title: Impairment of innate immune killing mechanisms by bacteriostatic antibiotics.
abstract: Antibiotics are designed to support host defense in controlling infection. Here we describe a paradoxical inhibitory effect of bacteriostatic antibiotics on key mediators of mammalian innate immunity. When growth of species including Escherichia coli and Staphylococcus aureus is suppressed by chloramphenicol or erythromycin, the susceptibility of the bacteria to cathelicidin antimicrobial peptides or serum complement was markedly diminished. Survival of the bacteria in human whole blood, human wound fluid, or a mouse wound infection model was in turn increased after antibiotic-induced bacteriostasis. These findings provide a further rationale against the indiscriminate use of antibiotics.
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0687, USA.
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Kristian
authors.forename: Anjuli M
authors.initials: AM
authors.lastname: Timmer
authors.forename: George Y
authors.initials: GY
authors.lastname: Liu
authors.forename: Xavier
authors.initials: X
authors.lastname: Lauth
authors.forename: Neta
authors.initials: N
authors.lastname: Sal-Man
authors.forename: Yosef
authors.initials: Y
authors.lastname: Rosenfeld
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology; D054804:Cathelicidins; D002701:Chloramphenicol / Q000494:pharmacology; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects*; D005260:Female; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D003169:Complement Inactivator Proteins; D004917:Erythromycin; D002701:Chloramphenicol