Khaova E.A., Kashevarova N.M., Tkachenko A.G
REGULATION OF BACTERIAL PERSISTENCE BY POLYAMINES THROUGH THE STIMULATION OF EXPRESSION OF RPOS, YQJD AND RMF GENES ^{[№ 9 ' 2017]}
Persisters are rare dormant variants of regular cells and are highly tolerant to antibiotics. Persisters are able to resume growth. These observations suggest that persister cells may be the main culprit responsible for the recalcitrance of chronic infectious disease to antimicrobial therapy. General stress responses and polyamines are described to responsible for the formation of persister cells.
Showed that polyamines putrescine, spermidine and cadaverine upregulate the formation of Escherichia coli persister cells in a dynamic fashion through the stimulation of expression of rpoS, yqjD and rmf genes, relating to general stress responses. Results showed that rpoS gene is the most upregulated by spermidine. The expression of yqjD gene is slightly dependent on polyamines. We obtained that the expression of yqjD is dependent on rpoS. These results are in agreement with previously published data. So, although yqjD is not referred to as a “polyamine modulon”, polyamines still can upregulate its expression indirectly through positive effects on rpoS expression. The persister cells frequency of knockout strains decreased versus their parent during the time periods of stationary phase that were specific for each gene knockout mutant. The persister cell frequency of ΔrpoS strain exhibited maximal decrease versus parental strain at early stationary phase. Therefore, the persister formation at early stationary phase is primarily dependent on rpoS gene. The persister cell frequencies of rmf and yqjD mutants decreased nearer to the lowest values versus parent at late stationary phase. These results show that rmf and yqjD genes can significantly contribute to the persister formation at late stationary phase. These data are confirmed by results, obtained with strains harboring double and triple knockout mutations.
Therefore, rpoS gene is the most upregulated by spermidine and is involved in the persister cell formation predominating at early stationary phase. rmf gene, also relating to polyamine modulon, and yqjD gene, whose expression is slightly dependent on polyamines, are involved in the persister cell formation predominating at late stationary phase.