Escherichia coli adenylate cyclase at

Comments: 2018

MBio. 2018
Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic Escherichia coli
Molina-Quiroz RC, Silva-Valenzuela C, Brewster J, Castro-Nallar E, Levy SB, Camilli A

Contrary to the authors’ conclusion that the poor growth of the cyaA strain "cannot explain the large increase in persister formation, since ampicillin kills growing bacteria, while metabolically dormant persister cells are spared ", growth rate may actually be a significant factor.  A laboratory cyaA strain of Escherichia coli is indeed known to exhibit a large reduction in growth rate.  During exponential growth, cyaA (and crp) mutants are small rod shaped but smaller than wild type, lateral wall elongation is however normal and, during aerobic growth, metabolism is not significantly altered.  Their size is in fact appropriate for their reduced growth rate (D'Ari R, 1988).  One may construe growth rate may be the major difference between wild type and cyaA strains in media supporting growth, and because there is preceding work indicating β-lactam bactericidal antibiotics can become bacteriostatic upon extension of the generation time (for example Cozens RM, 1986 or Tuomanen E, 1986), the above hasty conclusion should be re-assessed.

The statement "addition of exogenous cAMP did not restore WT killing kinetics to the Δcrp mutant (Fig. 1c), as would be expected if cAMP were acting through its receptor, CRP" may be questioned for its relevance, as Escherichia coli laboratory strains lacking CRP (also referred to as CAP) are known for producing large amounts of cAMP (Potter K, 1974; CRP-dependent activation of adenylate cyclase).

Perhaps most importantly, the present proposal may not agree with data indicating increase sensitivity to oxidative stress correlates with a higher level of persistence (Hryckowian AJ, 2013 with Leatham-Jensen MP, 2016).  In other words, if cyaA mutants have "an increased ability to cope with oxidative damage", they should also be less persistent.

This comment by M. Crasnier-Mednansky (martine [at] minst [dot] org) was originally posted on February 5, 2018 at PubMed Commons