Preliminary Study On The Mechanism Of Mitochondrial Membrane Potential By Antimicrobial Peptide CGA-N12

The incidence of fungal infections,especially deep fungal infections increased year by year.Repeated or continuous exposure to common antibiotics,will result into pathogens drug resistance.Antimicrobial peptides have attracted considerable attention for their broad-spectrum antimicrobial activity and less possibility to cause bacterial resistance,and hopeful to be a potential antibiotics alternatives.CGA-N12 is one of the derivatives of antimicrobial peptide CGA-N46.The results of previous studies showed that CGA-N12 share similar anti-Candida mechanism with CGA-N46,reducing mitochondrial membrane potential.Compared with CGA-N46,CGA-N12 has higher anti-Candida activity,and the most sensitive fungus Candida albican was replaced with Candida tropicalis,a more meaningful clinical pathgen.Further study on the CGA-N12 molecular mechanisms of decreasing mitochondrial membrane potential is of great significance for the development of CGA-N12 to be a novel antimicrobial agent.mitochondrial permeability transition pore(mPTP)regulates mitochondrial membrane permeability.When mPTP is in the open state,the mitochondria membrane permeability increases,the membrane potential decreases,Ca2+ leakage,cytochrome c release.In this paper,mitochondria were extracted from Candida tropicalis by different eccentric speed.The mitochondria treated with the mPTP opening inhibitor CsA and mPTP opening activator Nd(III)were setas controls,effects of CGA-N12 on mitochondria membranepermeability were studied.The results showed that CGA-N12 has similar effect with Nd(III)on the mitochondrial.CGA-N12 could resulted in mitochondrial membrane potential decreasing,Ca2+ leakage and cytochrome c releaseing..In order to further study the molecular mechanism of CGA-N12 on mPTP,the effects of CGA-N12 on the mPTP post-treated by mPTP opening inhibitors CsA and DTT.CGA-N12 could eliminate the effect of CsA and DTT on m PTP,which indicated that CGA-N12 affected on the targets of CsA and DTT in mPTP.In summary,CGA-N12 reduce mitochondrial membrane potential through increasing the permeability of mitochondria,and its mechanism of increasing mitochondrial permeability needs further study.