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Toxins (Basel). 2017 Sep 5;9(9). pii: E273. doi: 10.3390/toxins9090273.

Listeriolysin O Regulates the Expression of Optineurin, an Autophagy Adaptor That Inhibits the Growth of Listeria monocytogenes.

Author information

1
Institute of Medical Microbiology, Justus-Liebig University, 35392 Giessen, Germany. madhu.006.2009@gmail.com.
2
Institute of Medical Microbiology, Justus-Liebig University, 35392 Giessen, Germany. luigi.la-pietra@mikrobio.med.uni-giessen.de.
3
Institute of Medical Microbiology, Justus-Liebig University, 35392 Giessen, Germany. mobarak.mraheil@mikrobio.med.uni-giessen.de.
4
Vascular Biology Center, Department of Pharmacology and Toxicology and Division of Pulmonary and Critical Care Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. rlucas@augusta.edu.
5
Institute of Medical Microbiology, Justus-Liebig University, 35392 Giessen, Germany. trinad.chakraborty@mikrobio.med.uni-giessen.de.
6
Institute of Medical Microbiology, Justus-Liebig University, 35392 Giessen, Germany. helena.pillich@mikrobio.med.uni-giessen.de.

Abstract

Autophagy, a well-established defense mechanism, enables the elimination of intracellular pathogens including Listeria monocytogenes. Host cell recognition results in ubiquitination of L. monocytogenes and interaction with autophagy adaptors p62/SQSTM1 and NDP52, which target bacteria to autophagosomes by binding to microtubule-associated protein 1 light chain 3 (LC3). Although studies have indicated that L. monocytogenes induces autophagy, the significance of this process in the infectious cycle and the mechanisms involved remain poorly understood. Here, we examined the role of the autophagy adaptor optineurin (OPTN), the phosphorylation of which by the TANK binding kinase 1 (TBK1) enhances its affinity for LC3 and promotes autophagosomal degradation, during L. monocytogenes infection. In LC3- and OPTN-depleted host cells, intracellular replicating L. monocytogenes increased, an effect not seen with a mutant lacking the pore-forming toxin listeriolysin O (LLO). LLO induced the production of OPTN. In host cells expressing an inactive TBK1, bacterial replication was also inhibited. Our studies have uncovered an OPTN-dependent pathway in which L. monocytogenes uses LLO to restrict bacterial growth. Hence, manipulation of autophagy by L. monocytogenes, either through induction or evasion, represents a key event in its intracellular life style and could lead to either cytosolic growth or persistence in intracellular vacuolar structures.

KEYWORDS:

Listeria monocytogenes; autophagy; listeriolysin O; optineurin

PMID:
28872615
PMCID:
PMC5618206
DOI:
10.3390/toxins9090273
[Indexed for MEDLINE]
Free PMC Article

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