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Bioactive phytocompounds against specific target proteins of Borrelia recurrentis responsible for louse-borne relapsing fever: Genomics and structural bioinformatics evidence

This plain language summary is part of the Neglected Bacterial Diseases Special Issue published in Medical and Veterinary Entomology in May 2023. Read the full article, free for a limited time here.

Louse-borne relapsing fever or LBRF, caused by the human-body louse harboring spirochete Borrelia recurrentis was endemic to the Horn of Africa. It is an ancient epidemic disease linked to war, famine, poverty, forced migration, and crowding under poor hygienic conditions. The disease was first documented by Craigie and Henderson in 1843. It had a massive impact, especially following political crisis, socioeconomic disaster, and war. LBRF subsequently gained focus at various points owing to sporadic outbreaks in various parts of the world owing to migrations.

To enhance the therapeutic regimen against LBRF Borrelia, understanding the conservation of drug-targets is crucial. So, we examined the conservation of common drug-targets in phylogenetically distinct tick- and louse-borne Borrelia. We evaluated the comparative efficacy of 12 anti-Lyme-disease phytocompounds like hydroxy-tyrosol, baicalein, cis-2-decanoic acid, morin, oenin, rosemarinic acid, kaempferol, piceatannol, rottlerin, luteolin, fisetin and monolaurin against LBRF Borrelia targets. Whole genome assemblies comprising the Lyme disease spirochete B. burgdorferi, tick-borne relapsing fever species B. hermsii and B. parkeri, hard tick-borne relapsing fever species B. miyamotoi, and LBRF species B. recurrentis were retrieved. Based on the traditional targets of anti-Borrelia antibiotics like tetracycline, benzylpenicillin, and chloramphenicol, the drug-target proteins were prioritized. We utilized an extended-modelling technique previously developed by our team to model the unavailable protein structures. The 30S ribosomal subunit proteins, penicillin-binding protein-2, and 50S ribosomal subunit protein were identified as typical Borrelia protein targets involved in protein translation and membrane integrity. When compared to the Lyme-disease spirochete B. burgdorferi, multiple sequence alignments showed that the target proteins from LBRF and tick-borne RF Borrelia spp. shared >70% similarity. Interestingly, all 12 phytocompounds showed multi-target and multi-species specificity for Borrelia. Based on target-affinity and pharmacological safety, luteolin displayed the best profile among the phytochemicals. Luteolin, a flavonoid, obtained from balsamic sage and dyer’s weed, has been used in Chinese traditional medicine for multiple advantages. Since extended antibiotic treatment for RF Borrelia is not advised due to side effects, pharmacologically safe luteolin offers promise. During RF therapy, a Jarisch-Herxheimer (JH) reaction brought on by antibiotic-driven rapid death of spirochetes to release toxins is frequently observed. The anti-inflammatory, antipyretic, and analgesic characteristics of luteolin can lessen the severity of JH responses. Furthermore, multi-target specific drug-candidates like luteolin may prove fruitful against resistant organisms with specific drug-target mutations.

Considering the healthcare turmoil in recent years, is it always advantageous to enrich therapeutic regimen to safeguard ourselves from unforeseen threats posed by the evolving microscopic pathogenic entities.

We have to remember the quote from Stephen Gould:

Bacteria represent the world’s greatest success story. They are today and have always been the modal organisms on earth; they cannot be nuked to oblivion and will outlive us all.”

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