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Super-Resolution Microscopy Reveals a Direct Interaction of Intracellular Mycobacterium tuberculosis with the Antimicrobial Peptide LL-37.


ABSTRACT: The antimicrobial peptide LL-37 inhibits the growth of the major human pathogen Mycobacterium tuberculosis (Mtb), but the mechanism of the peptide-pathogen interaction inside human macrophages remains unclear. Super-resolution imaging techniques provide a novel opportunity to visualize these interactions on a molecular level. Here, we adapt the super-resolution technique of stimulated emission depletion (STED) microscopy to study the uptake, intracellular localization and interaction of LL-37 with macrophages and virulent Mtb. We demonstrate that LL-37 is internalized by both uninfected and Mtb infected primary human macrophages. The peptide localizes in the membrane of early endosomes and lysosomes, the compartment in which mycobacteria reside. Functionally, LL-37 disrupts the cell wall of intra- and extracellular Mtb, resulting in the killing of the pathogen. In conclusion, we introduce STED microscopy as an innovative and informative tool for studying host-pathogen-peptide interactions, clearly extending the possibilities of conventional confocal microscopy.

SUBMITTER: Deshpande D 

PROVIDER: S-EPMC7555347 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Super-Resolution Microscopy Reveals a Direct Interaction of Intracellular <i>Mycobacterium tuberculosis</i> with the Antimicrobial Peptide LL-37.

Deshpande Dhruva D   Grieshober Mark M   Wondany Fanny F   Gerbl Fabian F   Noschka Reiner R   Michaelis Jens J   Stenger Steffen S  

International journal of molecular sciences 20200914 18


The antimicrobial peptide LL-37 inhibits the growth of the major human pathogen <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), but the mechanism of the peptide-pathogen interaction inside human macrophages remains unclear. Super-resolution imaging techniques provide a novel opportunity to visualize these interactions on a molecular level. Here, we adapt the super-resolution technique of stimulated emission depletion (STED) microscopy to study the uptake, intracellular localization and interacti  ...[more]

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