2018

DOI: 10.1016/j.gene.2018.07.005

|View full text |Cite

|

Sign up to set email alerts

|

The novel cathelicidin of naked mole rats, Hg-CATH, showed potent antimicrobial activity and low cytotoxicity

¹

,

Nagasundarapandian Soundrarajan

²

,

Quy Le Van Chanh

³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Discussion2

Introduction2

In Silico Identification Of Amp-like Sequences From the Geno1

Citation Types

Supporting

1

Mentioning

19

Contrasting

1

Year Published

2019

2019

2022

2022

Publication Types

Select...

Article5

Preprint1

Book1

Relationship

Self Cite2

Independent5

Authors

Journals

Cited by 16 publications

(21 citation statements)

References 38 publications

Supporting

1

Mentioning

19

Contrasting

1

Order By: Relevance

“…Our data show that the naked mole-rat has a higher proportion of myeloid cells, abundance of Cd14 expression, and a seemingly unique population of LPS-responsive neutrophil-like cells with high expression of genes that encode anti-bacterial peptides. Further, although the naked mole-rat genome is not replete with an unusually large number of genes that encode antimicrobial peptide products, those that have been studied show potent antimicrobial activity (37). Taken together, these findings suggest that the naked mole-rat immune system has evolved under stronger anti-bacterial than anti-viral immune selective pressure.…”

Section: Discussionmentioning

confidence: 98%

Single-cell transcriptomics of the naked mole-rat reveals unexpected features of mammalian immunity

¹

,

²

,

³

et al. 2019

Preprint

View full text Add to dashboard Cite

Using single-cell transcriptional profiling we mapped the immune system of the naked mole-rat (Heterocephalus glaber), a small but long-lived and cancer-resistant subterranean rodent. Both splenic and circulating immune cells were examined in healthy young animals and following an infection-mimicking lipopolysaccharide challenge. Our study revealed that the naked mole-rat immune system is characterized by a high myeloid to lymphoid cell ratio that includes a novel, lipopolysaccharide responsive, granulocyte cell subset not found in the mouse. Conversely, we find that naked mole-rats do not have a cell subset that corresponds to natural killer cells as defined in other well-characterized mammalian species. Supporting this finding, we show that the naked mole-rat genome has not expanded any of the gene families encoding diverse natural killer cell receptors, which are the genomic hallmarks of species in which natural killer cells have been described. These unusual features suggest an atypical mode of immunosurveillance and a greater reliance on myeloid-biased innate immunity. 0

“…Our data show that the naked mole-rat has a higher proportion of myeloid cells, abundance of Cd14 expression, and a seemingly unique population of LPS-responsive neutrophil-like cells with high expression of genes that encode anti-bacterial peptides. Further, although the naked mole-rat genome is not replete with an unusually large number of genes that encode antimicrobial peptide products, those that have been studied show potent antimicrobial activity (37). Taken together, these findings suggest that the naked mole-rat immune system has evolved under stronger anti-bacterial than anti-viral immune selective pressure.…”

Section: Discussionmentioning

confidence: 98%

Single-cell transcriptomics of the naked mole-rat reveals unexpected features of mammalian immunity

¹

,

²

,

³

et al. 2019

Preprint

View full text Add to dashboard Cite

Using single-cell transcriptional profiling we mapped the immune system of the naked mole-rat (Heterocephalus glaber), a small but long-lived and cancer-resistant subterranean rodent. Both splenic and circulating immune cells were examined in healthy young animals and following an infection-mimicking lipopolysaccharide challenge. Our study revealed that the naked mole-rat immune system is characterized by a high myeloid to lymphoid cell ratio that includes a novel, lipopolysaccharide responsive, granulocyte cell subset not found in the mouse. Conversely, we find that naked mole-rats do not have a cell subset that corresponds to natural killer cells as defined in other well-characterized mammalian species. Supporting this finding, we show that the naked mole-rat genome has not expanded any of the gene families encoding diverse natural killer cell receptors, which are the genomic hallmarks of species in which natural killer cells have been described. These unusual features suggest an atypical mode of immunosurveillance and a greater reliance on myeloid-biased innate immunity. 0

