Aversion Therapy for Bacteria: Repurposing Aurodox

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Antibiotics have been used for many years and are central to the treatment of many common bacterial infections. However, because antibiotics kill bacteria, there is a strong selection for mutants, slightly different from the parental type of bacteria, which are not killed: a new resistant form. These resistant cases of bacteria that are no longer susceptible to common antibiotics means that there is a great need for new alternative forms of treatment. Of all the bacteria that causes problems, the gram negative family are the hardest treat because they rapidly develop resistance. One possibility is to render the disease-causing bacteria less dangerous by turning off their offensive weapons. Compounds that "turn off' bacterial weapons are called "anti-virulence" compounds because they don't try to kill the bug, they just render them less dangerous. Imagine taking an army and removing all its key weapons- it's a lot less effective. Using anti-virulence factors is attractive for the following reasons:(1) Anti-virulence compounds "disarm" bacteria rather than killing them, generating less selection for resistant mutants.(2) Secondary infections associated with antibiotic treatment such as those caused by Clostridium difficile and Candida albicans should also be dramatically reduced as natural "good" bacteria are not wiped out during treatment. (3) For toxin-producing bacteria treatment with traditional antibiotics is controversial, with some reports of increased release of toxins and more severe symptoms. By not killing the bacteria, toxin release is avoided.My lab has been developing and testing new anti-virulence compounds and working out how they function. We "re-discovered" a compound that is safe for animals, called aurodox which was actually found in the early 1970s from other bacteria that live in the soil. When we use aurodox with bacteria that cause serious diseases, specifically the infamous "burger bug" "E. coli O157" we are able to switch off the major weapon the bacteria use to attach to host cells. In effect we are just switching off the anchor used to attach to the gut, which should ensure the bacteria are simply flushed out of the body. In this work we want to show that aurodox can prevent or treat disease and also work out exactly how it works. We also want to see if aurodox has any negative effects on the "good" bacteria in our guts. Answering these questions would pave the way to use aurodox as the first treatment against EHEC and, more widely, show that anti-virulence approaches are a viable alternative to traditional antibiotics.