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Resistance towards metronidazole in Blastocystis sp.: A pathogenic consequence
Arutchelvan Rajamanikam1, Ho Shiaw Hooi2, Madhav Kudva3
1Depatment of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Abstract:
Blastocsytis sp. is a protozoan parasite that has been linked to common gastrointestinal illnesses. Metronidazole, the first line therapy, was reported to show frequent inefficacy. Previously, Blastocystis sp. isolated from different population showed varying metronidazole resistance. However, the effect of metronidazole treatment on pathogenic potentials of Blastocystis sp. isolated from different populations, which is known to have different gut environment, is unclear. This study investigates the in vitro effect of metronidazole on the pathogenic potentials of Blastocystis sp. isolated from urban and orang asli individuals. Blastocystis sp. ST 3 isolated from symptomatic and asymptomatic individuals were treated with a range of metronidazole concentration. The parasites' growth characteristics, apoptotic rate, specific protease activity and the ability to proliferate cancer cells were analyzed upon treatment with 0.001 mg/l metronidazole. The study demonstrates that Blastocystis sp. isolates showed increase in the parasite numbers especially the amoebic forms (only in urban isolates) after treating with metronidazole at the concentration of 0.001 mg/ml. High number of cells in post-treated isolates coincided with increase of apoptosis. There was a significant increase in cysteine protease of Blastocystis sp. isolates upon treatment despite the initial predominance of serine protease in asymptomatic isolates. Metronidazole resistant Blastocystis sp. also showed significant increase in cancer cell proliferation. Resistance to metronidazole did not show significant different influence on the pathogenicity between Blastocystis sp. isolated from urban and orang asli individual. However, an increase in parasite numbers, higher amoebic forms, cysteine protease and ability to proliferate cancer cells implicates a pathogenic role. The study provides evidence for the first time, the effect of metronidazole towards enhancing pathogenic potentials in Blastocystis sp. when isolated from different gut environment. This necessitates the need for reassessment of metronidazole treatment modalities.
Insights
Metronidazole treatment may unexpectedly increase the pathogenicity of Blastocystis sp. parasites, including enhanced growth and cancer cell proliferation. This finding necessitates a reevaluation of current treatment strategies for gastrointestinal infections caused by this protozoan.
Area of Science:
- Microbiology
- Parasitology
- Gastroenterology
Background:
- Blastocystis sp. is a common protozoan parasite causing gastrointestinal issues.
- Metronidazole, a primary treatment, often shows inefficacy and variable resistance.
- The impact of metronidazole on Blastocystis sp. pathogenicity across different host gut environments remains unclear.
Purpose of the Study:
- To investigate the in vitro effect of metronidazole on the pathogenic potentials of Blastocystis sp. from urban and indigenous populations.
- To analyze changes in parasite growth, apoptosis, protease activity, and cancer cell proliferation after metronidazole treatment.
Main Methods:
- Blastocystis sp. ST 3 isolates from symptomatic and asymptomatic individuals were exposed to varying metronidazole concentrations.
- Parasite growth, apoptotic rates, cysteine protease activity, and cancer cell proliferation were assessed post-treatment.
- Comparative analysis was performed between urban and indigenous isolates.
Main Results:
- Metronidazole treatment (0.001 mg/ml) increased Blastocystis sp. numbers, particularly amoebic forms in urban isolates.
- Post-treatment isolates exhibited higher apoptosis rates and significantly increased cysteine protease activity.
- Metronidazole-resistant Blastocystis sp. demonstrated enhanced cancer cell proliferation.
- Pathogenicity differences between urban and indigenous isolates were not significant post-treatment.
Conclusions:
- Metronidazole treatment can paradoxically enhance the pathogenic potential of Blastocystis sp., including increased proliferation and cancer cell invasiveness.
- The study highlights the need to reassess metronidazole treatment protocols for Blastocystis sp. infections.
- Findings suggest metronidazole may alter parasite virulence factors, necessitating further investigation into treatment efficacy and host-parasite interactions.
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