Impairment of innate immune killing mechanisms by bacteriostatic antibiotics.
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.
Kristian
Sascha A
SA
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0687, USA.
Timmer
Anjuli M
AM
Liu
George Y
GY
Lauth
Xavier
X
Sal-Man
Neta
N
Rosenfeld
Yosef
Y
Shai
Yechiel
Y
Gallo
Richard L
RL
Nizet
Victor
V
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*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D003169:Complement Inactivator Proteins; D004917:Erythromycin; D002701:Chloramphenicol