Insect antimicrobial peptides act synergistically to inhibit a trypanosome parasite

Self 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'.

Section: Introductionmentioning

confidence: 99%

Perspectives on the evolutionary ecology of arthropod antimicrobial peptides

Rolff

Schmid‐Hempel

2016

Self Cite

“…This may suggest that they contribute to defence and/ or digestion in a form clearly distinct from the other microbeinducible effectors. These abf genes may thus also have a less prominent role as inducible immune effectors than the homologous defensin-like genes in arthropods (see [3,85,86] in this issue).…”

Section: Future Challenges: Functional Evidence For Worm Immune Effecmentioning

confidence: 99%

“…Effector molecules are usually studied in isolation, although several effector genes are simultaneously expressed in response to pathogen infection and some effector proteins are known to exert their antimicrobial activity in synergy with other immune effectors to enhance their potency ( [95]; see also [85,86,96]). Interestingly, the mixture of expressed effector genes seems to be highly specific (figures 2 and 3).…”

Section: Future Challenges: Functional Evidence For Worm Immune Effecmentioning

confidence: 99%

Antimicrobial effectors in the nematode Caenorhabditis elegans : an outgroup to the Arthropoda

Dierking

Yang

Schulenburg

2016

One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Nematodes and arthropods likely form the taxon Ecdysozoa. Information on antimicrobial effectors from the model nematode Caenorhabditis elegans may thus shed light on the evolutionary origin of these defences in arthropods. This nematode species possesses an extensive armory of putative antimicrobial effector proteins, such as lysozymes, caenopores (or saposin-like proteins), defensin-like peptides, caenacins and neuropeptide-like proteins, in addition to the production of reactive oxygen species and autophagy. As C. elegans is a bacterivore that lives in microbe-rich environments, some of its effector peptides and proteins likely function in both digestion of bacterial food and pathogen elimination. In this review, we provide an overview of C. elegans immune effector proteins and mechanisms. We summarize the experimental evidence of their antimicrobial function and involvement in the response to pathogen infection. We further evaluate the microbe-induced expression of effector genes using WormExp, a recently established database for C. elegans gene expression analysis. We emphasize the need for further analysis at the protein level to demonstrate an antimicrobial activity of these molecules both in vitro and in vivo.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

“…Hedges [16] developed the multi-hit model for AMPs but did not consider inhibitor combinations. However, combinations of AMPs are common in host-microbe interactions [4][5][6][7][8]. The vast majority of AMPs are cationic, hence mostly targeting bacterial cell membranes that are negatively charged.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, multiple AMPs are expressed in concert [4][5][6][7][8]. The co-expression is hypothesized to be due to synergy between AMPs [9,10].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

Baeder

Hozé

et al. 2016

One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.