Tuberculosis, which is caused by Mycobacterium tuberculosis , is one of the world's deadliest diseases. We lack a clear understanding of how M. tuberculosis and related mycobacterial species cause disease. In the 1950's, it was reported that treating M. tuberculosis infected animals with tyloxapol improved the survival and in some cases protected the animals from death. Tyloxapol is a detergent that is commonly added to mycobacterial cultures to promote dispersed growth in the laboratory. Later studies suggested that tyloxapol altered the interaction between M. tuberculosis and the phagosomal membrane during macrophage infection. The ability to escape the phagosome is essential for mycobacteria to cause disease, and is mediated by a Type VII protein secretion system, ESX-1. Using M. marinum , a well-established model for understanding the molecular mechanisms of ESX-1 secretion, we show that tyloxapol used at more than 100-fold less than what is commonly used to grow mycobacteria in the lab, inhibits ESX-1 secretion. Our findings have widespread implications on how we interpret our findings as a field, and may explain why tyloxapol impacted M. tuberculosis infection of both animals and macrophages. Our study also indicates that tyloxapol can be used as a tool to understand the molecular mechanisms of ESX-1 protein secretion.
Collars et al. (Mon,) studied this question.