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Systematic whole-genome sequencing reveals an unexpected diversity among actinomycetoma pathogens and provides insights into their antibacterial susceptibilities

Lookup NU author(s): Andrew Watson, Dr Bernhard Kepplinger, Dr Jon Chapman, Dr Nicholas Allenby, Dr Katarzyna Mickiewicz, Professor Michael Goodfellow, Professor Jeff Errington

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the β-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment.


Publication metadata

Author(s): Watson AK, Kepplinger B, Bakhiet SM, Mhmoud NA, Chapman J, Allenby NE, Mickiewicz K, Goodfellow M, Fahal AH, Errington J

Publication type: Article

Publication status: Published

Journal: PLoS Neglected Tropical Diseases

Year: 2022

Volume: 16

Issue: 7

Online publication date: 25/07/2022

Acceptance date: 29/06/2022

Date deposited: 01/09/2022

ISSN (electronic): 1935-2735

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pntd.0010128

DOI: 10.1371/journal.pntd.0010128

PubMed id: 35877680


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Funding

Funder referenceFunder name
209500
Wellcome Investigator Grant

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