Biology subjects

Parikka, M.

Publications and source records attributed to Parikka, M..

3 recordsLinked to original sources

bioRxiv2025

Hyperthermia reduces antimicrobial tolerance of Mycobacterium marinum in biofilms and ex vivo zebrafish granulomas

The treatment of tuberculosis (TB) is slow and inefficient. One suggested reason for the treatment difficulties are drug-tolerant biofilms that have been shown to develop in TB patients and animal models. In this pioneering pilot study, we explored the potential of hyperthermia in sensitizing biofilm-associated tolerant mycobacteria to antimicrobial agents. As the starting point, we used our newly-developed in vitro biofilm minimum duration for killing (MDK) tolerance assay for screening hyperthermal treatments of bioluminescent mycobacteria. Using standard plating methods, we verify that the combination of hyperthermia at 47{degrees}C for 30 minutes and an antimicrobial drug rifampicin at 400 g/ml has positive effects against cultured Mycobacterium marinum biofilms as well as M. marinum from granulomas isolated from adult zebrafish with chronic-stage infection. These intriguing findings suggest that hyperthermia could be used to enhance conventional TB treatments. Author SummaryTuberculosis (TB) and similar infections are hard to cure because the bacteria can "hide" from antibiotics. They do this by entering a state where they tolerate drugs without becoming resistant, often forming biofilms--sticky clusters that protect them from treatment. This makes therapy long and relapse common. We asked whether heat could help break this tolerance. Using a new lab test, we combined heat at different durations and temperatures with antibiotics against Mycobacterium marinum, a close relative of the TB bacterium. Heating made the antibiotic rifampicin much more effective, both in biofilms and in infected tissue from zebrafish, which mimic TB-like lesions. We saw similar benefits in TB bacteria when heat was paired with streptomycin. These results suggest that controlled heating could work alongside standard drugs to kill stubborn bacteria faster. Because heat damages cells in a general way, not by targeting one molecule, it might also reduce the risk of antibiotic resistance

microbiology↗

bioRxiv2024

Mechanistic modeling of Mycobacterium tuberculosis β-carbonic anhydrase inhibitors using integrated systems biology and the QSAR approach

Withdrawal StatementThe authors have withdrawn their manuscript owing to the inability to complete the revisions or follow up on the manuscript at this time, due to personal circumstances. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

bioinformatics↗

bioRxiv2021

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

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 x 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.

microbiology↗