Cecropins contribute to Drosophila host defense against a subset of fungal and Gram-negative bacterial infection

Cecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding cecropins are strongly induced upon infection, pointing to their role in host-defense. In Drosophila, four cecropin genes clustered in the genome (CecA1, CecA2, CecB and CecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletion ΔCecA-C removing the whole cecropin locus. Using the ΔCecA-C deficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of cecropins in the systemic immune response. ΔCecA-C flies were viable and resisted challenge with various microbes as wild-type. However, removing ΔCecA-C in flies already lacking ten other AMP genes revealed a role for cecropins in defense against Gram-negative bacteria and fungi. Measurements of pathogen loads confirm that cecropins contribute to the control of certain Gram-negative bacteria, notably Enterobacter cloacae and Providencia heimbachae. Collectively, our work provides the first genetic demonstration of a role for cecropins in insect host defense, and confirms their in vivo activity primarily against Gram-negative bacteria and fungi. Generation of a fly line (ΔAMP14) that lacks fourteen immune inducible AMPs provides a powerful tool to address the function of these immune effectors in host-pathogen interactions and beyond.

Catestatin selects for the colonization of antimicrobial-resistant gut bacterial communities

The gut microbiota is in continuous interaction with the innermost layer of the gut, namely the epithelium. Among the various functions of the gut epithelium, is to keep the microbes at bay to avoid overstimulation of the underlying mucosa immune cells. To do so, the gut epithelia secrete a variety of antimicrobial peptides, such as catestatin (CST). As a defense mechanism, gut microbes have evolved antimicrobial resistance mechanisms to counteract the killing effect of the secreted peptides. To this end, we treated wild-type mice and mice with a knockout in the CST coding region of the chromogranin-A gene (CST-KO) with CST for 15 consecutive days. CST treatment was associated with a shift in the diversity and composition of the microbiota in the CST-KO mice. This effect was less prominent in WT mice. Levels of the microbiota-produced short-chain fatty acids, in particular, butyrate and acetate were significantly increased in CST-treated CST-KO mice but not the WT group. Remarkably, both CST-treated CST-KO and WT mice showed a significant increase in microbiota-harboring phosphoethanolamine transferase-encoding genes, which facilitate their antimicrobial resistance. Finally, we show that CST was degraded by Escherichia coli via an omptin-protease and that the abundance of this gene was significantly higher in metagenomic datasets collected from patients with Crohn's disease but not with ulcerative colitis. Overall, this study illustrates how the endogenous antimicrobial peptide, CST, shapes the microbiota composition in the gut and primes further research to uncover the role of bacterial resistance to CST in disease states such as inflammatory bowel disease.

Lymphatic Filariasis: An Immunologic Perspective

Introduction: This paper provides an overview of the current immunologic research findings of lymphatic filarial worms, which affect millions of people worldwide. Objectives: This paper aims to discuss the immunologic features of lymphatic filarial worms. It also aims to highlight their potential anti-inflammatory actions and the use of anti-filarial drugs against COVID-19. Methods: A literature review was performed to obtain insights on the immunologic features of lymphatic filarial worms. Results: The CD4+ (Th2) response profile is the main defence against filarial worms. Modulation of human immune responses are primarily mediated by parasite-secreted peptides. Lymphatic filarial worms have anti-inflammatory potentials. Drug repurposing of diethylcarbamazepine, doxycycline, and ivermectin can be looked upon against COVID-19. Conclusion: Lymphatic filarial worms have several immunologic effects on host immune systems, which promote chronic infection and curtail anti-inflammatory responses. Insights in this paper can serve as a guide for the understanding of immunologic aspects of lymphatic filarial worms.

Utilizing Developmentally Essential Secreted Peptides Such As Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State—New Directions in Anti-Aging Regenerative Therapies

Our dream of defeating the processes of aging has occupied the curious and has challenged scientists globally for hundreds of years. The history is long, and sadly, the solution is still elusive. Our endeavors to reverse the magnitude of damaging cellular and molecular alterations resulted in only a few, yet significant advancements. Furthermore, as our lifespan increases, physicians are facing more mind-bending questions in their routine practice than ever before. Although the ultimate goal is to successfully treat the body as a whole, steps towards regenerating individual organs are even considered significant. As our initial approach to enhance the endogenous restorative capacity by delivering exogenous progenitor cells appears limited, we propose, utilizing small molecules critical during embryonic development may prove to be a powerful tool to increase regeneration and to reverse the processes associated with aging. In this review, we introduce Thymosin beta-4, a 43aa secreted peptide fulfilling our hopes and capable of numerous regenerative achievements via systemic administration in the heart. Observing the broad capacity of this small, secreted peptide, we believe it is not the only molecule which nature conceals to our benefit. Hence, the discovery and postnatal administration of developmentally relevant agents along with other approaches may result in reversing the aging process.

