Effect of imipenem on monoclonal antibody-mediated protection against Escherichia coli O18K5.
Flow cytometry revealed that the binding of immunoglobulin M monoclonal antibodies (MAbs) to Escherichia coli O18K5 was modulated by exposure of the bacteria to subinhibitory concentrations of imipenem. The binding of anti-K5 MAb was decreased, while the binding of anti-O18 MAb was increased. In addition, anti-lipid A MAbs bound only to imipenem-treated bacteria. The biological effect of MAb binding was investigated in BALB/c mice by determination of the levels of bacteremia, tumor necrosis factor (TNF) in serum and survival after intraperitoneal challenge with bacteria preincubated with MAb. Neither MAb alone (150 micrograms per animal) proved to be protective against untreated bacteria. Anti-lipid A MAb on its own, in contrast to anti-K5 and anti-O18 MAbs, was not protective against imipenem-treated bacteria. Only combinations which included anti-O18 MAb and anti-K5 MAb exerted in mice enhanced protection against smooth E. coli O18K5 as well as imipenem-treated E. coli O18K5. This was reflected by reduced TNF levels in serum and increased survival. The addition of anti-lipid A MAb to the combination of anti-K5 MAb and anti-O18 MAb reduced serum TNF levels in mice, but not significantly.
Frasa
H
H
Eijkman-Winkler Institute for Medical Microbiology, University Hospital, Utrecht, The Netherlands.
Benaissa-Trouw
B
B
Tavares
L
L
van Kessel
K
K
Hustinx
W
W
Schellekens
J
J
Kraaijeveld
K
K
Verhoef
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D016470:Bacteremia / Q000517:prevention & control*; D004926:Escherichia coli / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016998:Helicobacter; D015378:Imipenem / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013845:Thienamycins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D013845:Thienamycins; D015378:Imipenem