Induction of Escherichia coli and Vibrio cholerae enterotoxins by an inhibitor of protein synthesis

Abstract

Enterotoxigenic Escherichia coli or Vibrio cholerae 569B (Inaba) grown in the presence of the antibiotic lincomycin, an inhibitor of protein synthesis, produced elevated levels of heat-labile enterotoxin or choleragen, respectively, as assayed by both vascular permeability factor and capacity to elicit fluid accumulation in rabbit ileal loops. This induction of enterotoxin did not reflect either a coupling of lincomycin resistance with increased enterotoxigenicity or an effect of lincomycin on cellular release of enterotoxin, since spontaneously isolated lincomycin-resistant mutants ofboth E. coli and V. cholerae still required lincomycin for induction, and large increases in E. coli permeability factor activity were found intracellularly as well as extracellularly. After the period of exponential growth, E. coli became refractory to induction by lincomycin, although most of the induced enterotoxin activity appeared only after this period. No increase in copy number of the enterotoxin plasmid in E. coli 711 (P307) was found in induced cells by analysis of deoxyribonucleic acid reassociation kinetics. These and other data suggest that synthesis of enterotoxin, or at least its accumulation, is normally limited by cellular factors whose synthesis is preferentially inhibited by lincomycin. A possible connection between this phenomenon and lincomycinassociated diarrhea is considered.

Stimulation by lincomycin of production of cholera-like enterotoxin in Vibrio cholerae non-O1

“…It is clear, however, that toxin production in these strains is not proportional to bacterial mass, either in the presence or absence of lincomycin. Variation in the amount of increase of enterotoxin production induced by lincomycin was also reported for the LT of enterotoxinogenic E. coli [1]. The reason for this variation may become apparent after the mechanism of stimulation of enterotoxin production by lincomycin is elucidated.…”

“…It has been reported that lincomycin, an inhibitor of protein synthesis, stimulates the production of cholera enterotoxin (CT) and Escherichia coli heat-labile enterotoxin (LT) [1][2][3]. Lincomycin causes an increase in the rate of synthesis of CT and thus the amounts of both extracellular and intracellular CT were significantly increased [2].…”

Isolation and characterization of a cholera-related enterotoxin from Salmonella typhimurium

“…It is likely that previous workers were unsuccessful in purifying it because it is found intracellularly in relatively small amounts, and they did not exploit the affinity chromatographic properties of agarose in its isolation. It is conceivable that greater quantities can be isolated using lincomycin induction [20] and/or other cultural conditions. 241…”

Production of heat-labile Escherichia coli enterotoxin

“…Finally, it should be emphasized that only extracellular heat-labile enterotoxin was determined in this study. Other methods for obtaining a high yield of enterotoxin have been tested, such as induction by the DNA inhibitor mitomycin C [13] and by the protein inhibitor lincomycin [ 14 ]. The combination of such methods with efficient cultivation methods may result in greatly facilitated production ofE.…”