Sarkar Paramita, Switzer Amy, Peters Christine, Pogliano Joe, Wigneshweraraj Sivaramesh
MRC Centre for Molecular Bateriology and Infection, Imperial College London, London SW7 2AZ, UK.
Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Nucleic Acids Res. 2017 Nov 2;45(19):11131-11143. doi: 10.1093/nar/gkx733.
Many bacterial adaptive responses to changes in growth conditions due to biotic and abiotic factors involve reprogramming of gene expression at the transcription level. The bacterial RNA polymerase (RNAP), which catalyzes transcription, can thus be considered as the major mediator of cellular adaptive strategies. But how do bacteria respond if a stress factor directly compromises the activity of the RNAP? We used a phage-derived small protein to specifically perturb bacterial RNAP activity in exponentially growing Escherichia coli. Using cytological profiling, tracking RNAP behavior at single-molecule level and transcriptome analysis, we reveal that adaptation to conditions that directly perturb bacterial RNAP performance can result in a biphasic growth behavior and thereby confer the 'adapted' bacterial cells an enhanced ability to tolerate diverse antibacterial stresses. The results imply that while synthetic transcriptional rewiring may confer bacteria with the intended desirable properties, such approaches may also collaterally allow them to acquire undesirable traits.
许多细菌因生物和非生物因素导致生长条件变化而产生的适应性反应，涉及转录水平上基因表达的重新编程。催化转录的细菌RNA聚合酶（RNAP）因此可被视为细胞适应性策略的主要调节因子。但是，如果应激因素直接损害RNAP的活性，细菌会如何反应呢？我们使用一种噬菌体衍生的小蛋白，在指数生长的大肠杆菌中特异性干扰细菌RNAP的活性。通过细胞学分析、在单分子水平追踪RNAP行为以及转录组分析，我们发现，适应直接干扰细菌RNAP性能的条件可导致双相生长行为，从而赋予“适应”的细菌细胞更强的耐受多种抗菌应激的能力。结果表明，虽然合成转录重排可能赋予细菌预期的理想特性，但这种方法也可能附带地使它们获得不良性状。
