RT Journal Article
SR Electronic
T1 Mycobacterial small noncoding RNAs MTS0997 and MTS1338 are novel virulence factors of M. tuberculosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2465
DO 10.1183/13993003.congress-2021.PA2465
VO 58
IS suppl 65
A1 Galina Shepelkova
A1 Vladimir Evstifeev
A1 Ilya Sivokozov
A1 Tatiana Azhikina
A1 Atadzhan Ergeshov
A1 Vladimir Yeremeev
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/PA2465.abstract
AB Introduction: Small RNAs of intracellular pathogenic bacteria not only adapt the bacterial transcript to changing environmental conditions, but also interact with the transcriptome of the infected organism, thereby interfering with the antibacterial defense.Aims and objectives: We investigated the role of small RNAs of M. tuberculosis, MTS1338 and MTS0997, as regulators that trigger a cascade of reactions for damping macrophage (mph) damaging factors.Methods: Mycobacteria growth inhibition in vitro assay was used to assess Mph activity. Mph (human alveolar (AM) or peritoneal mouse) were co-cultured in vitro with M. tuberculosis H37Rv wt, ΔMTS1338, and ΔMTS0997. After 72 hours of incubation, the viability of Mtb was assessed by the selective inclusion of [3H]-Uracil. The expression level of cytokines/chemokines genes were analyzed by TaqMan PCR Assay.Results: Differences in the survival of wild-type, ∆MTS0997 and ∆MTS1338 M. tuberculosis were detected in AM. Growth of ΔMTS1338 is better restricted by AM than that of ∆ MTS0997. Activation of mouse peritoneal Mph infected with wild-type, ∆MTS0997 and ∆MTS1338 Mtb was evaluated by the level of cytokine expression. Differences were registered between all groups compared. Mph infection of wt and ΔMTS0997 leads to an increase in the expression of proinflammatory cytokines TNF, IL-11, IL-1β and NF-IL6. Infection with ∆MTS1338 mutant leads to a significantly greater increase in the expression of NF-IL6, Aif1, and MARCO.Conclusions: The deletion of MTS0997 and MTS1338 decreases bacterial “virulence”. Mutants are more efficient in Mphs activation and are more readily cleared by Mphs as compared with wt strain.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2465.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).