| Title: |
GplR1, an unusual TetR-like transcription factor in Mycobacterium abscessus, controls the production of cell wall glycopeptidolipids, colony morphology, and virulence |
| Authors: |
Scarlet S. Shell; Michal Bar-Oz; Junpei Xiao; Manitosh Pandey; Juan Bellardinelli; Opeyemi I. Ibitoye; Mary Jackson; Stefan H. Oehlers; Daniel Barkan; Michal Meir |
| Source: |
mSystems, Vol 10, Iss 9 (2025) |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2025 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Mycobacterium; abscessus; transcriptional regulation; virulence regulation; glycopeptidolipid; GPL; Microbiology; QR1-502 |
| Description: |
Mycobacterium abscessus is a major human pathogen, mostly infecting people with pre-existing lung conditions, such as cystic fibrosis. The production of glycopeptidolipids (GPL) is a major determinant of virulence of this bacterium, with clinical isolates that lack GPL generally exhibiting more aggressive clinical behavior. The current paradigm is that GPL production is abolished in vivo via irreversible, spontaneous mutations taking place as part of in-host evolution. Little is known about the mechanisms or extent to which GPL production may be regulated. Here, we describe an unusual TetR-like transcription factor of M. abscessus, mab_1638, that appears to be a strong positive regulator of the entire GPL biosynthesis and export gene cluster through a combination of direct and indirect mechanisms. The inactivation of mab_1638 abolished GPL production, leading to stable rough colony morphology and increased virulence in infection models, characteristics of rough, non-GPL producers. Transcriptome analysis found that the mab_1638 mutant had 118 differentially expressed genes, including the GPL locus and a second, recently described GPL-like locus that produces a related glycosylated lipopeptide called GP8L. Chromatin immunoprecipitation and sequencing revealed a consensus inverted-repeat DNA sequence motif, characteristic of genes regulated by mab_1638. Together, these findings found that mab_1638 encodes a transcription factor required for GPL production and, therefore, has a profound effect on virulence traits. We propose naming this gene GPL regulator 1 (gplR1). This finding raises the important possibility that M. abscessus strains appearing smooth in laboratory growth conditions may nonetheless downregulate GPL-cluster genes in other conditions, including in-patient conditions, and thus acquire the phenotypic characteristics of rough strains.IMPORTANCEMycobacterium abscessus is an important human pathogen, causing disease that is difficult to treat. M. abscessus strains have been observed to have two ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doaj.org/toc/2379-5077; https://doaj.org/article/91b2959780694e95a3858fd2e9f9de98 |
| DOI: |
10.1128/msystems.00872-25 |
| Availability: |
https://doi.org/10.1128/msystems.00872-25; https://doaj.org/article/91b2959780694e95a3858fd2e9f9de98 |
| Accession Number: |
edsbas.54B0E9FD |
| Database: |
BASE |