Reply to Nikaido: The pyruvate cycle provides respiratory energy and potentiates aminoglycosides to kill multidrug-resistant bacteria

Abstract

Nikaido (1) claims, contrary to our work (2), that the P cycle is not a general mechanism for energy production and that it does not sensitize bacteria toward aminoglycosides. However, the argumentation for both points is not convincing to us. The P cycle is proposed from the stable-isotope–based nontargeted isotope fate detection analysis, in which we found labeled glutamate flux to glucogenesis and identified three additional steps—transforming oxaloacetate (OAA) to citrate through phosphoenolpyruvate (PEP), pyruvate, and acetyl-CoA—to finish the metabolic process. The finding was further supported by 13C-labeled glucose in figure 7G of ref. 2. The PEP-pyruvate-OAA node, also referred to as the anaplerotic node, is a main way … [↵][1]1To whom correspondence may be addressed. Email: pengb26{at}sysu.edu.cn or pxuanx{at}sysu.edu.cn. [1]: #xref-corresp-1-1