Circulating lethal toxin decreases the ability of neutrophils to respond to<i>B</i><i>acillus anthracis</i>

Weiner, Zachary P.; Ernst, Stephen M.; Boyer, Anne; Gallegos-Candela, Maribel; Barr, John R.; Glomski, Ian J.

doi:10.1111/cmi.12232

Cited by 23 publications

(36 citation statements)

References 60 publications

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“…Other in vivo studies have indicated that LT is capable of reducing chemotaxis to PMA mediated inflammation in the ear in mice models [184].…”

Section: Immunological Effectsmentioning

confidence: 97%

“…Therefore, it stands to reason that a swift influx of neutrophils is necessary to contain an infection by B. anthracis. Neutrophils play a key role in clearing B. anthracis infection and the exotoxin is capable of abrogating their protective effects [183][184][185]. Further, early production of pro-inflammatory cytokines, such as IL-1β, can increase host survival mediated by neutrophils [186].…”

Section: Immunological Effectsmentioning

confidence: 99%

“…Regardless of the route of infection, B. anthracis has a common method of dissemination ( Figure 3) [264,265]. Spores germinate in the initial site of the infection and the vegetative bacilli produce the exotoxin and capsule (Weiner et al, 2014). Within this initial site, also known as a portal of entry, the bacilli replicate and increase the exotoxin concentration in the local environment.…”

Section: Dissemination Of Bacillus Anthracis In the Hostmentioning

confidence: 99%

“…Within this initial site, also known as a portal of entry, the bacilli replicate and increase the exotoxin concentration in the local environment. From this portal of entry, bacilli disseminate to the draining lymphatics and repeat the process of replication and increase exotoxin concentration in the host [184] .…”

Section: Dissemination Of Bacillus Anthracis In the Hostmentioning

confidence: 99%

“…Deletion of CMG2/ANTXR2 in myeloid cells led to host resistance to infection with an uncapsulated strain in mice [183]. LF in particular is important for disabling the immune response early in infection [184]. In addition to targeting local immune cells at the initial site of infection, the exotoxin affects key tissues which contribute to the death of the animal [128].…”

Section: Introductionmentioning

confidence: 99%

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Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

Lowe

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Bacillus anthracis is a Gram positive sporulating bacterium that is the causative agent of anthrax. Early steps in dissemination are understudied due to the asymptomatic and asynchronous nature of B. anthracis infections. The goals of these studies are to establish a model of the early steps of B. anthracis infections and examine how the initial site of infection and exotoxin production affect bacterial dissemination. In these studies, a mouse model was used in combination with a bioluminescent signature tagged library to determine how B.anthracis disseminates through the host and the roles of an exotoxin component, lethal factor, in colonization and dissemination. This library allowed for real time observation of dissemination and analysis of bacterial population dynamics. In the first set of experiments, mice were infected via inhalational or subcutaneous routes with the tagged library to determine how the bacterial population changed during dissemination. In inhalational and subcutaneous infections, the disseminated population was comprised of a small subset of the original library.This indicated the presence of a population bottleneck, a random decrease in genetic diversity during the infection. Surprisingly, the diminishment and location of the bottleneck varied depending on the initial site of infection. This suggested B. anthracis exploits multiple host environments and some sites may be more permissive for dissemination than others. In the second set of experiments, mice were infected with a signature tagged library where a portion of clones lacked lethal factor. Lethal factor is known to be an important virulence factor as deletion results in attenuated or complete loss of virulence in most animal models. Host survival increased when < 10% of the library produced lethal factor, but few other differences were observed. Furthermore, decreases in the proportion of lethal factor producing clones led to fewer clones disseminating. These findings suggest that a threshold of lethal factor must be ii produced for colonization and dissemination to occur in vivo. In total, this work provides an understanding of how B. anthracis is able to rapidly disseminate from a several tissues and gives insights in where future therapeutics should be focused to reduce disease incidence.iii

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“…Other in vivo studies have indicated that LT is capable of reducing chemotaxis to PMA mediated inflammation in the ear in mice models [184].…”

Section: Immunological Effectsmentioning

confidence: 97%

Section: Immunological Effectsmentioning

confidence: 99%

Section: Dissemination Of Bacillus Anthracis In the Hostmentioning

confidence: 99%

Section: Dissemination Of Bacillus Anthracis In the Hostmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

Lowe

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In Vivo Bacterial Imaging Using Bioluminescence

Barbier

Bevere

Damron

2018

Methods in Molecular Biology

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Bacterial luminescence allows for noninvasive continuous monitoring of promoter activity in a wide range of model systems. This chapter details various examples of use of the lux reporter system to measure promoter activity in bacteria using the vector pUC18T-mini-Tn7T-lux-Tp. Here, we describe the construction of promoter fusions with bacterial luciferase, and how to quantify promoter activity in real time in vitro and in vivo in plant, insect, and murine infection models.

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