Towards a paradigm shift in innate immunity—seminal work by Hans G. Boman and co-workers

Faye, Ingrid; Lindberg, Bo G.

doi:10.1098/rstb.2015.0303

Cited by 13 publications

(13 citation statements)

References 70 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since Hans Boman's discoveries in the 1970s [4], a vast and growing literature has unravelled many of the secrets of AMPs. We now have a much better understanding of their role and function.…”

Section: Discussionmentioning

confidence: 99%

“…In vertebrates [11] and to a lesser extent in crustaceans [17], AMPs are also immune-modulators and have anti-inflammatory properties or contribute to wound healing. Thus, while research on AMPs has mostly focused on their antimicrobial properties in the context of pathogens (a fact that might partly be ascribed to the history of their discovery [4]), in many multicellular organisms, AMPs have other functions. They can be important mediators of interactions with commensal or mutualistic bacteria, on both an ecological as well as evolutionary scale.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Perspectives on the evolutionary ecology of arthropod antimicrobial peptides

Rolff

Schmid‐Hempel

2016

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Antimicrobial peptides (AMPs) are important elements of the innate immune defence in multicellular organisms that target and kill microbes. Here, we reflect on the various points that are raised by the authors of the 11 contributions to a special issue of Philosophical Transactions on the 'evolutionary ecology of arthropod antimicrobial peptides'. We see five interesting topics emerging. (i) AMP genes in insects, and perhaps in arthropods more generally, evolve much slower than most other immune genes. One explanation refers to the constraints set by AMPs being part of a finely tuned defence system. A new view argues that AMPs are under strong stabilizing selection. Regardless, this striking observation still invites many more questions than have been answered so far. (ii) AMPs almost always are expressed in combinations and sometimes show expression patterns that are dependent on the infectious agent. While it is often assumed that this can be explained by synergistic interactions, such interactions have rarely been demonstrated and need to be studied further. Moreover, how to define synergy in the first place remains difficult and needs to be addressed. (iii) AMPs play a very important role in mediating the interaction between a host and its mutualistic or commensal microbes. This has only been studied in a very small number of (insect) species. It has become clear that the very same AMPs play different roles in different situations and hence are under concurrent selection. (iv) Different environments shape the physiology of organisms; especially the host-associated microbial communities should impact on the evolution host AMPs. Studies in social insects and some organisms from extreme environments seem to support this notion, but, overall, the evidence for adaptation of AMPs to a given environment is scant. (v) AMPs are considered or already developed as new drugs in medicine. However, bacteria can evolve resistance to AMPs. Therefore, in the light of our limited understanding of AMP evolution in the natural context, and also the very limited understanding of the evolution of resistance against AMPs in bacteria in particular, caution is recommended. What is clear though is that study of the ecology and evolution of AMPs in natural systems could inform many of these outstanding questions, including those related to medical applications and pathogen control.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Perspectives on the evolutionary ecology of arthropod antimicrobial peptides

Rolff

Schmid‐Hempel

2016

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

show abstract

“…The initial observation by Boman and colleagues that flies could mount a rapid antimicrobial response upon immune challenge launched the study of invertebrate AMPs, and Drosophila-related research was fundamental to the identification and study of the signalling pathways that mediate antimicrobial peptide gene expression [9,[24][25][26]. This work also established D. melanogaster as a model to study more broadly the molecular mechanisms of innate immunity, which has been important for informing our understanding of them in other animals.…”

Section: Drosophila Detection Of Microbes and Amp Productionmentioning

confidence: 97%

“…Though D. melanogaster rose to prominence nearly a 100 years ago as a model to study the genetics of heredity, mutations and development, it was not until the 1970s that D. melanogaster was adopted for the study of innate immunity [20,24]. The initial observation by Boman and colleagues that flies could mount a rapid antimicrobial response upon immune challenge launched the study of invertebrate AMPs, and Drosophila-related research was fundamental to the identification and study of the signalling pathways that mediate antimicrobial peptide gene expression [9,[24][25][26].…”

Section: Drosophila Detection Of Microbes and Amp Productionmentioning

confidence: 99%

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

Broderick

2016

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Drosophila melanogaster lives, breeds and feeds on fermenting fruit, an environment that supports a high density, and often a diversity, of microorganisms. This association with such dense microbe-rich environments has been proposed as a reason that D. melanogaster evolved a diverse and potent antimicrobial peptide (AMP) response to microorganisms, especially to combat potential pathogens that might occupy this niche. Yet, like most animals, D. melanogaster also lives in close association with the beneficial microbes that comprise its microbiota, or microbiome, and recent studies have shown that antimicrobial peptides (AMPs) of the epithelial immune response play an important role in dictating these interactions and controlling the host response to gut microbiota. Moreover, D. melanogaster also eats microbes for food, consuming fermentative microbes of decaying plant material and their by-products as both larvae and adults. The processes of nutrient acquisition and host defence are remarkably similar and use shared functions for microbe detection and response, an observation that has led to the proposal that the digestive and immune systems have a common evolutionary origin. In this manner, D. melanogaster provides a powerful model to understand how, and whether, hosts differentiate between the microbes they encounter across this spectrum of associations.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

show abstract

“…31, 32, 33, 34, 35, 36, 37, 38, 39 In mammals, HDPs are found within granules of neutrophils and in secretions from epithelial cells covering skin and mucosal surfaces. Their discovery can be traced to 1939, with the extraction of gramcidin from Bacillus brevis , followed, in the 1980s, by the isolation of cecropins in silk moths (Hyalophora) by Hans Boman 40 and magainins in frogs ( Xenopus laevis ) by Michael Zasloff. 41…”

Section: Introductionmentioning

confidence: 99%

Brilacidin, a COVID-19 Drug Candidate, Exhibits PotentIn VitroAntiviral Activity Against SARS-CoV-2

Bakovic

Risner

Bhalla

et al. 2020

Preprint

View full text Add to dashboard Cite

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than one million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin−a de novo designed synthetic small molecule that captures the biological properties of HDPs−on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is primarily a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin has demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 and thus supports brilacidin as a promising COVID-19 drug candidate. Highlights: Brilacidin potently inhibits SARS-CoV-2 in an ACE2 positive human lung cell line. Brilacidin achieved a high Selectivity Index of 426 (CC50=241µM/IC50=0.565µM). Brilacidin's main mechanism appears to disrupt viral integrity and impact viral entry. Brilacidin and remdesivir exhibit excellent synergistic activity against SARS-CoV-2. Significance Statement: SARS-CoV-2, the emergent novel coronavirus, has led to the current global COVID-19 pandemic, characterized by extreme contagiousness and high mortality rates. There is an urgent need for effective therapeutic strategies to safely and effectively treat SARS-CoV-2 infection. We demonstrate that brilacidin, a synthetic small molecule with peptide-like properties, is capable of exerting potent in vitro antiviral activity against SARS-CoV-2, both as a standalone treatment and in combination with remdesivir, which is currently the only FDA-approved drug for the treatment of COVID-19.

show abstract

Towards a paradigm shift in innate immunity—seminal work by Hans G. Boman and co-workers

Abstract: One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

Cited by 13 publications

References 70 publications

Perspectives on the evolutionary ecology of arthropod antimicrobial peptides

Perspectives on the evolutionary ecology of arthropod antimicrobial peptides

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

Brilacidin, a COVID-19 Drug Candidate, Exhibits PotentIn VitroAntiviral Activity Against SARS-CoV-2

Contact Info

Product

Resources

About