Targeting a microbiota Wolbachian aminoacyl-tRNA synthetase to block its pathogenic host.

Hoffmann, Guillaume, Lukarska, Maria, Clare, Rachel ORCID: https://orcid.org/0000-0002-3945-0530, Masters, Ellen, Johnston, Kelly, Ford, Louise, Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192, Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275, Jensen, Malene Ringkjøbing and Palencia, Andrés (2024) 'Targeting a microbiota Wolbachian aminoacyl-tRNA synthetase to block its pathogenic host.'. Science Advances, Vol 10, Issue 28, eado1453.

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Abstract

The interplay between humans and their microbiome is crucial for various physiological processes, including nutrient absorption, immune defense, and maintaining homeostasis. Microbiome alterations can directly contribute to diseases or heighten their likelihood. This relationship extends beyond humans; microbiota play vital roles in other organisms, including eukaryotic pathogens causing severe diseases. Notably, Wolbachia, a bacterial microbiota, is essential for parasitic worms responsible for lymphatic filariasis and onchocerciasis, devastating human illnesses. Given the lack of rapid cures for these infections and the limitations of current treatments, new drugs are imperative. Here, we disrupt Wolbachia's symbiosis with pathogens using boron-based compounds targeting an unprecedented Wolbachia enzyme, leucyl-tRNA synthetase (LeuRS), effectively inhibiting its growth. Through a compound demonstrating anti-Wolbachia efficacy in infected cells, we use biophysical experiments and x-ray crystallography to elucidate the mechanism behind Wolbachia LeuRS inhibition. We reveal that these compounds form adenosine-based adducts inhibiting protein synthesis. Overall, our study underscores the potential of disrupting key microbiota to control infections.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole. QX Parasitology > QX 20 Research (General) QX Parasitology > Helminths. Annelida > QX 203 Nematoda QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1126/sciadv.ado1453
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	24 Jul 2024 13:36
Last Modified:	24 Jul 2024 13:36
URI:	https://archive.lstmed.ac.uk/id/eprint/24942

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