Antivirulence Therapy for Animal Production: Filling an Arsenal with Novel Weapons for Sustainable Disease Control

Antibiotics are still critically important as a first line therapy for the treatment of various bacterial infections in the clinic. In addition to their use in human medicine, these compounds have also been used for decades in animal production, for both growth promotion and veterinary purposes [1,2]. Because of the development and spread of antibiotic resistance, there is a growing awareness that antibiotics should be used with more care [3], and as a consequence, the development of alternative methods to control pathogenic bacteria in animal production will be important to ensure good productivity in the future. Infection of both terrestrial and aquatic animals by bacterial pathogens requires the production of different virulence factors, i.e. gene products that allow the pathogenic bacteria to enter and damage the host. Major virulence factors include gene products involved in motility, adhesion, host tissue degradation, iron acquisition, secretion of toxins, and protection from host defense [4]. As virulence factors are required for infection, preventing pathogens from producing them constitutes an interesting alternative strategy for disease control, a strategy that has been termed antivirulence therapy [5]. Antivirulence therapy is based on a thorough understanding of the mechanisms by which bacterial pathogens cause disease. In this respect, studies aimed at understanding how bacteria cause disease have identified (and will probably continue to do so) targets for therapeutics with completely novel modes of action. Inhibitors of specific virulence factors, such as secretion systems, have been reported in literature [6]. However, considerably more research effort is being directed towards interference with regulatory mechanisms that control the expression of (multiple) virulence factors, such as bacterial cell-tocell communication (quorum sensing) and host-pathogen signalling (Fig. 1). The following paragraphs will focus on interference with these mechanisms as a novel strategy to control animal pathogens, using Escherichia coli and Salmonella spp. as examples of pathogens for terrestrial animals, and Aeromonas spp. and Vibrio spp. as examples of aquatic pathogens.