Understanding factors contributing to bacterial burden in granulomas of Mycobacterium tuberculosis-infected monkeys

Mycobacterium tuberculosis (Mtb) is the bacterium that causes tuberculosis (TB) and kills more people per year than any other infectious agent. Factors that influence the spread of Mtb within individuals are an ongoing topic of investigation. We analyzed novel data from 25 Mtb-infected rhesus macaques on the number of colony forming units (CFUs) in individual granulomas in lungs of the animal. In these experiments, macaques were infected with different initial doses (varying between 1-40 CFUs); animals underwent different Mtb-controlling treatments, and measurement of lung granuloma CFUs were done at different time points after the infection. We found that a higher initial dose resulted in a larger average number of CFUs per granuloma when comparing macaques given an initial dose of 8 or 40 CFUs. The caveat in this comparison, however, is that time since infection and controlling treatments were varied between the doses. Interestingly, we found that variability in CFU/granuloma (estimated using coefficient of variation, CV) is higher among all animals as compared to CV estimated for individual animals. This suggests that infection dynamics in granulomas of a given animal proceeds more similarly than infection between two randomly chosen granulomas in two different animals. This result challenges the commonly stated hypothesis that dynamics of Mtb in individual granulomas in one animal are independent. Our analysis also suggested that the CFU/granuloma in macaques is dependent on a combination of the initial dose of Mtb, treatment, and time since infection. These results lead further research into assessing the relative contributions the dose and time since infection have on TB infection in the lungs of the macaque and is the focus of ongoing research.