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 <i>M. tuberculosis</i> (<i>Mtb</i>). With the increasing prevalence of multidrug and extensively drug resistant (MDR and XDR) TB, there is a need to study the mechanisms of <i>Mtb</i> survival in patients’ alveolar macrophages. The <i>Mtb</i> 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 <i>Mtb</i> 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 <i>ex vivo</i> culture for 16-18 hours and found its significant variations in <i>Mtb</i> 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 <i>Mtb</i> width did not change significantly. The <i>Mtb</i> ovoid and classical rods were observed simultaneously in the same <i>ex vivo</i> 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 <i>Mtb</i> 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 <i>Mtb</i> populations during persistence in TB patients’ lungs and the specific features of MDR- and XDR-TB disease.