# Clonal spread of Mycobacterium monacense strains among patients with extrapulmonary mycobacteriosis

**Authors:** Christoffel Opperman, Aysha Ahmed, Marianna De Kock, Claudia Spies, Michael Biggel, Tristen Lourens, Sarishna Singh, Yonas Ghebrekristos, Robin Warren, Wynand Goosen, Giovanni Ghielmetti

PMC · DOI: 10.1007/s10096-025-05318-y · European Journal of Clinical Microbiology & Infectious Diseases · 2025-10-28

## TL;DR

This study shows that Mycobacterium monacense strains are spreading in specific areas in South Africa and suggests that drugs used for tuberculosis may also work against this rare bacteria.

## Contribution

The study identifies clonal spread of Mycobacterium monacense and evaluates the effectiveness of tuberculosis drugs against it using genomic and antimicrobial data.

## Key findings

- Mycobacterium monacense isolates show clonal spread within specific geographic regions.
- Isolates are susceptible to aminoglycosides, fluoroquinolones, and macrolides but show elevated resistance to β-lactam antibiotics.
- Drugs used for tuberculosis, like bedaquiline and linezolid, are effective against Mycobacterium monacense.

## Abstract

This study presents the phylogenetic and antimicrobial susceptibility characterization of Mycobacterium monacense, a rare nontuberculous mycobacterium (NTM), cultured from clinical extrapulmonary samples.

Eight Mycobacterium monacense isolates were identified between 2019 and 2023 in the Western Cape province of South Africa. Whole-genome sequencing (WGS) was applied to assess phylogenetic relatedness, identify virulence factors, and characterize the resistome of the isolates. Antimicrobial susceptibility testing (AST) was performed using the GenoType NTM-DR line probe assay (LPA), Sensititre minimum inhibitory concentrations (MIC) plates, and the proportional method based on critical concentrations. Spatial distribution of cases was mapped using ArcGIS software.

Spatiotemporal distribution patterns indicated the presence of circulating clones confined within specific geographical areas. Plasmids coding for ferredoxin and cytochrome P450 genes were identified in one cluster, which notably lacked the chromosomal mbtH gene involved in siderophore biosynthesis for iron acquisition. In contrast, isolates grouped in a second cluster harbored the mbtH chromosomal gene but lacked these plasmid-associated elements. LPA and broth microdilution showed that all Mycobacterium monacense isolates were susceptible to aminoglycosides, fluoroquinolones, and macrolides, but generally exhibited elevated MICs against β-lactam antibiotics. Phenotypic AST indicated that drugs commonly used to treat Mycobacterium tuberculosis complex (MTBC), namely bedaquiline, linezolid, and rifampicin, are effective against Mycobacterium monacense.

Mycobacterium monacense in extrapulmonary cultures accentuates the need for improved diagnostics and enhanced clinical awareness of infections with rare NTM. WGS highlights the potential significance provided by plasmid-encoded genes. Current treatment regimens for MTBC exhibit therapeutic efficacy against Mycobacterium monacense isolates.

The online version contains supplementary material available at 10.1007/s10096-025-05318-y.

## Linked entities

- **Genes:** mbtH (stimulator of DhbF tyrosine adenylation activity) [NCBI Gene 8303138]
- **Chemicals:** bedaquiline (PubChem CID 5388906), linezolid (PubChem CID 3929), rifampicin (PubChem CID 135398735)
- **Species:** Mycobacterium tuberculosis complex (taxon 77643)

## Full-text entities

- **Genes:** CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}
- **Diseases:** mycobacteriosis (MESH:D009165), infections (MESH:D007239)
- **Chemicals:** fluoroquinolones (MESH:D024841), beta-lactam (MESH:D047090), aminoglycosides (MESH:D000617), rifampicin (MESH:D012293), linezolid (MESH:D000069349), iron (MESH:D007501), macrolides (MESH:D018942), bedaquiline (MESH:C493870)
- **Species:** Mycobacterium tuberculosis complex (species group) [taxon 77643], Mycolicibacterium monacense (species) [taxon 85693], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12987876/full.md

## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12987876/full.md

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Source: https://tomesphere.com/paper/PMC12987876