of A. felis from 8.5 x 10(5) to 3.5 x 102 cfu/mL within 94 h. P-L fusion was restored after 30-40 h of incubation with amikacin. Both mechanisms may participate in the intracellular killing of bacteria.
Insights
Amikacin effectively kills intracellular Afipia felis bacteria by restoring phagosome-lysosome fusion in macrophages. This study highlights amikacin
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Afipia felis is a facultative intracellular bacterium that replicates within macrophages.
- Bacterial survival relies on inhibiting phagosome-lysosome (P-L) fusion.
- Aminoglycosides are the only antibiotics found to be bactericidal against intracellular A. felis.
Purpose of the Study:
- To investigate the bactericidal effect of amikacin on intracellular Afipia felis.
- To determine the relationship between amikacin treatment and the restoration of P-L fusion.
- To elucidate the mechanisms of intracellular bacterial killing by amikacin.
Main Methods:
- Infection of cells with Afipia felis.
- Incubation with amikacin.
- Quantification of intracellular bacterial load (colony-forming units/mL).
- Assessment of phagosome-lysosome fusion restoration.
Main Results:
- Amikacin significantly reduced intracellular A. felis counts from 8.5 x 10(5) to 3.5 x 10(2) cfu/mL within 94 hours.
- Phagosome-lysosome fusion was restored after 30-40 hours of amikacin incubation.
- Both bacterial reduction and P-L fusion restoration occurred concurrently.
Conclusions:
- Amikacin exhibits potent bactericidal activity against intracellular Afipia felis.
- Restoration of phagosome-lysosome fusion is a key mechanism in amikacin's efficacy.
- Combined effects of direct killing and restored cellular defense contribute to bacterial clearance.