ArticlePLoS pathogens2018
RD5-mediated lack of PE_PGRS and PPE-MPTR export in BCG vaccine strains results in strong reduction of antigenic repertoire but little impact on protection.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 46 citations in OpenAlex.
- Host-strain compatibility shapes host transcriptional responses in macrophageMicrobial genomics · 2026Article
- Pervasive genome structure heterogeneity iniScience · 2026Article
- Immunogenicity and protective efficacy of recombinant BCG expressing a multi-epitope vaccine against mycobacterium tuberculosis.Frontiers in cellular and infection microbiology · 2026Article
- ESX-5 Deletions inbioRxiv : the preprint server for biology · 2025Article
- Generation of novel polyclonal antibodies against Mycobacterium tuberculosis lipoarabinomannan, EspB, and Mtb8.Applied microbiology and biotechnology · 2025Article
- Loss of the ESX-5 secretion locus inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- PPE50 variants as novel phylogeographic signatures of host-pathogen co-evolution in tuberculosis.Communications biology · 2025Article
- Loss of theScience advances · 2025Article
- Evolution of the PE_PGRS Proteins of Mycobacteria: Are All Equal or Are Some More Equal than Others?Biology · 2025Review
- Article
- The PE/PPE family proteins ofFrontiers in immunology · 2025Review
- Marine sponge microbe provides insights into evolution and virulence of the tubercle bacillus.PLoS pathogens · 2024Article
- The whole genome sequence of Polish vaccine strainMicrobiology spectrum · 2024Article
- A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome.Nature communications · 2022Article
- In Silico Exploration ofBiomolecules · 2022Article
- TheInternational journal of molecular sciences · 2022Review
- In-depth Analysis of ISFrontiers in microbiology · 2022Article
- Identification of region of difference and H37Rv-related deletion inFrontiers in microbiology · 2022Article
- PE_PGRS3 ensures provision of the vital phospholipids cardiolipin and phosphatidylinositols by promoting the interaction betweenVirulence · 2021Article
- Article
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Tuberculosis is the deadliest infectious disease worldwide. Although the BCG vaccine is widely used, it does not efficiently protect against pulmonary tuberculosis and an improved tuberculosis vaccine is therefore urgently needed. Mycobacterium tuberculosis uses different ESX/Type VII secretion (T7S) systems to transport proteins important for virulence and host immune responses. We recently reported that secretion of T7S substrates belonging to the mycobacteria-specific Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins of the PGRS (polymorphic GC-rich sequences) and MPTR (major polymorphic tandem repeat) subfamilies required both a functional ESX-5 system and a functional PPE38/71 protein for secretion. Inactivation of ppe38/71 and the resulting loss of PE_PGRS/PPE-MPTR secretion were linked to increased virulence of M. tuberculosis strains. Here, we show that a predicted total of 89 PE_PGRS/PPE-MPTR surface proteins are not exported by certain animal-adapted strains of the M. tuberculosis complex including M. bovis. This Δppe38/71-associated secretion defect therefore also occurs in the M. bovis-derived tuberculosis vaccine BCG and could be partially restored by introduction of the M. tuberculosis ppe38-locus. Epitope mapping of the PPE-MPTR protein PPE10, further allowed us to monitor T-cell responses in splenocytes from BCG/M. tuberculosis immunized mice, confirming the dependence of PPE10-specific immune-induction on ESX-5/PPE38-mediated secretion. Restoration of PE_PGRS/PPE-MPTR secretion in recombinant BCG neither altered global antigenic presentation or activation of innate immune cells, nor protective efficacy in two different mouse vaccination-infection models. This unexpected finding stimulates a reassessment of the immunomodulatory properties of PE_PGRS/PPE-MPTR proteins, some of which are contained in vaccine formulations currently in clinical evaluation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.