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

International Journal of Molecular Sciences

Fanny Wondany¹  Jens Michaelis¹  Dhruva Deshpande¹  Fabian Gerbl²  Mark Grieshober²  Reiner Noschka²  Steffen Stenger² 

[1] Institute of Biophysics, Ulm University, 89081 Ulm, Germany;Institute of Medical Microbiology and Hygiene, University Hospital Ulm, 89081 Ulm, Germany;

关键词: LL-37;    antimicrobial peptide;    Mycobacterium tuberculosis;    STED;    human macrophages;   

DOI  :  10.3390/ijms21186741

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown