Conference
Presentation_1_ESKAPEE pathogens newly released from biofilm residence by a targeted monoclonal are sensitized to killing by traditional antibiotics.zip
| العنوان: | Presentation_1_ESKAPEE pathogens newly released from biofilm residence by a targeted monoclonal are sensitized to killing by traditional antibiotics.zip |
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| المؤلفون: | Nikola Kurbatfinski, Cameron N. Kramer, Steven D. Goodman, Lauren O. Bakaletz |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Microbiology, Microbial Genetics, Microbial Ecology, Mycology, AMR, MRSA, humanized monoclonal antibody, DNABII proteins, tip-chimer peptide |
| الوصف: | Introduction The “silent” antimicrobial resistance (AMR) pandemic is responsible for nearly five million deaths annually, with a group of seven biofilm-forming pathogens, known as the ESKAPEE pathogens, responsible for 70% of these fatalities. Biofilm-resident bacteria, as they exist within the disease site, are canonically highly resistant to antibiotics. One strategy to counter AMR and improve disease resolution involves developing methods to disrupt biofilms. These methods aim to release bacteria from the protective biofilm matrix to facilitate their killing by antibiotics or immune effectors. Several laboratories working on such strategies have demonstrated that bacteria newly released from a biofilm display a transient phenotype of significantly increased susceptibility to antibiotics. Similarly, we developed an antibody-based approach for biofilm disruption directed against the two-membered DNABII family of bacterial DNA-binding proteins, which serve as linchpins to stabilize the biofilm matrix. The incubation of biofilms with α-DNABII antibodies rapidly collapses them to induce a population of newly released bacteria (NRel). Methods In this study, we used a humanized monoclonal antibody (HuTipMab) directed against protective epitopes of a DNABII protein to determine if we could disrupt biofilms formed by the high-priority ESKAPEE pathogens as visualized by confocal laser scanning microscopy (CLSM) and COMSTAT2 analysis. Then, we demonstrated the potentiated killing of the induced NRel by seven diverse classes of traditional antibiotics by comparative plate count. Results To this end, ESKAPEE biofilms were disrupted by 50%−79% using a single tested dose and treatment period with HuTipMab. The NRel of each biofilm were significantly more sensitive to killing than their planktonically grown counterparts (heretofore, considered to be the most sensitive to antibiotic-mediated killing), even when tested at a fraction of the MIC (1/250–1/2 MIC). Moreover, the bacteria that remained within the biofilms of two ... |
| نوع الوثيقة: | conference object |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/presentation/Presentation_1_ESKAPEE_pathogens_newly_released_from_biofilm_residence_by_a_targeted_monoclonal_are_sensitized_to_killing_by_traditional_antibiotics_zip/25225871 |
| DOI: | 10.3389/fmicb.2023.1202215.s001 |
| الاتاحة: | https://doi.org/10.3389/fmicb.2023.1202215.s001 https://figshare.com/articles/presentation/Presentation_1_ESKAPEE_pathogens_newly_released_from_biofilm_residence_by_a_targeted_monoclonal_are_sensitized_to_killing_by_traditional_antibiotics_zip/25225871 |
| Rights: | CC BY 4.0 |
| رقم الانضمام: | edsbas.EC7E7BF0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fmicb.2023.1202215.s001 |
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