CidA and LrgA: a “Hole” Lot More than Programmed Cell Death

What do programmed cell death (PCD) and carbohydrate metabolism by-product transport have in common? Intriguingly, both processes involve the cidABC and lrgAB operons in the major human pathogen Staphylococcus aureus. Previously, CidA and LrgA have been studied in the context of programmed cell death, but a second function in overflow metabolism is increasingly evident. New work from J. L. Endres, S. S. Chaudhari, X. Zhang, J. Prahlad, et al. (mBio 13:e02827-21, 2022, https://doi.org/10.1128/mBio.02827-21) combining a lysis cassette, mutagenesis, and classic microbiology demonstrates that CidA and LrgA function as holins to support endolysin-induced lysis. But that’s not all—the lrgAB operon also facilitates pyruvate uptake during microaerobic and anaerobic growth. This commentary highlights the main findings from this work and places them in context of the literature to date. Finally, as these proteins are highly conserved and carry out disparate functions of great importance, it is tempting to speculate future work will elucidate the link between S. aureus lysis and pyruvate metabolism.