Differential antibacterial activity of genistein arising from global inhibition of DNA, RNA and protein synthesis in some bacterial strains

Abstract

Antibacterial activities of various flavonoids have been reported previously, but mechanism(s) of their action on bacterial cells remain(s) largely unknown. Here, we investigated effects of genistein, an isoflavone, and representatives of other flavonoids: daidzein (another isoflavone), apigenin (a flavone), naringenin (a flavanone) and kaempferol (a flavonol), on commonly used laboratory strains of model bacterial species: Escherichia coli, Vibrio harveyi and Bacillus subtilis. We found that E. coli was resistant to all tested flavonoids at concentrations up to 0.1 mM, while high sensitivity of V. harveyi to most of them (except daidzein, which exhibited significantly less pronounced effect) was observed. Effects of the flavonoids on B. subtilis were relatively intermediate to the two extremes, i.e., E. coli and V. harveyi. Action of genistein on bacterial cells was investigated in more detail to indicate changed cell morphology (formation of filamentous cells) of V. harveyi and drastic inhibition of global synthesis of DNA and RNA as shortly as 15 min after addition of this isoflavone to a bacterial culture to a final concentration of 0.1 mM. Protein synthesis inhibition was also apparent, but delayed. Both cell morphology and synthesis of nucleic acids and proteins were unaffected in E. coli cultures under analogous conditions. Studies on cell survival suggest that genistein is a bacteriostatic agent rather than a bactericidal compound.

Assessment of antibacterial effects of flavonoids by estimation of generation times in liquid bacterial cultures

“…The individual bacteria revealed various degrees of sensitivity to different flavonoids. Growth rate of B. subtilis was decreased about two times in the presence of 100 µM genistein, apigenin or kaempferol, but daidzein and naringenin had no significant influence (Table 1), which generally agrees with previously published results (Oksuz et al 1984;Bashir et al 1994;Aljancic et al 1999;Ulanowska et al, 2006). Growth of cultures of M. luteus was completely inhibited by 100 µM kaempferol or naringenin, which was similar to the phenotype of Sarcina sp., revealing high sensitivity to kaempferol but only partial sensitivity to naringenin (Table 1).…”

“…As noted previously (Ulanowska et al 2006), V. harveyi is highly sensitive to most flavonoids; among compounds tested, only daidzein did not cause a strong growth inhibition of this bacterium (Table 1). In contrast to V. harveyi, growth of C. freundii, E. coli, K. pneumoniae, P. vulgaris, S. enterica and S. marcescens was unaffected or only slightly affected by all tested compounds (Table 1).…”

“…Therefore, it is evident that this method gives quantitative results that can be directly compared with results obtained in various laboratories. In fact, monitoring of growth of microbial cultures was successfully employed in studies on activities of isoflavones previously (Parniske et al 1991;Yazdanyar et al 2001;Ulanowska et al 2006), but those authors used this method for specific purposes of studies on mechanisms of actions of these compounds rather than for screening of their effects on various microorganisms.…”

The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1

“…Although all these molecules are structurally similar, the selected flavanones (eriodictyol, naringenin, taxifolin) demonstrated a strong QS-inhibition activity, while, at the same concentration, the three flavonols (kaempferol, myricetin, quercetin) and the two flavones (apigenin, luteolin) showed no QS modulation, but a bactericidal or bacteriostatic activity, as already reported for other bacteria (Ulanowska et al, 2006;Xu & Lee, 2001). This highlights the possible involvement of the hydroxyl substitutions and/or the double bond in the central pyran Cring in the opposing activities (bacteriostatic/bactericidal versus anti-QS) of these flavonoids.…”

Excess Production ofBacillus subtilisQuercetin 2,3-Dioxygenase Affects Cell Viability in the Presence of Quercetin

“…1) In addition to nutrient materials, plant cells exude flavonoids, and hence, bacteria in the rhizosphere are exposed to considerable amounts of various flavonoids. Certain flavonoids possess antibacterial activity, 2) and quercetin inhibits bacterial DNA gyrase, which induces DNA cleavage. 3) To avoid harmful effects, certain bacteria are equipped with a degradation system for flavonoids for detoxification.…”