Listeriolysin O: from bazooka to Swiss army knife

By modifying the host cell transcription programme, pathogenic bacteria disrupt a wide range of cellular processes and take control of the host's immune system. Conversely, by mobilising a network of defence genes, the host cells trigger various responses that allow them to tolerate or eliminate invaders. The study of the molecular basis of this crosstalk is crucial to the understanding of infectious diseases. Although research has long focused on the targeting of eukaryotic DNA‐binding transcription factors, more recently, another powerful way by which bacteria modify the expression of host genes has emerged: chromatin modifications in the cell nucleus. One of the most prolific bacterial models in this area has been Listeria monocytogenes, a facultative intracellular bacterium responsible for serious food‐borne infections. Here, we aim to highlight the contribution of this model to the field of bacteria‐mediated chromatin modifications. We will first recall the general principles of epigenetic regulation and then illustrate five mechanisms that mobilise the epigenetic machinery in response to Listeria factors, either through bacterial molecular patterns, a toxin, an invasion protein, or nucleomodulins. Strategies used by Listeria to control the expression of host genes at the chromatin level, by activation of cytosolic signalling pathways or direct targeting of epifactors in the nucleus, have contributed to the emergence of a new discipline combining cellular microbiology and epigenetics: “patho‐epigenetics.”

Section: Toxin-induced Signalling Pathwaysmentioning

confidence: 99%

Targeting host epigenetic machinery: TheListeriaparadigm

Bierne

Hamon

2020

“…These responses are usually common to membrane insult by a range of PFTs and are often the direct result of Ca 2+ influx and/or K + efflux. As a result of these numerous and diverse effects, LLO has been called the "Swiss-army knife of Listeria" (Hamon, Ribet, Stavru, & Cossart, 2012;Osborne & Brumell, 2017). However, the role of these cellular responses in pathogenesis is not clear.…”

Section: Cellular Responses To Cdc-mediated Pore Formationmentioning

confidence: 99%

Listeriolysin O: A phagosome-specific cytolysin revisited

Nguyen

Peterson

Portnoy

2019

Listeriolysin O (LLO) is an essential determinant of Listeria monocytogenes pathogenesis that mediates the escape of L. monocytogenes from host cell vacuoles, thereby allowing replication in the cytosol without causing appreciable cell death. As a member of the cholesterol‐dependent cytolysin (CDC) family of pore‐forming toxins, LLO is unique in that it is secreted by a facultative intracellular pathogen, whereas all other CDCs are produced by pathogens that are largely extracellular. Replacement of LLO with other CDCs results in strains that are extremely cytotoxic and 10,000‐fold less virulent in mice. LLO has structural and regulatory features that allow it to function intracellularly without causing cell death, most of which map to a unique N‐terminal region of LLO referred to as the proline, glutamic acid, serine, threonine (PEST)‐like sequence. Yet, while LLO has unique properties required for its intracellular site of action, extracellular LLO, like other CDCs, affects cells in a myriad of ways. Because all CDCs form pores in cholesterol‐containing membranes that lead to rapid Ca2+ influx and K+ efflux, they consequently trigger a wide range of host cell responses, including mitogen‐activated protein kinase activation, histone modification, and caspase‐1 activation. There is no debate that extracellular LLO, like all other CDCs, can stimulate multiple cellular activities, but the primary question we wish to address in this perspective is whether these activities contribute to L. monocytogenes pathogenesis.

“…LLO triggers vacuolar rupture in most cells but promotes phagosomal replication in some macrophages (Birmingham et al, ). It acts extracellularly on host plasma membranes, promoting Ca 2+ influx in target cells (Dramsi & Cossart, ) and affecting many cell biological processes in host cells such as reactive oxygen species production, lysosomal permeabilization, activation of host signalling and inflammasome, apoptosis, autophagy, endoplasmic reticulum stress and cytokine secretion (Hamon et al, ; Osborne & Brumell, ). MS‐based proteomics combined with Stable Isotope Labeling of Amino acids in Cell culture (SILAC) provided a comprehensive view on protein‐level alterations in HeLa cells treated with LLO.…”

Section: Listeria Excellence In Manipulating Cellular Processesmentioning

confidence: 99%

“…For details, see Jasnin et al (2013) cells but promotes phagosomal replication in some macrophages (Birmingham et al, 2008). It acts extracellularly on host plasma membranes, promoting Ca 2+ influx in target cells (Dramsi & Cossart, 2003) and affecting many cell biological processes in host cells such as reactive oxygen species production, lysosomal permeabilization, activation of host signalling and inflammasome, apoptosis, autophagy, endoplasmic reticulum stress and cytokine secretion (Hamon et al, 2012;Osborne & Brumell, 2017) cell pathways, they are involved in many crucial steps of the infection process including pathogen entry, replication, propagation or detection by the host. Not surprisingly, many bacterial pathogens have developed strategies to interfere with host ubiquitin and UBL systems, either by global dampening of these systems or by altering the modification levels of specific host proteins involved in bacterial proliferation and antibacterial responses (extensively reviewed in .…”

Section: Besides Its Role In Bacterial Internalisation Actin Is Essementioning

confidence: 99%

Three decades of listeriology through the prism of technological advances

Impens

Dussurget

2020

Decades of breakthroughs resulting from cross feeding of microbiological research and technological innovation have promoted Listeria monocytogenes to the rank of model microorganism to study host–pathogen interactions. The extraordinary capacity of this bacterium to interfere with a vast array of host cellular processes uncovered new concepts in microbiology, cell biology and infection biology. Here, we review technological advances that revealed how bacteria and host interact in space and time at the molecular, cellular, tissue and whole body scales, ultimately revolutionising our understanding of Listeria pathogenesis. With the current bloom of multidisciplinary integrative approaches, Listeria entered a new microbiology era.