Submitted to: Antimicrobial Agents and Chemotherapy
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/2/2008
Publication Date: 5/12/2008
Citation: Sallum, U.W., Chen, T.T. 2008. Inducible Resistance of Fish Bacterial Pathogens to the Antimicrobial Peptide Cecropin B. Antimicrobial Agents and Chemotherapy. 52(9):3006-3012. Interpretive Summary: While antibiotics have been shown to be effective in controlling many species of pathogenic microorganisms, a major drawback is the development of resistant microorganisms. Since naturally occurring antimicrobial peptides could be considered as antibiotics, it is important to address whether resistant microorganisms could be developed when exposed to antimicrobial peptides for a long period of time. We determined that resistant microorganisms could develop by treating known fish bacterial pathogens with high dose of cecropin, a natural occurring antimicrobial peptide, for many generations. When the selection pressure of cecropin is removed, the bacterial pathogens return to the original sensitivity to cecropin. These results indicate that antimicrobial peptides will not cause fish pathogens to become genetically resistant to these compounds even after prolonged use. Therefore, antimicrobial peptides are excellent candidates for developing an efficient, safe and environmentally friendly means of controlling fish pathogens in aquaculture operation.
Technical Abstract: Cecropin B is a cationic antimicrobial peptide originally isolated from the diapausing pupae of the giant silk moth, Hylphora cecropia. Cecropin B elicits its antimicrobial effects through disruption of the anionic cell membranes of gram-negative bacteria. Previous work by our laboratory demonstrated that a constitutively expressed cecropin B transgene conferred enhanced resistance to bacterial infection in medaka. The development of antibiotic resistance by pathogenic bacteria is a growing problem. The potential for fish bacterial pathogens to develop resistance to cecropin B was addressed in this study. Four fish bacterial pathogens were selected for the study based on their importance in aquaculture. Vibrio anguillarum, Vibrio vulnificus, and Yersinia ruckeri all exhibited inducible resistance to cecropin B. The inducible resistance of these three pathogens was correlated with reversible changes in their ultrastructures, as observed by scanning electron microscopy. V. anguillarum was demonstrated to become more adhesive to a CHSE-214 cell monolayer and to cause increased cumulative mortality in medaka following exposure to cecropin B. This work demonstrates that the resistance of fish bacterial pathogens to cecropin B is inducible and suggests that resistance to other cationic antimicrobial peptides may occur through similar means. The observed changes in ultrastructure and infectivity suggest that resistance to antimicrobial peptides is an integral part of the pathogenesis of fish gram-negative bacterial pathogens.