Assessment of antimicrobial peptide LL-37 as a post-exposure therapy to protect against respiratory tularemia in mice

Flick-Smith, Helen C.; Fox, Marc A.; Hamblin, Karleigh A.; Richards, Mark I.; Jenner, Dominic C.; Laws, Thomas R.; Phelps, Amanda; Taylor, Christopher E.; Harding, Sarah V.; Ulaeto, David O.; Atkins, Helen S.

doi:10.1016/j.peptides.2013.02.024

Cited by 11 publications

(18 citation statements)

References 32 publications

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“…In support, administration of a human neutrophil-derived defensin reduces bacterial load in the infected peritoneal cavity 24 h after infection in an experimental Klebsiella pneumoniae infection in mice [5]. Likewise, when administrating post-Francisella tularensis infection, the cathelicidin-derived peptide LL-37 protects against respiratory tularemia in a murine model [6]. As opposed to the mammalian immune system that activates both innate and adaptive immunities, lower animals such as insects rely almost solely on a panel of AMP against bacteria in environments where these pathogens strive and are abundant [7].…”

Section: Introductionmentioning

confidence: 93%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro-and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

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Section: Introductionmentioning

confidence: 93%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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“…Pneumonia can also develop; this is the most severe form of the disease and results from inhalation of the bacterium or direct inoculation of the lungs. 101 F. tularensis is regarded as a Category A bioterrorism agent as it is extremely infectious, requiring less than fifty viable infectious organisms to cause disease and as few as 10 in the most pathogenic of strains, 102 which means it could easily be disseminated throughout a human population. Furthermore, if exposure to the bacterium occurred via an aerosol, this would result in the more severe pneumonic forms of the disease which is associated with up to 35% mortality if left untreated.…”

Section: Plague (Yersinia Pestis)mentioning

confidence: 99%

“…This is used as a model in mice due to its similarities with the most pathogenic human strain of F. tularensis (Schu 54), and is known as the live vaccine strain (LVS). 101,103 Studies have revealed that LL-37 was found to possess microbicidal activity against F. novicida, interestingly to a greater extent than NA-CATH, a helical cathelicidin found in venom from the snake, Naja atra. LL-37 and NA-CATH demonstrated EC 50 values of 0.24 and 1.54 μg/ml, respectively.…”

Section: Plague (Yersinia Pestis)mentioning

confidence: 99%

Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections

Findlay

Proudfoot

Stevens

et al. 2016

Pathogens and Global Health

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Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required.

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“…These include, for example, recombinant cystatin 9 [254] and small compounds prepared by ligandand structure-based drug design [255]. Currently, promising moderate therapy against tularemia comprises the immunosuppressive and/or immunomodulatory effects of antimicrobial peptides, such as human cathelicidin LL-37 peptide, novel synthetic hybrids designed from cecropin A, magainin II, granulysin peptides, or specific fly antimicrobial peptides as are attacin, cecropin, drosocin and drosomycin from Drosophila melanogaster [256][257][258][259]. These positively charged antimicrobial peptides are capable to disrupt the negatively charged bacterial membrane and limit the proliferation of microbes.…”

Section: Treatmentmentioning

confidence: 99%

Putting the Jigsaw Together - A Brief Insight Into the Tularemia

Kubelková

Macela

2015

Open Life Sciences

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Tularemia is a debilitating febrile and potentially fatal zoonotic disease of humans and other vertebrates caused by the Gram-negative bacterium Francisella tularensis. The natural reservoirs are small rodents, hares, and possibly amoebas in water. The etiological agent, Francisella tularensis, is a non-spore forming, encapsulated, facultative intracellular bacterium, a member of the γ-Proteobacteria class of Gram-negative bacteria. Francisella tularensis is capable of invading and replicating within phagocytic as well as non-phagocytic cells and modulate inflammatory response. Infection by the pulmonary, dermal, or oral routes, respectively, results in pneumonic, ulceroglandular, or oropharyngeal tularemia. The highest mortality rates are associated with the pneumonic form of this disease. All members of Francisella tularensis species cause more or less severe disease Due to their abilities to be transmitted to humans via multiple routes and to be disseminated via biological aerosol that can cause the disease after inhalation of even an extremely low infectious dose, Francisella tularensis has been classified as a Category A bioterrorism agent. The current standard of care for tularemia is treatment with antibiotics, as this therapy is highly effective if used soon after infection, although it is not, however, absolutely effective in all cases.

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Assessment of antimicrobial peptide LL-37 as a post-exposure therapy to protect against respiratory tularemia in mice

Cited by 11 publications

References 32 publications

Immunomodulatory effects of anti-microbial peptides

Immunomodulatory effects of anti-microbial peptides

Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections

Putting the Jigsaw Together - A Brief Insight Into the Tularemia

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