Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages
Abstract In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.tb‘s complex and protective cell envelope has been widely studied, little is known about how levels of peripheral lipids...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-81457-0 |
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| author | Alyssa Schami M. Nurul Islam Matthew Wall Amberlee Hicks Reagan Meredith Barry Kreiswirth Barun Mathema John T. Belisle Jordi B. Torrelles |
| author_facet | Alyssa Schami M. Nurul Islam Matthew Wall Amberlee Hicks Reagan Meredith Barry Kreiswirth Barun Mathema John T. Belisle Jordi B. Torrelles |
| author_sort | Alyssa Schami |
| collection | DOAJ |
| description | Abstract In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.tb‘s complex and protective cell envelope has been widely studied, little is known about how levels of peripheral lipids change in relation to drug resistance. In this study, we examined levels of cell envelope lipids [phthiocerol dimycocerosates (PDIMs)], glycolipids [phosphatidyl-myo-inositol mannosides (PIMs)], and PIMs associated lipoglycans [lipomannan (LM); mannose-capped lipoarabinomannan (ManLAM)] of 22 M.tb strains that ranged in drug resistance profile. We show that the PDIMs:PIMs ratio increases as drug resistance increases, and provide evidence of PDIM isomers only present in the DR-M.tb strains studied. Overall, the LM and ManLAM levels did not differ between drug resistance categories, but ManLAM surface exposure increased with drug resistance. Infection of human macrophages revealed that DR-M.tb strains have decreased association compared to drug susceptible (DS) strains, and that the pre-XDR M.tb strain with the largest PDIMs:PIMs ratio had decreased uptake, but increased intracellular growth at early during infection compared to the DS-M.tb strain H37Rv. These findings suggest that PDIMs may play an important role in drug resistance and that an increase in hydrophobic cell envelope lipids may influence M.tb-host interactions. |
| format | Article |
| id | doaj-art-d87e04e1822447feb537f16d0b585693 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d87e04e1822447feb537f16d0b5856932025-08-20T03:01:34ZengNature PortfolioScientific Reports2045-23222024-12-0114112210.1038/s41598-024-81457-0Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophagesAlyssa Schami0M. Nurul Islam1Matthew Wall2Amberlee Hicks3Reagan Meredith4Barry Kreiswirth5Barun Mathema6John T. Belisle7Jordi B. Torrelles8Population Health and Host Pathogen Interactions Programs, Texas Biomedical Research InstituteMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State UniversityPopulation Health and Host Pathogen Interactions Programs, Texas Biomedical Research InstitutePopulation Health and Host Pathogen Interactions Programs, Texas Biomedical Research InstitutePopulation Health and Host Pathogen Interactions Programs, Texas Biomedical Research InstituteCenter for Discovery and Innovation, Hackensack Meridian HealthDepartment of Epidemiology, Columbia University Mailman School of Public HealthMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State UniversityPopulation Health and Host Pathogen Interactions Programs, Texas Biomedical Research InstituteAbstract In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.tb‘s complex and protective cell envelope has been widely studied, little is known about how levels of peripheral lipids change in relation to drug resistance. In this study, we examined levels of cell envelope lipids [phthiocerol dimycocerosates (PDIMs)], glycolipids [phosphatidyl-myo-inositol mannosides (PIMs)], and PIMs associated lipoglycans [lipomannan (LM); mannose-capped lipoarabinomannan (ManLAM)] of 22 M.tb strains that ranged in drug resistance profile. We show that the PDIMs:PIMs ratio increases as drug resistance increases, and provide evidence of PDIM isomers only present in the DR-M.tb strains studied. Overall, the LM and ManLAM levels did not differ between drug resistance categories, but ManLAM surface exposure increased with drug resistance. Infection of human macrophages revealed that DR-M.tb strains have decreased association compared to drug susceptible (DS) strains, and that the pre-XDR M.tb strain with the largest PDIMs:PIMs ratio had decreased uptake, but increased intracellular growth at early during infection compared to the DS-M.tb strain H37Rv. These findings suggest that PDIMs may play an important role in drug resistance and that an increase in hydrophobic cell envelope lipids may influence M.tb-host interactions.https://doi.org/10.1038/s41598-024-81457-0Mycobacterium tuberculosisDrug resistanceCell envelope compositionPhthiocerol dimycocerosatesPhosphatidyl-myo-inositol mannosidesTuberculosis |
| spellingShingle | Alyssa Schami M. Nurul Islam Matthew Wall Amberlee Hicks Reagan Meredith Barry Kreiswirth Barun Mathema John T. Belisle Jordi B. Torrelles Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages Scientific Reports Mycobacterium tuberculosis Drug resistance Cell envelope composition Phthiocerol dimycocerosates Phosphatidyl-myo-inositol mannosides Tuberculosis |
| title | Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages |
| title_full | Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages |
| title_fullStr | Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages |
| title_full_unstemmed | Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages |
| title_short | Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages |
| title_sort | drug resistant mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages |
| topic | Mycobacterium tuberculosis Drug resistance Cell envelope composition Phthiocerol dimycocerosates Phosphatidyl-myo-inositol mannosides Tuberculosis |
| url | https://doi.org/10.1038/s41598-024-81457-0 |
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