The Pore-Forming Toxin Listeriolysin O Is Degraded by Neutrophil Metalloproteinase-8 and Fails To Mediate <i>Listeria monocytogenes</i> Intracellular Survival in Neutrophils

Arnett, Eusondia; Vadia, Stephen; Nackerman, Colleen C.; Oghumu, Steve; Satoskar, Abhay R.; McLeish, Kenneth R.; Uriarte, Silvia M.; Seveau, Stéphanie

doi:10.4049/jimmunol.1301302

Cited by 31 publications

(30 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preparation of all MARTX Vc and MARTX Ah constructs (Kudryashova et al, 2014), PA (Wesche et al, 1998), and CDC toxins [LLO, ALO, and PLY; (Arnett et al, 2014; Glomski et al, 2002)] was published. TcdA- and TcdB-GTD constructs were expressed in Bacillus megaterium cells (provided by Dr. Lacy; Vanderbilt University) and purified as described (Chumbler et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Human Defensins Facilitate Local Unfolding of Thermodynamically Unstable Regions of Bacterial Protein Toxins

et al. 2014

Self Cite

View full text Add to dashboard Cite

SUMMARY Defensins are short cationic, amphiphilic, cysteine-rich peptides that constitute the front line immune defense against various pathogens. In addition to exerting direct antibacterial activities, defensins inactivate several classes of unrelated bacterial exotoxins. To date, no coherent mechanism has been proposed that would explain defensins’ enigmatic efficiency towards various toxins. We showed that binding of neutrophil α-defensin HNP1 to affected bacterial toxins caused their local unfolding, potentiated their thermal melting and precipitation, exposed new regions for proteolysis, and increased susceptibility to collisional quenchers, without causing similar affects on tested mammalian structural and enzymatic proteins. Enteric α-defensin HD5 and β-defensin hBD2 shared similar toxin-unfolding effects with HNP1, albeit to different degrees. We propose that protein susceptibility to inactivation by defensins is contingent to their thermolability and conformational plasticity and that the defensin-induced unfolding is a key element in the general mechanism of toxin inactivation by human defensins.

show abstract

Section: Methodsmentioning

confidence: 99%

Human Defensins Facilitate Local Unfolding of Thermodynamically Unstable Regions of Bacterial Protein Toxins

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…The efficiency of escape depends upon the nature and activation status of the host cell, and can vary from phagosome to phagosome within the same cell. For example, LLO and the PLCs are less efficient in activated than resting macrophages and are unable to protect L. monocytogenes from intracellular killing in human neutrophils [108, 109]. In these examples, it appears that host cells can use various strategies to limit or even prevent vacuolar escape.…”

Section: Listeriolysin O Is An Intracellular Pore-forming Toxin With mentioning

confidence: 99%

“…Also, lysosomal cathepsin-D degrades LLO in murine fibroblasts and macrophages, limiting the efficiency of L. monocytogenes escape in cultured cells, and impacting the course of infection in a murine model of listeriosis [111]. A similar enzymatic process was recently proposed to exist in neutrophils in which the matrix metalloproteinase-8, stored in secondary granules, degrades LLO [109]. Also, the antimicrobial peptides, α -defensins, stored at high concentrations in neutrophil primary granules, inhibit LLO release from the bacterium in addition to blocking its activity [64, 65].…”

Section: Listeriolysin O Is An Intracellular Pore-forming Toxin With mentioning

confidence: 99%

Multifaceted Activity of Listeriolysin O, the Cholesterol-Dependent Cytolysin of Listeria monocytogenes

Seveau

2014

Subcellular Biochemistry

Self Cite

View full text Add to dashboard Cite

The cholesterol-dependent cytolysins (CDCs) are a large family of pore-forming toxins that are produced by numerous Gram-positive bacterial pathogens. These toxins are released in the extracellular environment as water-soluble monomers or dimers that bind to cholesterol-rich membranes and assemble into large pore complexes. Depending upon their concentration, the nature of the host cell and membrane (cytoplasmic or intracellular) they target, the CDCs can elicit many different cellular responses. Among the CDCs, listeriolysin O (LLO), which is a major virulence factor of the facultative intracellular pathogen Listeria monocytogenes, is involved in several stages of the intracellular lifecycle of the bacterium and displays unique characteristics. It has long been known that following L. monocytogenes internalization into host cells, LLO disrupts the internalization vacuole, enabling the bacterium to replicate into the host cell cytosol. LLO is then used by cytosolic bacteria to spread from cell to cell, avoiding bacterial exposure to the extracellular environment. Although LLO is continuously produced during the intracellular lifecycle of L. monocytogenes, several processes limit its toxicity to ensure the survival of infected cells. It was previously thought that LLO activity was limited to mediating vacuolar escape during bacterial entry and cell to cell spreading. This concept has been challenged by compelling evidence suggesting that LLO secreted by extracellular L. monocytogenes perforates the host cell plasma membrane, triggering important host cell responses. This chapter provides an overview of the well-established intracellular activity of LLO and the multiple roles attributed to LLO secreted by extracellular L. monocytogenes.

show abstract

“…monocytogenes internalization was shown to be significantly different when comparing MOIs of 1 and 10 amongst different studies [32]. Further, using the same approach, it was reported that the percentage of infected cells at 4 and 24 hpi depends on the MOI used to infect cells [30].…”

Section: Figure 1| Macromolecular Differences Between Cells Of Eukarymentioning

confidence: 94%

Omics in Aid of Host-pathogen Interaction Studies: A Bacterial Perspective

Fels¹,

Gevaert²,

Damme³

2017

Preprint

View full text Add to dashboard Cite

By providing useful tools to study host-pathogen interactions, next-generation omics has recently enabled the study of gene expression changes in both pathogen and infected host simultaneously. However, since great discriminative power is required to study pathogen and host simultaneously throughout the infection process, the depth of quantitative gene expression profiling has proven to be unsatisfactory when focusing on bacterial pathogens, thus preferentially requiring specific strategies or the development of novel methodologies based on complementary omics approaches. In this review, we focus on the difficulties encountered when making use of omics approaches to study bacterial pathogenesis. Besides, we review different omics strategies (i.e. transcriptomics, proteomics and secretomics) and their applications for studying interactions of pathogens with their host.

show abstract

The Pore-Forming Toxin Listeriolysin O Is Degraded by Neutrophil Metalloproteinase-8 and Fails To Mediate Listeria monocytogenes Intracellular Survival in Neutrophils

Cited by 31 publications

References 95 publications

Human Defensins Facilitate Local Unfolding of Thermodynamically Unstable Regions of Bacterial Protein Toxins

Human Defensins Facilitate Local Unfolding of Thermodynamically Unstable Regions of Bacterial Protein Toxins

Multifaceted Activity of Listeriolysin O, the Cholesterol-Dependent Cytolysin of Listeria monocytogenes

Omics in Aid of Host-pathogen Interaction Studies: A Bacterial Perspective

Contact Info

Product

Resources

About