Mycobacterium tuberculosis shape and size variations in alveolar macrophages of tuberculosis patients

Tuberculosis (TB) is a significant global health threat, with one-third of the world’s population infected with causative agent M. tuberculosis (Mtb). With the increasing prevalence of multidrug and extensively drug resistant (MDR and XDR) TB, there is a need to study the mechanisms of Mtb survival in patients’ alveolar macrophages. The Mtb shape and size alterations during TB disease are expected to be as the markers of virulence, specific defense against host responses and the peculiarities of microbe’s pathogenesis in individual patients. We estimated Mtb shape and size in alveolar macrophages isolated from the resected lungs of patients with pulmonary MDR- and XDR-TB (Ufimtseva, E. et al. Tuberculosis 2019; 114:77-90) after ex vivo culture for 16-18 hours and found its significant variations in Mtb as single and in colonies, including with cord morphology. Mycobacterial shape within alveolar macrophages varied from shorter oval, approximately 0.5 to 1 µm in length, to the classical rods with a mean length in 2-4 µm, and long filamentous forms over 6-7 µm in length, while Mtb width did not change significantly. The Mtb ovoid and classical rods were observed simultaneously in the same ex vivo cell cultures of patients with MDR- and XDR-TB, but often in the different alveolar macrophages, probably reflected some environmental fluctuations in patients’ lungs. The presence of filamentous Mtb was associated with increased virulence of pathogen from the lungs of these patients in guinea pig TB model. Thus, the shape and size variations demonstrated pleomorphic phenomena in Mtb populations during persistence in TB patients’ lungs and the specific features of MDR- and XDR-TB disease.