Tubercle Bacilli in Lungs Resected from Tuberculosis Patients

Summers, James; Stanley, Arthur; Stringer, C J

doi:10.1056/nejm195409162511206

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following up these observations (Vijay et al, 2014a,b), in the present study, we tested whether the specific sub-populations of SCs and NCs bear differential susceptibility to antibiotic (rifampicin and isoniazid), oxidative (H 2 O 2 ), and nitrite (acidified NaNO 2 ) stress conditions to which both pathogenic and non-pathogenic mycobacteria are exposed both inside and outside infected cells, infected animals (Lenaerts et al, 2007; Hoff et al, 2011), TB patients (Smith, 1898; Forsyth, 1909; Summers et al, 1954; Hobby et al, 1973), and in the environment (Parashar et al, 2009; Velayati et al, 2015). For this purpose, the proportions of the SCs (formed from the highly-deviated ACD of normal/long-sized mother cells and SCDs of short-sized mother cells) and of the NCs in the MLP population of M. smegmatis and M. tuberculosis cultures, and their growth rate post-division from highly-deviated ACD of NCs and the SCD of SCs, were first determined.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterial Cultures Contain Cell Size and Density Specific Sub-populations of Cells with Significant Differential Susceptibility to Antibiotics, Oxidative and Nitrite Stress

et al. 2017

View full text Add to dashboard Cite

The present study shows the existence of two specific sub-populations of Mycobacterium smegmatis and Mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (MLP) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. One of these sub-populations (~10% of the total population), contained short-sized cells (SCs) generated through highly-deviated asymmetric cell division (ACD) of normal/long-sized mother cells and symmetric cell divisions (SCD) of short-sized mother cells. The other sub-population (~90% of the total population) contained normal/long-sized cells (NCs). The SCs were acid-fast stainable and heat-susceptible, and contained high density of membrane vesicles (MVs, known to be lipid-rich) on their surface, while the NCs possessed negligible density of MVs on the surface, as revealed by scanning and transmission electron microscopy. Percoll density gradient fractionation of MLP cultures showed the SCs-enriched fraction (SCF) at lower density (probably indicating lipid-richness) and the NCs-enriched fraction (NCF) at higher density of percoll fractions. While live cell imaging showed that the SCs and the NCs could grow and divide to form colony on agarose pads, the SCF, and NCF cells could independently regenerate MLP populations in liquid and solid media, indicating their full genomic content and population regeneration potential. CFU based assays showed the SCF cells to be significantly more susceptible than NCF cells to a range of concentrations of rifampicin and isoniazid (antibiotic stress), H2O2 (oxidative stress),and acidified NaNO2 (nitrite stress). Live cell imaging showed significantly higher susceptibility of the SCs of SC-NC sister daughter cell pairs, formed from highly-deviated ACD of normal/long-sized mother cells, to rifampicin and H2O2, as compared to the sister daughter NCs, irrespective of their comparable growth rates. The SC-SC sister daughter cell pairs, formed from the SCDs of short-sized mother cells and having comparable growth rates, always showed comparable stress-susceptibility. These observations and the presence of M. tuberculosis SCs and NCs in pulmonary tuberculosis patients' sputum earlier reported by us imply a physiological role for the SCs and the NCs under the stress conditions. The plausible reasons for the higher stress susceptibility of SCs and lower stress susceptibility of NCs are discussed.

show abstract