Under the microscope, a tug-of-war concerning life and health has persisted for decades.
The fight against animal parasites is a silent war waged in the microscopic world. According to statistics, 1 the Chinese animal parasite control drug market reached tens of billions of RMB in 2024, with the global market being even larger and continuously growing.
Traditional antiparasitic drugs work by interfering with key physiological processes of parasites. For example, macrolide drugs like ivermectin target glutamate-gated chloride channels in the parasite's nervous system, causing paralysis and death 4 .
In veterinary medicine, parasitic infections not only cause growth retardation and reduced production in economic animals but also pose a major threat to the health of companion animals.
In the battlefield of antiparasitic drugs, parasites demonstrate remarkable evolutionary capabilities. They evade drug killing through various mechanisms, with P-glycoprotein playing a particularly crucial role 4 .
P-glycoprotein is a drug efflux pump that can expel drugs from the worm's body, reducing intracellular drug concentration, thus allowing parasites to survive.
A 2025 study published in Parasites & Vectors provided the first direct evidence that PGP-9 plays a central role in C. elegans tolerance to multiple drugs 4 .
Researchers found that PGP-9 not only has efflux function for ivermectin but is also effective against moxidectin, eprinomectin, and tunicamycin.
| Drug Name | Resistance Factor in Resistant Strains | Fold Increase in Sensitivity After pgp-9 Deletion |
|---|---|---|
| Ivermectin | Not specified | Not specified |
| Moxidectin | 2.2 | 2.6 |
| Eprinomectin | 6.3 | 7.8 |
| Tunicamycin | Showed tolerance | Restored to near wild-type levels |
To deeply investigate the multidrug transport function of PGP-9, researchers conducted a series of precise experiments. They used ivermectin-resistant C. elegans strain IVR10 as the research object and constructed pgp-9 gene knockout strains 4 .
Assessing the effect of drugs on larval development of different worm strains to precisely measure changes in drug sensitivity.
Using DiI12(3) dye to label amphid neurons and analyze amphid structure function.
Using RT-qPCR technology to detect pgp-9 and other related gene expression levels.
| Genotype | IC50 of IVM (nM) | Sensitivity Change Compared to IVR10 |
|---|---|---|
| IVR10 | Not specified | Baseline |
| IVR10(△pgp-9) | Not specified | Increased sensitivity |
| IVR10(△nhr-8) | Not specified | 2.9-fold increase |
| IVR10(△nhr-8) + pgp-9 silencing | 2.44±0.56 | Synergistic sensitivity increase |
Facing increasingly severe drug resistance problems, scientists are opening up unprecedented pathways to combat parasites. Biological control as an environmentally friendly alternative shows great potential 3 .
Using antagonistic relationships in nature to precisely intervene in the parasite life cycle through living organisms like fungi and bacteria.
For example, combined use of Beauveria bassiana with plant secondary metabolites (tannic acid) increased inhibition efficiency against Haemonchus contortus to 89% 3 .
At the 2025 ACS Fall Meeting's "First Time Disclosure" session, Novartis disclosed a new drug IID432 for Chagas disease 2 .
This drug selectively inhibits Trypanosoma cruzi topoisomerase II, blocking DNA replication, showing strong activity in vitro (EC50 only 8 nM).
Another innovative strategy shifts the target from the parasite to the host. A study on Cryptosporidium infection found that parasites rely on host cell glutathione to combat oxidative stress 9 .
Based on this discovery, researchers tested a drug called lapachone that blocks squalene production in host cells.
| Strategy Type | Mechanism of Action | Representative Drug/Organism | Advantage Characteristics |
|---|---|---|---|
| Biological Control | Using microbial pathogens to prey on or parasitize parasites | Beauveria bassiana | Environmentally friendly, high specificity |
| New Target Drugs | Inhibiting parasite topoisomerase II, blocking DNA replication | IID432 | Single administration can cure, no recurrence after discontinuation |
| Host-Directed Therapy | Targeting host metabolic pathways, cutting off parasite nutrition sources | Lapachone | Using drugs with existing safety data, accelerating clinical process |
Modern parasitology research relies on a series of powerful tools that enable scientists to analyze parasite biological characteristics at the molecular level and develop more effective interventions.
Playing an increasingly important role in molecular parasitology 8 .
In Toxoplasma research, scientists used CRISPR technology to construct BAG1 gene knockout strains, revealing complex compensatory mechanisms between heat shock protein family genes.
A key tool for detailed analysis of proteins in parasites and their extracellular vesicles.
Researchers conducted detailed proteomic analysis of extracellular vesicles produced by Toxoplasma when cultured in different host cell types, identifying 1833 proteins associated with the Toxoplasma genome, with 1392 reliably quantified 8 .
For precise editing of parasite genes, revealing gene function and resistance mechanisms 8
For proteomic analysis, identifying and quantifying protein composition in parasites and their vesicles 8
Assessing the impact of drugs on parasite development, quantitatively measuring drug sensitivity 4
Determining the quantity and particle size distribution of extracellular vesicles, revealing intercellular communication mechanisms 8
Simulating in vivo environments, evaluating drug efficacy under near-real conditions 6
With continuous advancement in scientific technology, the development of animal antiparasitic drugs is entering a completely new stage. By 2032, the biocontrol agent market is expected to grow at a CAGR of 15.5%, reaching $21.5 billion 7 .
Future antiparasitic strategies will become more integrated and personalized. Integrated Pest Management strategies increasingly incorporate biocontrol agents as fundamental components, combined with precision medication, to delay resistance development 3 .
Artificial intelligence and machine learning are transforming the biocontrol agent market by introducing unparalleled precision, efficiency, and innovation.
These technologies can analyze massive data from sensors, drones, and satellite imagery to identify pest hotspots, predict outbreak epidemics, and recommend optimal application timing and dosage for biocontrol agents 7 .
Researchers are finding inspiration from parasite-host interactions. Toxoplasma manipulates host cells by releasing extracellular vesicles that "tailor" their protein composition according to the different host types they infect 8 .
Meanwhile, Cryptosporidium's loss of the ability to produce glutathione during evolution has instead become its potential fatal weakness 9 .
Understanding these sophisticated mechanisms not only opens new pathways for drug development but also gives us a deeper understanding of the complex interactions in the living world.
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