A lactoferricin-like peptide from centipede venom killed Candida albicans by triggering excessive nitric oxide, overwhelming glutathione defenses and disrupting mitochondria.
NO-mediated killingcentipede peptide triggers fatal nitric oxide accumulation in Candida, overwhelming its glutathione defense and causing mitochondrial collapse
What the researchers found
LBLP triggered endogenous nitric oxide (NO) production in Candida albicans through the NO synthase pathway. This nitric oxide overwhelmed the cell's glutathione defense system, leading to nitrosative stress.
The excess NO inhibited mitochondrial respiration and altered NAD+/NADH ratios. This disrupted the mitochondrial membrane potential, caused calcium homeostasis failure, and led to mitochondrial superoxide accumulation.
The cascade ultimately triggered apoptosis (programmed cell death) in the fungal cells. When researchers blocked NO production, all of these effects were reduced, confirming that NO is the central mechanism of LBLP's antifungal action.
Why it matters
Fungal infections are increasingly difficult to treat due to drug resistance. Antimicrobial peptides from natural sources like venoms offer a different mechanism of action that fungi may not easily develop resistance to.
Understanding exactly how LBLP kills fungi (through the NO pathway) could help researchers design better antifungal peptides or combination therapies.
The numbers in context
23-amino-acid peptide; NO-dependent killing; decreased glutathione; disrupted mitochondrial respiration and membrane potential; triggered apoptosis
How the study worked
This was a laboratory study using Candida albicans cultures. Researchers measured intracellular NO levels, glutathione, mitochondrial respiration, NAD+/NADH ratios, mitochondrial membrane potential, calcium levels, superoxide production, and apoptosis markers. They used NO synthase inhibitors to confirm the NO-dependent mechanism.
Who was studied
Candida albicans cultures
What this study cannot tell us
This was entirely an in vitro study. Whether LBLP can reach Candida infections in a living body, and whether it is safe for human cells at effective concentrations, is unknown.
The peptide comes from centipede venom, which may require significant modification for therapeutic use.
How to read the evidence
Preliminary evidence from in vitro Candida studies. Novel mechanism clearly demonstrated but safety and in vivo efficacy untested.
When this study was published
Published in 2020. Antimicrobial peptides from venom sources continue to be explored for drug development.
The bigger picture
Fungal infections are increasingly drug-resistant. This peptide uses a completely different mechanism than standard antifungals — turning the fungus's own nitric oxide against it. Resistance to this mechanism would be difficult to develop because it exploits fundamental metabolic pathways.
Questions still open
- Is LBLP safe for human cells at effective anti-Candida concentrations?
- Could this mechanism be exploited by designing synthetic NO-inducing peptides?
- Does LBLP work against drug-resistant Candida strains?
Common questions
How does this peptide kill fungi differently from standard drugs?
Could centipede venom peptides become medicines?
Read the original research
Lactoferricin B like peptide triggers mitochondrial disruption-mediated apoptosis by inhibiting respiration under nitric oxide accumulation in Candida albicans.
IUBMB life, 72(7), 1515-1527
Citation
Kim, Suhyun; Hwang, Jae Sam; Lee, Dong Gun. (2020). Lactoferricin B like peptide triggers mitochondrial disruption-mediated apoptosis by inhibiting respiration under nitric oxide accumulation in Candida albicans.. IUBMB life, 72(7), 1515-1527. https://doi.org/10.1002/iub.2284