Effect of Epinephrine, Norepinephrine, and Estradiol on Persister Formation in the Cultures of Staphylococci from the Human Microbiota and Their Resistance to Starvation and New Medium Stresses

Effects of the human hormones and human microbiota on the growth of symbiotrophic and saprotrophic bacteria are well-known. However, no information is available on the effects of hormones on formation and survival of persister cells. Persistence is a phenotype providing the survival of the population in the presence of biocidal doses of antibiotics. Hence, the aim of this work was to investigate in vitro the effects of the human humoral regulation factors catecholamines (epinephrine (E) and norepinephrine (NE)) and the steroid hormone estradiol on the frequency of persisters’ (P) formation and their survival under abrupt changes of cultivation conditions—starvation with subsequent transfer of P into a fresh rich medium. This is the first study demonstrating E and NE to impact the growth of microorganisms that inhabit human skin, Staphylococcus aureus and S. epidermidis , as well as the frequency of formation of antibiotic-tolerant and lysing agents-resistant persister cells. The effect of E and NE depended on their concentration. New data were obtained on the effect of catecholamines and estradiol on survival of S. epidermidis P under drastic changes of incubation conditions. Under conditions of long-term (12 h) starvation in 0.9% NaCl, E and NE at both physiological (ph) concentrations (4.9 and 3.6 nM) and higher ones (10 ph and 100 ph) did not affect P survival; the P amounts in the control and experimental variants decreased by two orders of magnitude (from 10 8 to 10 6 CFU/mL). E had no effect on the rich medium stress, and caused the so-called substrate-accelerated cell death, while NE at all the tested concentrations induced transition of P to an uncultured state with subsequent resuscitation (return of the colony-forming ability). Estradiol in the physiological concentration (0.22 nM) had no effect on P survival under starvation, while higher doses (10 ph and 100 ph) reduced starvation stress in P, and the amount of P decreased only 2 times. Higher estradiol concentrations (10 ph and 100 ph) alleviated the rich medium stress. Data were obtained concerning the effect of human humoral regulation factors on: (1) frequency of P formation in the cultures of S. aureus and S. epidermidis ; (2) P survival under starvation; and (3) their reversion to growth in fresh medium, i.e., under conditions closer to that in the human organism.