Mycobacterial Lipids Orchestrate Infection Stage-Specific Remodeling of the Host Actin Cytoskeleton
- 1Indian Institute of Technology Bombay , , ,
Abstract
The actin cytoskeleton is a central target of host–pathogen interactions, yet how distinct microbial factors engage specific actin regulatory pathways remains poorly understood. Here, we show that mycobacterial envelope lipids directly modulate host actin dynamics through distinct molecular mechanisms. Using quantitative imaging and lipidomic analysis, we demonstrate that sulfoglycolipids (SL-1) and phenolic glycolipid-1 (PGL-1) promote actin depolymerization via cofilin-mediated severing, whereas phthiocerol dimycocerosate (PDIM) and trehalose dimycolate (TDM) induce actin polymerization through activation of the WASP–Arp2/3 pathway. These lipid-specific effects correspond to changes in lipid abundance across infection stages, linking cytoskeletal remodeling to temporal regulation of infection. Functionally, actin depolymerization enhances bacterial uptake or release depending on lipid context, while polymerization differentially impacts host cell entry and intracellular persistence. Together, our findings establish that mycobacterial lipids act as molecular determinants of cytoskeletal organization, engaging distinct actin regulatory pathways to shape infection dynamics.
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BibTeX
@article{mishra2026mycobacterial,
title = {{Mycobacterial Lipids Orchestrate Infection Stage-Specific Remodeling of the Host Actin Cytoskeleton}},
author = {Manjari Mishra and Saitali Laha Roy and Aishi Dasgupta and Anjana P. Menon and Shobhna Kapoor},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c07536},
url = {https://pubs.acs.org/acsodf/article/11/41/63563/5445745/Mycobacterial-Lipids-Orchestrate-Infection-Stage},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Mycobacterial Lipids Orchestrate Infection Stage-Specific Remodeling of the Host Actin Cytoskeleton
AU - Manjari Mishra
AU - Saitali Laha Roy
AU - Aishi Dasgupta
AU - Anjana P. Menon
AU - Shobhna Kapoor
PY - 2026
DA - 2026/10/07
JO - ACS Omega
DO - 10.1021/acsomega.6c07536
UR - https://pubs.acs.org/acsodf/article/11/41/63563/5445745/Mycobacterial-Lipids-Orchestrate-Infection-Stage
AB - The actin cytoskeleton is a central target of host–pathogen interactions, yet how distinct microbial factors engage specific actin regulatory pathways remains poorly understood. Here, we show that mycobacterial envelope lipids directly modulate host actin dynamics through distinct molecular mechanisms. Using quantitative imaging and lipidomic analysis, we demonstrate that sulfoglycolipids (SL-1) and phenolic glycolipid-1 (PGL-1) promote actin depolymerization via cofilin-mediated severing, whereas phthiocerol dimycocerosate (PDIM) and trehalose dimycolate (TDM) induce actin polymerization through activation of the WASP–Arp2/3 pathway. These lipid-specific effects correspond to changes in lipid abundance across infection stages, linking cytoskeletal remodeling to temporal regulation of infection. Functionally, actin depolymerization enhances bacterial uptake or release depending on lipid context, while polymerization differentially impacts host cell entry and intracellular persistence. Together, our findings establish that mycobacterial lipids act as molecular determinants of cytoskeletal organization, engaging distinct actin regulatory pathways to shape infection dynamics.
SN - 2470-1343
ER -