Differential antibiotic-induced release of endotoxin from gram-negative bacteria

Abstract

Treatment of log phase cultures of Escherichia coli with cell wall active antibiotics results in increased exposure of immunologically reactive lipid A epitopes of lipopolysaccharide (LPS) and release of soluble LPS into culture supernatants. Comparison of the efficacy of two cell wall active antibiotics, ceftazidime, a penicillin-binding protein 3 selective antibiotic, and imipenem, a penicillin-binding protein 2 selective antibiotic, for their relative efficacy in mediating LPS release indicated quantitative but not qualitative differences, with the former antibiotic manifesting a significantly broader range of concentrations at which LPS release could be demonstrated. Comparison of the relative efficacy of these two antibiotics in a mouse bacteraemia model in which animals were made hypersensitive to the lethal effects of endotoxin by treatment with D-galactosamine indicated that the latter antibiotic may provide a greater level of protection. These studies suggest that the release of endotoxin mediated by antibiotic treatment may contribute to the pathogenesis of disease in infectious due to gram-negative organisms.

Modified Virulence of Antibiotic-Induced Burkholderia pseudomallei Filaments

“…Such enlargements were not seen in ofloxacin-or trimethoprim-induced filaments or untreated bacteria. Because increased levels of endotoxin production have been observed to be induced by both B. pseudomallei (31) and many other filamentous gram-negative bacteria (5,6,11,17) during antibiotic treatment for sepsis caused by gramnegative bacteria and because most of these antibiotics affect the bacterial cell wall through PBP 3, we think that the enlargement of the periplasmic space observed in ceftazidimeinduced filaments could be structural features resulting from increased levels of endotoxin production.…”

Clinical implications of antibiotic-induced endotoxin release in septic shock

“…A direct link between endotoxin release and TNFα-liberation from monocytes has also recently been demonstrated in different in vitro systems [61,25] Differences in the endotoxin-liberating potential of antibiotics An important step in understanding treatment-related endotoxin release was the finding that different classes of antimicrobial substances led to different levels of circulating endotoxin. Since then, many investigators have demonstrated both in vitro and in vivo that the use of certain antibiotics leads to significantly increased levels of free endotoxins while others produce relatively low amounts [16,62,63,64,65,66,67,68]. The amount of LPS, LOS, LTA or sPG is obviously dependent on the type and number of invading bacteria.…”

Escherichia coli high-cell-density culture: carbon mass balances and release of outer membrane components

“…For example, EDTA, tris-buffer, or saline promote OM release [7,25,22]. The presence of antibiotics [26], phage infection [6,27], increased temperature [28], and amino acid depletion [20] also enhance the release. However, LPS synthesis was shown to be regulated by the stringent control mechanism, and amino acid deprivation stimulated the rate of LPS release in relA mutants but not in relA + strains [21].…”