Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 7, Pages E687-E692Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1423318112
Keywords
autophagy; Dictyostelium discoideum; Mycobacterium marinum; ejection
Categories
Funding
- Leibniz Society
- Deutsche Forschungsgemeinschaft (DFG) [HA3474/3-1]
- Ciencia sem fronteiras (CsF) [BEX2607-13-1]
- Cancer Research-UK
- Royal Society Research Grant [RG130655]
- Swiss National Science Foundation
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In contrast to mechanisms mediating uptake of intracellular bacterial pathogens, bacterial egress and cell-to-cell transmission are poorly understood. Previously, we showed that the transmission of pathogenic mycobacteria between phagocytic cells also depends on nonlytic ejection through an F-actin based structure, called the ejectosome. How the host cell maintains integrity of its plasma membrane during the ejection process was unknown. Here, we reveal an unexpected function for the autophagic machinery in nonlytic spreading of bacteria. We show that ejecting mycobacteria are escorted by a distinct polar autophagocytic vacuole. If autophagy is impaired, cell-to-cell transmission is inhibited, the host plasma membrane becomes compromised and the host cells die. These findings highlight a previously unidentified, highly ordered interaction between bacteria and the autophagic pathway and might represent the ancient way to ensure nonlytic egress of bacteria.
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