Rodionov D G, Ishiguro E E
Department of Biochemistry and Microbiology, University of Victoria, British Columbia, Canada.
Microbiology (Reading). 1996 Oct;142 ( Pt 10):2871-7. doi: 10.1099/13500872-142-10-2871.
The role of phospholipid synthesis in peptidoglycan metabolism during growth of Escherichia coli was determined. The inhibition of phospholipid synthesis, achieved by inhibiting fatty acid synthesis with cerulenin or by glycerol deprivation of gpsA mutant strains, resulted in the concomitant inhibition of peptidoglycan synthesis. These effects on peptidoglycan synthesis were relatively specific in that the treatments did not cause a general inhibition of macromolecular synthesis. Furthermore, the inhibition of phospholipid synthesis also resulted in the rapid development of penicillin tolerance. It was unlikely that penicillin tolerance in these cases were simply due to the inhibition of growth caused by cerulenin treatment or glycerol deprivation because treatments with more effective growth inhibitors, e.g. chloramphenicol or norfloxacin, did not confer penicillin tolerance. Penicillin tolerance was shown to be a direct consequence of the inhibition of phospholipid synthesis and not due to the possible accumulation of guanosine-3',5'-bispyrophosphate (ppGpp), the starvation stress signal molecule known to be responsible for the development of penicillin tolerance in amino-acid-deprived bacteria. Therefore, peptidoglycan metabolism is coupled to phospholipid synthesis during growth of E. coli, and this may represent an important means to ensure the coordination of cell envelope synthesis in growing bacteria.
确定了磷脂合成在大肠杆菌生长过程中肽聚糖代谢中的作用。通过用浅蓝菌素抑制脂肪酸合成或通过剥夺 gpsA 突变株的甘油来抑制磷脂合成，会导致肽聚糖合成同时受到抑制。这些对肽聚糖合成的影响相对具有特异性，因为这些处理不会导致大分子合成的普遍抑制。此外，磷脂合成的抑制还导致青霉素耐受性迅速发展。在这些情况下，青霉素耐受性不太可能仅仅是由于浅蓝菌素处理或甘油剥夺导致的生长抑制，因为用更有效的生长抑制剂（如氯霉素或诺氟沙星）处理不会赋予青霉素耐受性。已证明青霉素耐受性是磷脂合成抑制的直接后果，而不是由于鸟苷 -3',5'-双焦磷酸 (ppGpp) 的可能积累，ppGpp 是已知在氨基酸缺乏的细菌中导致青霉素耐受性发展的饥饿应激信号分子。因此，在大肠杆菌生长过程中，肽聚糖代谢与磷脂合成相关联，这可能是确保生长中细菌细胞包膜合成协调的重要手段。
