Abstract
The type III secretion system (T3SS) is a conserved virulence factor used by many Gram-negative pathogenic bacteria and has become an important target for anti-virulence drugs. Most T3SS inhibitors to date have been discovered using in vitro screening assays. Pharmacokinetics and other important characteristics of pharmaceuticals cannot be determined with in vitro assays alone. In vivo assays are required to study pathogens in their natural environment and are an important step in the development of new drugs and vaccines. Animal models are also required to understand whether T3SS inhibition will enable the host to clear the infection. This review covers selected animal models (mouse, rat, guinea pig, rabbit, cat, dog, pig, cattle, primates, chicken, zebrafish, nematode, wax moth, flea, fly, and amoeba), where T3SS activity and infectivity have been studied in relation to specific pathogens (Escherichia coli, Salmonella spp., Pseudomonas spp., Shigella spp., Bordetella spp., Vibrio spp., Chlamydia spp., and Yersinia spp.). These assays may be appropriate for those researching T3SS inhibition.
Highlights
Antibiotics have revolutionized how the medical community treats bacterial infections and have contributed to the overall increase in life expectancy throughout the world [1]
The type III secretion system (T3SS) is a virulence factor commonly used by pathogenic Gram-negative bacteria [4,5,6]
Efforts have gone into screening for T3SS inhibitors, and a common theme among them is a lack of toxicity to the pathogen [22,32,33]
Summary
Antibiotics have revolutionized how the medical community treats bacterial infections and have contributed to the overall increase in life expectancy throughout the world [1]. The needle spans the bacterial membranes and the host cell membrane, allowing for direct secretion from the pathogen into the host. These secreted effector proteins reprogram the host’s machinery to allow for colonization. In addition to reprograming host machinery (Salmonella spp., Shigella spp.) [18,19], some effectors kill the target cells (Yersinia spp., Pseudomonas spp.) [20,21]. Efforts have gone into screening for T3SS inhibitors, and a common theme among them is a lack of toxicity to the pathogen [22,32,33] This is an important feature of these inhibitors, because it means they do not exert selective pressure.
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