Biology subjects

Cambau, E.

Publications and source records attributed to Cambau, E..

3 recordsLinked to original sources

bioRxiv2026

Emergence of plasmid-borne erm(55)-associated macrolide resistance in Mycobacterium chelonae and other rapidly-growing non-tuberculous mycobacteria in Europe

Macrolides are key agents for treating infections caused by non-tuberculous mycobacteria (NTM). Nevertheless, chromosomal erm genes conferring inducible macrolide resistance are described in some NTM species, such as Mycobacterium abscessus and M. fortuitum, whereas M. chelonae had long been considered as lacking a functional erm. Recent descriptions from the USA and Japan of a new plasmid-borne erm(55) (erm(55)P) in M. chelonae and other rapidly growing mycobacteria (RGM) have challenged this assumption. We investigated erm(55)P occurrence in clinical RGM referred to the French National Reference Centre for Mycobacteria between 2012 and 2026 by genome screening and erm(55)P specific real-time PCR. Positive isolates underwent long-read whole genome sequencing (GridIon, Oxford Nanopore Technologies). Clarithromycin (CLR) minimum inhibitory concentration (MIC) was determined by broth microdilution (RAPMYCO and FRATMYC, Thermo Fisher) and read up to 14 days. Five clinical isolates showing inducible CLR resistance (MIC range <0.25-64 mg/L on day 3-4 and 128- >128 mg/L on day 14) were positive for erm(55)P: one M. chelonae, three M. neoaurum, and one M. parafortuitum. erm(55)P-positive M. chelonae genomes from this and previous descriptions did not cluster together in the phylogenetic analysis of 263 genomes. The assembled plasmids showed high similarity to previously reported erm(55)-carrying plasmids, especially within the erm(55)P region. The upstream sequence of erm(55)P showed a secondary structure compatible with a possible translation attenuation mechanism. These findings document the first report of a plasmid-borne erm(55) in Europe in M. chelonae and other RGM and raise concern about the emergence of plasmid macrolide resistance in NTM.

microbiology↗

bioRxiv2026

Minimal effective dose of telacebec administered orally in a murine model of leprosy

Leprosy treatment requires prolonged therapy with challenging patient follow-up. New regimens are needed to simplify current treatments. A recent clinical trial evaluating bedaquiline has shown promising results; however, to prevent the emergence of drug resistance, additional therapeutic options are required. Telacebec (TCB), an imidazopyridine amide targeting the Mycobacterium leprae electron transport chain, represents a promising candidate. In this study, we determined the minimal effective dose (MED) of TCB against M. leprae in vivo by using the proportional bactericidal method in the mouse footpad model. Results were analyzed by using microscopy, RLEP qPCR and molecular viability. The MED obtained was 20 mg/kg. TCB doses [≥]20 mg/kg achieved complete bacterial clearance, similar to bedaquiline 25mg/kg. Molecular enumeration confirmed these findings whereas molecular viability assessment had limited applicability due to insufficient bacterial burden. These findings provide a strong foundation for clinical trial design and the development of combination therapies.

microbiology↗

bioRxiv2022

An updated evolutionary history and taxonomy of Mycobacterium tuberculosis lineage 5, also called M. africanum

Contrarily to other lineages such as L2 and L4, there are still scarce whole-genome-sequence data on L5-L6 MTBC clinical isolates in public genomes repositories. Recent results suggest a high complexity of L5 history in Africa. It is of importance for an adequate assessment of TB infection in Africa, that is still related to the presence of L5-L6 MTBC strains. This study reports a significant improvement of our knowledge of L5 diversity, phylogeographical history, and global population structure of Mycobacterium africanum L5. To achieve this aim, we sequenced new clinical isolates from Northern Nigeria and from proprietary collections, and used a new powerful bioinformatical pipeline, TB-Annotator that explores not only the shared SNPs but also shared missing genes, identical IS6110 insertion sites and shared regions of deletion. This study using both newly sequenced genomes and available public genomes allows to describe new L5 sublineages. We report that the MTBC L5 tree is made-up of at least 12 sublineages from which 6 are new descriptions. We confront our new classification to the most recent published one and suggest new naming for the discovered sublineages. Finally, we discuss the phylogeographical specificity of sublineages 5.1 and sublineage 5.2 and suggest a new hypothesis of L5-L6 emergence in Africa. Impact statementRecent studies on Mycobacterium africanum (L5-L6-L9 of MTBC) genomic diversity and its evolution in Africa discovered three new lineages of the Mycobacterium tuberculosis complex (MTBC) in the last ten years (L7, L8, L9). These discoveries are symptomatic of the delay in characterizing the diversity of the MTBC on the African continent. Another understudied part of MTBC diversity is the intra-lineage diversity of L5 and L6. This study unravels an hidden diversity of L5 in Africa and provides a more exhaustive description of specific genetic features of each sublineage by using a proprietary "TB-Annotator" pipeline. Furthermore, we identify different phylogeographical localization trends between L5.1 and L5.2, suggesting different histories. Our results suggest that a better understanding of the spatiotemporal dynamics of MTBC in Africa absolutely requires a large sampling effort and powerful tools to dig into the retrieved diversity. Data summary[A section describing all supporting external data, software or code, including the DOI(s) and/or accession numbers(s), and the associated URL. If no data was generated or reused in the research, please state this.] The search was done in the TB-Annotator 15901 genomes version which is available at: http://(to be added). The new sequenced genomes are available via NCBI Bioproject accession number: (to be added). The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

genomics↗