Enhancement of the antibiofilm activity of amphotericin B by polyamine biosynthesis inhibitors.
The aim of this study was to investigate the effect of polyamine biosynthesis inhibitors on the activity of amphotericin B (AmB) against Candida albicans biofilms and to clarify the underlying mechanisms. The antibiofilm activity of AmB was significantly enhanced when used in combination with the polyamine biosynthesis inhibitors 1,4-diamino-2-butanone (DAB) and α-difluoromethylornithine (DFMO). Further study showed that DAB and DFMO also enhanced the antibiofilm activity of several other antifungal agents. Moreover, the combination of AmB and polyamine biosynthesis inhibitors resulted in an increase in intracellular levels of reactive oxygen species. In addition, caspase activity and transcription of the caspase-encoding gene CaMCA1 were greatly increased upon combined treatment with polyamine biosynthesis inhibitors and AmB. Consistently, the biofilm formed by a Δcamca1 mutant exhibited greater viability and lower caspase activity than that of the wild-type strain upon combined treatment. These data provide useful information for the development of new strategies to enhance the antibiofilm activities of antifungal agents.
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
ZeBin
Z
Liao
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
XuanZi
X
ZhangGuan
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
ZhenYu
Z
Zhu
Pharmacy Department, General Hospital of Jiangsu Armed Police, No. 8 Jiangdu South Road, Yangzhou 225000, China.
XiangWen
X
Yao
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
Yu
Y
Yang
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: 13761571578@163.com.
YuanYing
Y
Jiang
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: caoyingying608@163.com.
YingYing
Y
Cao
D000666:Amphotericin B / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D000518:Eflornithine / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011073:Polyamines / Q000494:pharmacology*
D000890:Anti-Infective Agents; D011073:Polyamines; D000666:Amphotericin B; D000518:Eflornithine
Amphotericin B; Biofilm; CaMCA1; Candida albicans; Caspase; Polyamine biosynthesis inhibitor