High‐level iron mitigates fusaricidin‐induced membrane damage and reduces membrane fluidity leading to enhanced drug resistance in Bacillus subtilis

Abstract

Fusaricidins are a class of cyclic lipopeptide antibiotics that have strong antifungal activities against plant pathogenic fungi and excellent bactericidal activities against Gram-positive bacteria. The mechanism through which fusaricidin exerts its action is not yet entirely clear. To investigate the mode of action of fusaricidin, we determined the physiological and transcriptional responses of Bacillus subtilis to fusaricidin treatment by using a systems-level approach. Our data show that fusaricidin rapidly induced the expression of σ(W) regulon and caused membrane damage in B. subtilis. We further demonstrated that ferric ions play multiple roles in the action of fusaricidin on B. subtilis. Iron deprivation blocked the formation of hydroxyl radical in the cells and significantly inhibited the bactericidal activity of fusaricidin. Conversely, high levels of iron (>2 mM) repressed the expression of BkdR regulon, resulting in a smaller cellular pool of branched-chain precursors for iso- and anteiso-branched fatty acids, which in turn led to a decrease in the proportion of branched-chain fatty acids in the membrane of B. subtilis. This change in membrane composition reduced its bilayer fluidity and increased its resistance to antimicrobial agents. In conclusion, our experiments uncovered some novel interactions and a synergism between cellular iron levels and drug resistance in Gram-positive bacteria.

TonB-Dependent Receptors Affect the Spontaneous Oxytetracycline Resistance Evolution in Aeromonas hydrophila

“…Iron is a key nutrient for bacterial growth, further the Gram-negative strains were dependent on the TonB-dependent transporters for their iron uptake process . Moreover, the previous study revealed that a high concentration of iron can reduce the damage of fusaricidin to the cell membrane and increase the drug resistance in Bacillus subtilis . Furthermore, the iron plays a significant role in the development of Pseudomonas aeruginosa biofilms, which also makes the strain resistant to antibiotics .…”

“…36 Moreover, the previous study revealed that a high concentration of iron can reduce the damage of fusaricidin to the cell membrane and increase the drug resistance in Bacillus subtilis. 37 Furthermore, the iron plays a significant role in the development of Pseudomonas aeruginosa biofilms, which also makes the strain resistant to antibiotics. 38 Therefore, the increased level of expression in iron-related proteins of bacteria can enhance the iron uptake and enhance bacterial resistance to antibiotics.…”

Antibacterial and Antibiofilm Activities of a Novel Synthetic Cyclic Lipopeptide against Cariogenic Streptococcus mutans UA159

“…Additionally, after 3 h, the genes involved in cell wall modification, general stress responses, fatty acid and amino acid catabolism, and cation transport were found to be upregulated, while glucose and gluconeogenesis genes were repressed. The same group recently demonstrated that the bactericidal activity of fusaricidin C coincided with an increased production of free hydroxyl radicals (51). Although a greater emphasis has been placed on membrane damage, it is also possible that fusaricidins inhibit intracellular targets.…”

Rapid Detection of Escherichia coli Antibiotic Susceptibility Using Live/Dead Spectrometry for Lytic Agents

“…Examination of the impact of dye interaction on green emissions is an additional measure of viability alongside red fluorescence intensity from PI only stained cells and the ADR. The literature pertaining to application of the BacLight Kit to assess bacterial viability has only used the green:red fluorescence ratio as a measure of the proportion of viable cells [ 17 , 39 , 45 , 46 , 47 , 48 ]. The work presented here uses the approach outlined in our previous publication [ 42 ] .…”