The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative genomics to test the hypothesis that PFOR in eukaryotes was acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other putatively acquired genes, proteome-wide and gene enrichment analyses were used. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance the adaptation of protozoa in hostile environments. Comparative genomics of and the putative gene donor, , identified eleven candidate genes for HGT involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide more validated evidence to support the horizontal transfer of from bacteria.
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http://dx.doi.org/10.3390/biology13030178 | DOI Listing |
Biology (Basel)
March 2024
Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland.
The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative genomics to test the hypothesis that PFOR in eukaryotes was acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other putatively acquired genes, proteome-wide and gene enrichment analyses were used.
View Article and Find Full Text PDFPharmaceuticals (Basel)
February 2022
Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
The presence of "hypoxic" tissue (with O levels of <0.1 mmHg) in solid tumours, resulting in quiescent tumour cells distant from blood vessels, but capable of being reactivated by reoxygenation following conventional therapy (radiation or drugs), have long been known as a limitation to successful cancer chemotherapy. This has resulted in a sustained effort to develop nitroaromatic "hypoxia-activated prodrugs" designed to undergo enzyme-based nitro group reduction selectively in these hypoxic regions, to generate active drugs.
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