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

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.

Pangenome mining of theStreptomycesgenus redefines their biosynthetic potential

“…Genome sizes spanned from 4.8 Mbp to 13.6 Mbp, with a median of 8.5 Mbp (Figure 1B). Interestingly, the strains with the smallest genome sizes mainly belong to actinomycetoma-related pathogenic species of S. sudanensis and S. somaliensis [22]. In contrast, the largest-sized genomes primarily belong to S. rapamycinicus or to novel species.…”

Chemistry and biology of specialized metabolites produced by Actinomadura

“…However, their role in pathogenesis is not yet well understood. 10 Bioinformatics analysis of the sequenced genomes of several of these isolates 245 indicates that their genomes each contain more than 25 biosynthetic gene clusters, most of which are so far predicted to produce unknown metabolites. Understanding the secondary metabolites produced by these organisms could provide insights into their potential role in the actinomycetoma disease process.…”

“…Based on in silico molecular docking studies it was suggested that CCpI could bind to various bacterial target molecules but the ndings were not supported experimentally. 205 Methyl-2-(2 ′hydroxyphenyl)-2-oxazoline-4-carboxylate (245), isolated from a fermentation of Actinomadura strain MJ502-77F8, had moderate activity against Gram-positive bacteria, including different strains of S. aureus and B. subtilis. 206 Carbazole alkaloids carbazomadurins A (246) and B (247), produced by A. madurae 2808-SV1, were identied during screening for the molecules protecting neuronal cells from glutamate toxicity.…”

Metagenomics-based exploration of key soil microorganisms contributing to continuously planted Casuarina equisetifolia growth inhibition and their interactions with soil nutrient transformation

“…Actinomadura is conducive to improving cycling capacity of soil C and N and increasing soil available nutrient content, however, continuous planting reduces Actinomadura abundance, which in turn hinders soil nutrient cycling and inhibits plant growth ( Zhang et al., 2020 ; Lu et al., 2023 ). Meanwhile, Actinomadura has a strong antimicrobial sensitivity and can effectively inhibit soil pathogens and promote plant growth ( Li et al., 2022 ; Watson et al., 2022 ). Mycobacterium has an important role in degrading soil hazardous substances, and a large number of studies have shown that increasing the abundance of Mycobacterium sp in soil can reduce the content of different types of soil hazardous substances, improve soil texture, and promote soil nutrients cycling for healthy plant growth ( Kim et al., 2013 ; Kandil et al., 2015 ; Li et al., 2021a ; Zhao X. et al., 2021 ).…”