How does Mtb mediate cough and transmission?

The success of any bacterial pathogen ultimately depends on its ability to multiply and infect new hosts. Many pathogenic bacteria interact with hosts by secreting virulence molecules like proteins and lipids. A classic example is the production of cholera toxin by Vibrio cholera, which enhances the pathogen’s spread from person-to-person by promoting profuse watery diarrhea. Mtb, one of the most successful pathogens in human history, also employs sophisticated means of dissemination, including mediating caseation, tissue destruction, and airborne transmission, to propagate the human disease tuberculosis. Yet, despite the massive toll of Mtb on world health, the molecular mechanisms responsible for Mtb transmission remain elusive. Cough is a primary symptom of active pulmonary tuberculosis and is known to be a critical mechanism of transmission. Although cough is a major route of aerosolization and spread of Mtb, very little is known about the molecular factors that produce cough during human infection. Thus, there is an urgent need to identify bacterial factors that induce cough. Because airway nociceptive neurons can trigger cough and some bacteria, including mycobacteria, secrete complex molecules targeting neurons, we hypothesized that Mtb secretes molecules triggering nociceptive neurons to activate the cough response thereby facilitating disease transmission.

Figure 5