Comparative analyses of angiosperm secretomes identify apoplastic pollen tube functions and novel secreted peptides

Key message Analyses of secretomes of in vitro grown pollen tubes from Amborella, maize and tobacco identified many components of processes associated with the cell wall, signaling and metabolism as well as novel small secreted peptides. Abstract Flowering plants (angiosperms) generate pollen grains that germinate on the stigma and produce tubes to transport their sperm cells cargo deep into the maternal reproductive tissues toward the ovules for a double fertilization process. During their journey, pollen tubes secrete many proteins (secreted proteome or secretome) required, for example, for communication with the maternal reproductive tissues, to build a solid own cell wall that withstands their high turgor pressure while softening simultaneously maternal cell wall tissue. The composition and species specificity or family specificity of the pollen tube secretome is poorly understood. Here, we provide a suitable method to obtain the pollen tube secretome from in vitro grown pollen tubes of the basal angiosperm Amborella trichopoda (Amborella) and the Poaceae model maize. The previously published secretome of tobacco pollen tubes was used as an example of eudicotyledonous plants in this comparative study. The secretome of the three species is each strongly different compared to the respective protein composition of pollen grains and tubes. In Amborella and maize, about 40% proteins are secreted by the conventional “classic” pathway and 30% by unconventional pathways. The latter pathway is expanded in tobacco. Proteins enriched in the secretome are especially involved in functions associated with the cell wall, cell surface, energy and lipid metabolism, proteolysis and redox processes. Expansins, pectin methylesterase inhibitors and RALFs are enriched in maize, while tobacco secretes many proteins involved, for example, in proteolysis and signaling. While the majority of proteins detected in the secretome occur also in pollen grains and pollen tubes, and correlate in the number of mapped peptides with relative gene expression levels, some novel secreted small proteins were identified. Moreover, the identification of secreted proteins containing pro-peptides indicates that these are processed in the apoplast. In conclusion, we provide a proteome resource from three distinct angiosperm clades that can be utilized among others to study the localization, abundance and processing of known secreted proteins and help to identify novel pollen tube secreted proteins for functional studies.

The cell fate controlling CLE40 peptide requires CNGC9 to trigger highly localized Ca2+ transients in Arabidopsis thaliana root meristems

Communication between plant cells and their biotic environment is largely dependent on the function of plasma membrane localized receptor-like kinases (RLKs). Major players in this communication within root meristems are secreted peptides, including CLAVATA3/EMBRYO SURROUNDING REGION40 (CLE40). In the distal root meristem, CLE40 acts through the receptor like kinase (RLK) ARABIDOPSIS CRINKLY4 (ACR4) and the leucine-rich repeat (LRR) RLK CLAVATA1 (CLV1) to promote cell differentiation. In the proximal meristem, CLE40 signalling requires the LRR receptor-like protein (RLP) CLAVATA2 (CLV2) and the membrane localized pseudokinase CORYNE (CRN), and serves to inhibit cell differentiation. The molecular components that act immediately downstream of the CLE40-activated receptors are not yet known. Here we show that active CLE40 signalling triggers the release of intracellular Ca2+ leading to increased cytosolic Ca2+ concentration ([Ca2+]cyt) in a subset of proximal root meristem cells. This rise in [Ca2+]cyt depends on the CYCLIC NUCLEOTIDE GATED CHANNEL 9 (CNGC9), CLV1, the CLV1-related BARELY ANY MERISTEM1 (BAM1), CLV2 and CRN. The precise function of changes in [Ca2+]cyt are not yet known, but might form a central part of a fine-tuned response to CLE40 peptide that serves to integrate root meristem growth with stem cell fate decisions and initiation of lateral root primordia.