title: Susceptibility of intracellular Coxiella burnetii to antimicrobial peptides in mouse fibroblast cells.
abstract: Q fever is a zoonotic disease caused by Coxiella burnetii, an obligate intracellular bacterium that resides inside a phagolysosome-like niche. Chronic Q fever is typified by endocarditis, and is treated with multiple antibiotics for at least 18 months. The discovery of clinical C. burnetii isolates resistant to the first-line antibiotic doxycycline, and the problematic nature of chronic Q fever treatment have demonstrated the need for improved treatment regimes. To search for alternative antimicrobial agents, we assessed the effect of 26 antimicrobial peptides (AMPs) on the intracellular growth of C. burnetii in L929 cells at a concentration of 25 µM or their maximal non-cytotoxic concentration. Among the peptides tested, A3-APO, Cath-BF, δ-Hemolysin, Octa-1, P5 and Pleurocidin were able to significantly reduce both the total bacterial cell number and the host cell bacterial burden (average bacterial number per host cell). Combining selected AMPs with Chariot, a non-covalent carrier peptide, did not increase treatment potency when non-cytotoxic concentrations were used, with the exception of P5, which remained active at a concentration of 1.6 µM (1.8 µg/mL). Combining AMPs with each other did not further improve AMP potency, with some treatment combinations increasing the growth rate of C. burnetii by >3-fold. This is the first description of AMP cellular penetration to exhibit inhibitory affect on intracellular C. burnetii growth. These results are the first step in the development of a non-traditional antibiotic treatment for Q fever.
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Unsworth
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Dawson
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.affiliation: Land Division, Defence Science and Technology Organisation, 506 Lorimer Street, Fishermans Bend, Melbourne, Victoria 3207, Australia. chun.liu@dsto.defence.gov.au.
authors.forename: Chun-Qiang
authors.initials: CQ
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D016997:Coxiella burnetii / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology*; D006461:Hemolysis / Q000187:drug effects; D042541:Intracellular Space / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides