Listeriolysin O regulates the expression of optineurin, an autophagy adaptor that inhibits the growth of Listeria monocytogenes

Madhu Puri, Luigi La Pietra, Mobarak Abu Mraheil, Rudolf Lucas, Trinad Chakraborty, Helena Pillich

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article number273
JournalToxins
Volume9
Issue number9
DOIs
StatePublished - Sep 5 2017

Fingerprint

Listeria
Autophagy
Listeria monocytogenes
Phosphotransferases
Growth
Phosphorylation
Microtubule-Associated Proteins
Pathogens
Light
Bacteria
Cells
Degradation
Listeriosis
Ubiquitination
Defense Mechanisms
Listeria monocytogenes hlyA protein
Life Style

Keywords

  • Autophagy
  • Listeria monocytogenes
  • Listeriolysin O
  • Optineurin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Listeriolysin O regulates the expression of optineurin, an autophagy adaptor that inhibits the growth of Listeria monocytogenes. / Puri, Madhu; La Pietra, Luigi; Mraheil, Mobarak Abu; Lucas, Rudolf; Chakraborty, Trinad; Pillich, Helena.

In: Toxins, Vol. 9, No. 9, 273, 05.09.2017.

Research output: Contribution to journalArticle

Puri, Madhu ; La Pietra, Luigi ; Mraheil, Mobarak Abu ; Lucas, Rudolf ; Chakraborty, Trinad ; Pillich, Helena. / Listeriolysin O regulates the expression of optineurin, an autophagy adaptor that inhibits the growth of Listeria monocytogenes. In: Toxins. 2017 ; Vol. 9, No. 9.
@article{ef397e1a4aac44bfb252d20097556bc6,
title = "Listeriolysin O regulates the expression of optineurin, an autophagy adaptor that inhibits the growth of Listeria monocytogenes",
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 = "Autophagy, Listeria monocytogenes, Listeriolysin O, Optineurin",
author = "Madhu Puri and {La Pietra}, Luigi and Mraheil, {Mobarak Abu} and Rudolf Lucas and Trinad Chakraborty and Helena Pillich",
year = "2017",
month = "9",
day = "5",
doi = "10.3390/toxins9090273",
language = "English (US)",
volume = "9",
journal = "Toxins",
issn = "2072-6651",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

TY - JOUR

T1 - Listeriolysin O regulates the expression of optineurin, an autophagy adaptor that inhibits the growth of Listeria monocytogenes

AU - Puri, Madhu

AU - La Pietra, Luigi

AU - Mraheil, Mobarak Abu

AU - Lucas, Rudolf

AU - Chakraborty, Trinad

AU - Pillich, Helena

PY - 2017/9/5

Y1 - 2017/9/5

N2 - 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.

AB - 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.

KW - Autophagy

KW - Listeria monocytogenes

KW - Listeriolysin O

KW - Optineurin

UR - http://www.scopus.com/inward/record.url?scp=85028987791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028987791&partnerID=8YFLogxK

U2 - 10.3390/toxins9090273

DO - 10.3390/toxins9090273

M3 - Article

C2 - 28872615

AN - SCOPUS:85028987791

VL - 9

JO - Toxins

JF - Toxins

SN - 2072-6651

IS - 9

M1 - 273

ER -