Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis
Abstract Under stress, bacteria display selective growth propensities on solid and liquid media. For Mycobacterium tuberculosis (Mtb), differentially culturable bacteria have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce selective culturability i...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-85092-7 |
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| author | Valerie F. A. March Nino Maghradze Kakha Mchedlishvili Teona Avaliani Rusudan Aspindzelashvili Zaza Avaliani Maia Kipiani Nestani Tukvadze Levan Jugheli Selim Bouaouina Anna Doetsch Galo A. Goig Sebastien Gagneux Sonia Borrell |
| author_facet | Valerie F. A. March Nino Maghradze Kakha Mchedlishvili Teona Avaliani Rusudan Aspindzelashvili Zaza Avaliani Maia Kipiani Nestani Tukvadze Levan Jugheli Selim Bouaouina Anna Doetsch Galo A. Goig Sebastien Gagneux Sonia Borrell |
| author_sort | Valerie F. A. March |
| collection | DOAJ |
| description | Abstract Under stress, bacteria display selective growth propensities on solid and liquid media. For Mycobacterium tuberculosis (Mtb), differentially culturable bacteria have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce selective culturability in Mtb. We investigated the effect of exposure to TB drugs on Mtb culturability using clinical samples from an ongoing TB patient cohort and by conducting several in vitro experiments with a diverse set of Mtb strains. In patients, serial sputa were more likely to generate Mtb-positive cultures in liquid as opposed to solid medium, with this liquid culture bias extending up to 5 months post diagnosis. Experimentally, there was a disparity between bacterial time to positivity (TTP) and colony forming units (CFUs) when Mtb was exposed to isoniazid (INH) and rifampicin (RIF) alone or in combination. Cultures recovered from RIF treatment yielded more CFUs on agar plates, but INH-treated cultures had a faster TTP in liquid. Follow up experiments using a fluorescently labelled laboratory strain of Mtb revealed that CFUs of INH-treated bacteria were too low, thus over-estimating the killing effect of the treatment. Here we provide evidence that drug exposure affects culturability on solid medium in diverse Mtb strains, which has implications for treatment monitoring and drug-pathogen interaction studies. |
| format | Article |
| id | doaj-art-b9a731c24a0f4e7085eddaca931f0157 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b9a731c24a0f4e7085eddaca931f01572025-02-02T12:17:14ZengNature PortfolioScientific Reports2045-23222025-01-011511810.1038/s41598-024-85092-7Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosisValerie F. A. March0Nino Maghradze1Kakha Mchedlishvili2Teona Avaliani3Rusudan Aspindzelashvili4Zaza Avaliani5Maia Kipiani6Nestani Tukvadze7Levan Jugheli8Selim Bouaouina9Anna Doetsch10Galo A. Goig11Sebastien Gagneux12Sonia Borrell13Swiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteNational Centre for Tuberculosis and Lung Diseases (NCTLD)National Centre for Tuberculosis and Lung Diseases (NCTLD)National Centre for Tuberculosis and Lung Diseases (NCTLD)National Centre for Tuberculosis and Lung Diseases (NCTLD)Swiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteAbstract Under stress, bacteria display selective growth propensities on solid and liquid media. For Mycobacterium tuberculosis (Mtb), differentially culturable bacteria have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce selective culturability in Mtb. We investigated the effect of exposure to TB drugs on Mtb culturability using clinical samples from an ongoing TB patient cohort and by conducting several in vitro experiments with a diverse set of Mtb strains. In patients, serial sputa were more likely to generate Mtb-positive cultures in liquid as opposed to solid medium, with this liquid culture bias extending up to 5 months post diagnosis. Experimentally, there was a disparity between bacterial time to positivity (TTP) and colony forming units (CFUs) when Mtb was exposed to isoniazid (INH) and rifampicin (RIF) alone or in combination. Cultures recovered from RIF treatment yielded more CFUs on agar plates, but INH-treated cultures had a faster TTP in liquid. Follow up experiments using a fluorescently labelled laboratory strain of Mtb revealed that CFUs of INH-treated bacteria were too low, thus over-estimating the killing effect of the treatment. Here we provide evidence that drug exposure affects culturability on solid medium in diverse Mtb strains, which has implications for treatment monitoring and drug-pathogen interaction studies.https://doi.org/10.1038/s41598-024-85092-7Mycobacterium tuberculosisCulturabilityViable but non culturable (VBNC)AntibioticsIsoniazidRifampicin |
| spellingShingle | Valerie F. A. March Nino Maghradze Kakha Mchedlishvili Teona Avaliani Rusudan Aspindzelashvili Zaza Avaliani Maia Kipiani Nestani Tukvadze Levan Jugheli Selim Bouaouina Anna Doetsch Galo A. Goig Sebastien Gagneux Sonia Borrell Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis Scientific Reports Mycobacterium tuberculosis Culturability Viable but non culturable (VBNC) Antibiotics Isoniazid Rifampicin |
| title | Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis |
| title_full | Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis |
| title_fullStr | Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis |
| title_full_unstemmed | Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis |
| title_short | Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis |
| title_sort | drug induced differential culturability in diverse strains of mycobacterium tuberculosis |
| topic | Mycobacterium tuberculosis Culturability Viable but non culturable (VBNC) Antibiotics Isoniazid Rifampicin |
| url | https://doi.org/10.1038/s41598-024-85092-7 |
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