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

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Savijoki , K , Myllymäki , H , Luukinen , H , Paulamäki , L , Vanha-aho , L-M , Svorjova , A , Miettinen , I , Fallarero , A , Ihalainen , T O , Yli-Kauhaluoma , J , Nyman , T A & Parikka , M 2021 , ' Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence,Tolerance, and Persistence ' , mSystems , vol. 6 , no. 3 , ARTN e00500-21 . https://doi.org/10.1128/mSystems.00500-21

Title: Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence,Tolerance, and Persistence
Author: Savijoki, Kirsi; Myllymäki, Henna; Luukinen, Hanna; Paulamäki, Lauri; Vanha-aho, Leena-Maija; Svorjova, Aleksandra; Miettinen, Ilkka; Fallarero, Adyary; Ihalainen, Teemu O; Yli-Kauhaluoma, Jari; Nyman, Tuula A.; Parikka, Mataleena
Contributor organization: Division of Pharmaceutical Biosciences
Drug Research Program
Division of Pharmacology and Pharmacotherapy
Explorations of Anti Infectives
Pharmaceutical Design and Discovery group
Divisions of Faculty of Pharmacy
Jari Yli-Kauhaluoma / Principal Investigator
Division of Pharmaceutical Chemistry and Technology
Date: 2021-06-22
Language: eng
Number of pages: 23
Belongs to series: mSystems
ISSN: 2379-5077
DOI: https://doi.org/10.1128/mSystems.00500-21
URI: http://hdl.handle.net/10138/332948
Abstract: The complex cell wall and biofilm matrix (ECM) act as key barriers to antibiotics in mycobacteria. Here, the ECM and envelope proteins of Mycobacterium marinum ATCC 927, a nontuberculous mycobacterial model, were monitored over 3 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 ATCC 927 forms pellicle-type and submerged-type biofilms (PBFs and SBFs, respectively) after 2 weeks and 2 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 suggest 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 64x MIC rifampicin (persisters) was detected in both biofilm subtypes and already in 1-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 various ambient oxygen tensions on each cell type and nonclassical protein secretion are likely factors explaining the majority of the subtype-specific changes. The proteomic findings also imply that Esx1-type protein secretion is more efficient in planktonic (PL) and PBF cells, while SBF may prefer both the Esx5 and nonclassical pathways to control virulence and prolonged viability/persistence. In conclusion, this study reports the first proteomic insight into aging mycobacterial biofilm ECMs and indicates biofilm subtype-dependent mechanisms conferring increased adaptive potential and virulence of nontuberculous mycobacteria. IMPORTANCE 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 submergedand 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.
Subject: 317 Pharmacy
biofilm matrix
biofilms
cell surface proteomics
Mycobacterium marinum
persistence
tolerance
biofilm matrix
biofilms
cell surface proteomics
Mycobacterium marinum
persistence
tolerance
LACTOBACILLUS-CRISPATUS
RECURRENT TUBERCULOSIS
MOONLIGHTING PROTEINS
MYCOLIC ACIDS
GROWTH
GENE
PATHOGENESIS
SYNTHETASE
EVOLUTION
MEMBRANE
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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