Department of Microbiology and Cell Biology , Indian Institute of Science , Bengaluru , Karnataka , India.
ACS Chem Biol. 2018 Jun 15;13(6):1447-1454. doi: 10.1021/acschembio.8b00080. Epub 2018 May 18.
Diadenosine polyphosphates, ApA, which contain two adenosines in a 5',5' linkage through phosphodiester bonds involving 2-7 phosphates, regulate diverse cellular functions in all organisms, from bacteria to humans, under normal and stress conditions. We had earlier reported consistent occurrence of asymmetric constriction during division (ACD) in 20-30% of dividing mycobacterial cells in culture, irrespective of different growth media, implying exogenous action of some factor of mycobacterial origin. Consistent with this premise, concentrated culture supernatant (CCS), but not the equivalent volume-wise concentrated unused medium, dramatically enhanced the ACD proportion to 70-90%. Mass spectrometry and biochemical analyses of the bioactive fraction from CCS revealed the ACD-effecting factor to be ApA. Synthetic ApA showed a mass spectrometry profile, biochemical characteristics, and bioactivity identical to native ApA in the CCS. Thus, the present work reveals a novel role for ApA in generating cell-length asymmetry during mycobacterial cell-division and thereby cell-length heterogeneity in the population.
双腺苷多磷酸，ApA，由通过涉及 2-7 个磷酸酯键的 5'，5' 连接的两个腺苷组成，在正常和应激条件下，调节所有生物体（从细菌到人类）的多种细胞功能。我们之前曾报道过，在培养中的 20-30%的分裂分枝杆菌细胞中，存在一致的不对称收缩（ACD），这与不同的生长培养基无关，这意味着分枝杆菌来源的某些因子的外源性作用。与这一前提一致的是，浓缩培养上清液（CCS），而不是等效体积的浓缩未使用的培养基，极大地提高了 ACD 的比例，达到 70-90%。CCS 中生物活性部分的质谱分析和生化分析表明，ACD 效应因子是 ApA。合成 ApA 显示出与 CCS 中天然 ApA 相同的质谱图谱、生化特性和生物活性。因此，本研究揭示了 ApA 在分枝杆菌细胞分裂过程中产生细胞长度不对称性以及由此产生的群体中细胞长度异质性方面的新作用。
