Group B streptococci exposed to rifampin or clindamycin (versus ampicillin or cefotaxime) stimulate reduced production of inflammatory mediators by murine macrophages.
Streptococcus agalactiae (group B Streptococcus, GBS) is an important cause of sepsis and meningitis in neonates, and excessive production of the inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO) causes tissue injury during severe infections. We hypothesized that exposure of GBS to different antimicrobial agents would affect the magnitude of the macrophage inflammatory response to this organism. We stimulated RAW 264.7 murine macrophages with a type-Ia GBS isolate in the presence of ampicillin, cefotaxime, rifampin, clindamycin, or gentamicin, singly or in combination. We found that GBS exposed to rifampin or clindamycin (versus beta-lactam antibiotics) stimulated less TNF secretion and inducible nitric oxide synthase (iNOS) protein accumulation in RAW 264.7 cells. Furthermore, GBS exposed to combinations of antibiotics that included a protein synthesis inhibitor stimulated less macrophage TNF and iNOS production than did organisms exposed to beta-lactam antibiotics singly or in combination. We conclude that exposure of GBS to rifampin or clindamycin leads to a less pronounced macrophage inflammatory mediator response than does exposure of the organism to cell wall-active antibiotics.
Brinkmann
Kevin C
KC
Department of Pediatrics, University of Tennessee Health Science Center, Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, 38103, USA. kevinbrinkmann@comcast.net
Talati
Ajay J
AJ
Akbari
Raumina E
RE
Meals
Elizabeth A
EA
English
B Keith
BK
D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology; D002460:Cell Line; D002981:Clindamycin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012293:Rifampin / Q000494:pharmacology*; D013292:Streptococcus agalactiae / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002981:Clindamycin; D000667:Ampicillin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D002439:Cefotaxime; D012293:Rifampin