“…Signal peptides and CLDs were determined using SignalP 4.1 server 4 (26) and HMMER 5 (27), respectively. DBAASP 6 (28) and Antimicrobial Sequence Scanning System (AMPA 7 ) (29) were used to predict potential antimicrobial activity using the default threshold. Protein secondary structures were analyzed using the PSIPRED protein sequence analysis workbench 8 .…”

Section: In Silico Identification Of Amp-like Sequences From the Genomentioning

confidence: 99%

“…The identification and characterization of endogenous AMPs has been limited to only a few species. However, the availability of genome sequences from diverse species along with AMP databases and bioinformatic tools facilitates the identification of novel AMPs (5,6).…”

Section: Introductionmentioning

confidence: 99%

Opossum Cathelicidins Exhibit Antimicrobial Activity Against a Broad Spectrum of Pathogens Including West Nile Virus

¹

,

²

,

³

et al. 2020

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

This study aimed to characterize cathelicidins from the gray short-tailed opossum in silico and experimentally validate their antimicrobial effects against various pathogenic bacteria and West Nile virus (WNV). Genome-wide in silico analysis against the current genome assembly of the gray short-tailed opossum yielded 56 classical antimicrobial peptides (AMPs) from eight different families, among which 19 cathelicidins, namely ModoCath1-19, were analyzed in silico to predict their antimicrobial domains and three of which, ModoCath1,-5, and-6, were further experimentally evaluated for their antimicrobial activity, and were found to exhibit a wide spectrum of antimicroial effects against a panel of gram-positive and gram-negative bacterial strains. In addition, these peptides displayed low-to-moderate cytotoxicity in mammalian cells as well as stability in serum and various salt and pH conditions. Circular dichroism analysis of the spectra resulting from interactions between ModoCaths and lipopolysaccharides (LPS) showed formation of a helical structure, while a dual-dye membrane disruption assay and scanning electron microscopy analysis revealed that ModoCaths exerted bactericidal effects by causing membrane damage. Furthermore, ModoCath5 displayed potent antiviral activity against WNV by inhibiting viral replication, suggesting that opossum cathelicidins may serve as potentially novel antimicrobial endogenous substances of mammalian origin, considering their large number. Moreover, analysis of publicly available RNA-seq data revealed the expression of eight ModoCaths from five different tissues, suggesting that gray short-tailed opossums may be an interesting source of cathelicidins with diverse characteristics.

“…Not all AMPs exert severe cytotoxic effects in mammalian cells 10,11 . However, understanding the underlying mechanism allows for a window to rationally design AMPs to reduce their cytotoxicity which is a very important factor for their therapeutic application.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the growing incidence of antibiotic resistant bacteria has become a big concern in the health care industry 7 , and AMPs are being exploited as alternatives or combinatorial candidates with antibiotics to combat such pathogens 8,9 . The availability of genome sequences from diverse species also provides increased opportunities for the discovery of new AMPs 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Protegrin-1 cytotoxicity towards mammalian cells positively correlates with the magnitude of conformational changes of the unfolded form upon cell interaction

¹

,

²

,

³

et al. 2019

Self Cite

View full text Add to dashboard Cite

Porcine protegrin-1 (PG-1) is a broad-spectrum antimicrobial peptide (AMP) with potent antimicrobial activities. We produced recombinant PG-1 and evaluated its cytotoxicity toward various types of mammalian cell lines, including embryonic fibroblasts, retinal cells, embryonic kidney cells, neuroblastoma cells, alveolar macrophage cells, and neutrophils. The sensitivity of the different mammalian cells to cytotoxic damage induced by PG-1 differed significantly among the cell types, with retinal neuron cells and neutrophils being the most significantly affected. A circular dichroism analysis showed there was a precise correlation between conformational changes in PG-1 and the magnitude of cytotoxicity among the various cell type. Subsequently, a green fluorescent protein (GFP) penetration assay using positively charged GFPs indicated there was a close correlation between the degree of penetration of charged GFP into cells and the magnitude of PG-1 cytotoxicity. Furthermore, we also showed that inhibition of the synthesis of anionic sulphated proteoglycans on the cell surface decreases the cytotoxic damage induced by PG-1 treatment. Taken together, the observed cytotoxicity of PG-1 towards different membrane surfaces is highly driven by the membrane’s anionic properties. Our results reveal a possible mechanism underlying cell-type dependent differences in cytotoxicity of AMPs, such as PG-1, toward mammalian cells.

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2024 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.