Role of the PE/PPE Family in Host–Pathogen Interactions and Prospects for Anti-Tuberculosis Vaccine and Diagnostic Tool Design

Qian, Jianing; Chen, Run; Wang, Honghai; Zhang, Xuelian

doi:10.3389/fcimb.2020.594288

Cited by 42 publications

(34 citation statements)

References 89 publications

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“…The proteomics data indicated that the mycomembrane-associated PPE/PE family proteins were remarkably greater in number in the PL cells than in the PBFs or SBFs, indicating that Mmr in a single-cell state could more readily interact with the host and modulate the host immune response and/or nutrient transport ( 49 , 50 ). PL cells were cultured in the presence of Tween 80, which, in detaching the mycobacterial capsule ( 17 ), most likely helped identify these immunogens.…”

Section: Discussionmentioning

confidence: 99%

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

et al. 2021

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Mycobacteria are naturally resilient, and mycobacterial infections are notoriously difficult to treat with antibiotics, with biofilm formation being the main factor complicating the successful treatment of tuberculosis (TB). The present study shows that nontuberculous Mycobacterium marinum ATCC 927 forms submerged- and pellicle-type biofilms with lichen- and ribbon-like structures, respectively, as well as persister cells under the same conditions.

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Section: Discussionmentioning

confidence: 99%

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

et al. 2021

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“…Previous studies on TB subunit vaccines have provided a large number of vaccine candidate antigens for peptide-based vaccines development, such as Ag85A (Rv3804c) ( 241 ), Ag85B (Rv1886c) ( 116 , 202 , 239 , 240 ), 6-kDa early secretory antigenic target (ESAT-6, Rv3875) ( 222 , 223 , 238 , 239 ), heat shock protein HspX (also known as Hsp16.3, Acr, and 14 kDa antigen, Rv2031c) ( 115 , 146 , 202 , 210 , 211 , 242 ), TB10.4 (Rv0288) ( 2 , 115 , 211 , 240 ), Rv0476 ( 211 ), Hsp65 ( 202 ), 19-kDa lipoprotein (Rv3763) ( 202 ), Rv1733c ( 202 , 203 ), PE/PPE proteins ( 2 , 243 , 244 , 248 ), MPT64 (Rv1980c) ( 246 , 247 ), Mtb8.4 ( 2 ), and resuscitation-promoting factors (Rpfs) ( 2 , 228 ). These antigens have been reported to be attractive vaccine candidates for preventing and controlling TB.…”

Section: Research Status Of Tb Peptide-based Vaccinesmentioning

confidence: 99%

Peptide-Based Vaccines for Tuberculosis

Gong

Pan²,

Cheng

et al. 2022

Front. Immunol.

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO’s End TB Strategy.

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“…The proteomics data indicated that the mycomembrane-associated PPE/PE family proteins were remarkably greater in number in the PL than in the PBFs or SBFs, indicating that Mmr in a single cell state could more readily interact with the host, and modulate the host immune response and/or nutrient transport (49, 50). PL cells were cultured in the presence of Tween-80, which, in detaching the mycobacterial capsule (17), most likely helped identify these immunogens.…”

Section: Discussionmentioning

confidence: 99%

Surface-Shaving Proteomics ofMycobacterium marinumIdentifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance and Persistence

Savijoki

Myllymäki

Luukinen

et al. 2021

Preprint

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The complex cell wall and biofilm matrix (ECM) act as key barriers to antibiotics in mycobacteria. Here, the ECM-proteins of Mycobacterium marinum ATCC927, a non-tuberculous mycobacterial model, was monitored over three months by label-free proteomics and compared with cell-surface proteins on planktonic cells to uncover pathways leading to virulence, tolerance, and persistence. We show that ATCC927 forms pellicle-type (PBFs) and submerged-type (SBFs) biofilms after two weeks and two days of growth, respectively, and that the increased CelA1 synthesis in this strain prevents biofilm formation and leads to reduced rifampicin tolerance. The proteomic data suggests that specific changes in mycolic acid synthesis (cord factor), Esx1-secretion, and cell-wall adhesins explain the appearance of PBFs as ribbon-like cords and SBFs as lichen-like structures. A subpopulation of cells resisting the 64 × MIC rifampicin (persisters) were detected in both biofilm subtypes, and already in one-week-old SBFs. The key forces boosting their development could include subtype-dependent changes in asymmetric cell division, cell wall biogenesis, tricarboxylic acid/glyoxylate cycle activities, and energy/redox/iron metabolisms. The effect of varying ambient oxygen tensions on each cell type and non-classical protein secretion are likely factors explaining majority of the subtype-specific changes. The proteomic findings also imply that Esx1-type protein secretion is more efficient in PL and PBF cells, while SBF may prefer both the Esx5- and non-classical pathways to control virulence and prolonged viability/persistence. In conclusion, this study reports a first proteomic insight into aging mycobacterial biofilm-ECMs and indicates biofilm subtype-dependent mechanisms conferring increased adaptive potential and virulence on non-tuberculous mycobacteria.IMPORTANCEMycobacteria are naturally resilient and mycobacterial infections are notoriously difficult to treat with antibiotics, with biofilm formation being the main factor complicating the successful treatment of TB. The present study shows that non-tuberculous Mycobacterium marinum ATCC927 forms submerged- and pellicle-type biofilms with lichen- and ribbon-like structures, respectively, as well as persister cells under the same conditions. We show that both biofilm subtypes differ in terms of virulence-, tolerance- and persistence-conferring activities, highlighting the fact that both subtypes should be targeted to maximize the power of antimycobacterial treatment therapies.

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Role of the PE/PPE Family in Host–Pathogen Interactions and Prospects for Anti-Tuberculosis Vaccine and Diagnostic Tool Design

Cited by 42 publications

References 89 publications

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence

Peptide-Based Vaccines for Tuberculosis

Surface-Shaving Proteomics ofMycobacterium marinumIdentifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance and Persistence

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