Dataset Information

In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5.

ABSTRACT: Antimicrobial peptides (AMP), part of the innate immune system, are well studied for their ability to kill pathogenic microorganisms. However, many also possess important immunomodulatory effects, and this area has potential for the development of novel therapies to supplement traditional methods such as the use of antibiotics. Here, we characterise the microbicidal and immunomodulatory potential of the proline-rich bovine AMP, Bactenecin 5 (Bac5). We demonstrate broad antimicrobial activity, including against some mycobacterial species, which are important pathogens of fish, cattle and humans. Bac5 is able to activate macrophage-like THP-1 cells and can synergistically trigger the upregulation of tnf-? when co-stimulated with M. marinum. Furthermore, Bac5 sensitises A549 epithelial cells to stimulation with TNF-?. For the first time, we characterise the activity of Bac5 in vivo, and show it to be a potent chemokine for macrophages in the zebrafish (Danio rerio) embryo model of infection. Bac5 also supports the early recruitment of neutrophils in the presence of M. marinum. In the absence of host adaptive immunity, exogenous injected Bac5 is able to slow, although not prevent, infection of zebrafish with M. marinum.

SUBMITTER: Price RL

PROVIDER: S-EPMC6326515 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5.

Price R L RL Bugeon L L Mostowy S S Makendi C C Wren B W BW Williams H D HD Willcocks S J SJ

PloS one 20190109 1

Antimicrobial peptides (AMP), part of the innate immune system, are well studied for their ability to kill pathogenic microorganisms. However, many also possess important immunomodulatory effects, and this area has potential for the development of novel therapies to supplement traditional methods such as the use of antibiotics. Here, we characterise the microbicidal and immunomodulatory potential of the proline-rich bovine AMP, Bactenecin 5 (Bac5). We demonstrate broad antimicrobial activity, in ...[more]

PMID: 30625198

Similar Datasets

Project description:Antimicrobial peptides (AMPs) have recently attracted attention as promising antibacterial agents capable of acting against resistant bacterial strains. In this work, an approach was applied, consisting of the conjugation of a peptide related to the sequences of bactenecin 7 (Bac7) and oncocin (Onc112) with the alkyl(triphenyl)phosphonium (alkyl-TPP) fragment in order to improve the properties of the AMP and introduce new ones, expand the spectrum of antimicrobial activity, and reduce the inhibitory effect on the eukaryotic translation process. Triphenylphosphonium (TPP) derivatives of a decapeptide RRIRPRPPYL were synthesized. It was comprehensively studied how the modification of the AMP affected the properties of the new compounds. It was shown that while the reduction in the Bac7 length to 10 a.a. residues dramatically decreased the affinity to bacterial ribosomes, the modification of the peptide with alkyl-TPP moieties led to an increase in the affinity. New analogs with structures that combined a decapeptide related to Bac7 and Onc112-Bac(1-10, R/Y)-and TPP attached to the C-terminal amino acid residue via alkylamide linkers, inhibited translation in vitro and were found to be more selective inhibitors of bacterial translation compared with eukaryotic translation than Onc112 and Bac7. The TPP analogs of the decapeptide related to Bac7 and Onc112 suppressed the growth of both Gram-negative bacteria, similar to Onc112 and Bac7, and Gram-positive ones, similar to alkyl-TPP derivatives, and also acted against some resistant laboratory strains. Bac(1-10, R/Y)-C2-TPP, containing a short alkylamide linker between the decapeptide and TPP, was transferred into the E. coli cells via the SbmA transporter protein. TPP derivatives of the decapeptide Bac(1-10, R/Y) containing either a decylamide or ethylamide linker caused B. subtilis membrane depolarization, similar to alkyl-TPP. The Bac(1-10, R/Y)-C2-TPP analog was proven to be non-toxic for mammalian cells using the MTT test.

Project description:BackgroundThe endometrium is commonly infected with bacteria leading to severe disease of the uterus in cattle and humans. The endometrial epithelium is the first line of defence for this mucosal surface against bacteria and Toll-like receptors (TLRs) are a critical component of the innate immune system for detection of pathogen associated molecular patterns (PAMPs). Antimicrobial peptides, acute phase proteins and Mucin-1 (MUC-1) also provide non-specific defences against microbes on mucosal surfaces. The present study examined the expression of innate immune defences in the bovine endometrium and tested the hypothesis that endometrial epithelial cells express functional receptors of the TLR family and the non-specific effector molecules for defence against bacteria.MethodsBovine endometrial tissue and purified populations of primary epithelial and stromal cells were examined using RT-PCR for gene expression of TLRs, antimicrobial peptides and MUC-1. Functional responses were tested by evaluating the secretion of prostaglandin E(2) and acute phase proteins when cells were treated with bacterial PAMPs such as bacterial lipopolysaccharide (LPS) and lipoproteins.ResultsThe endometrium expressed TLRs 1 to 10, whilst purified populations of epithelial cells expressed TLRs 1 to 7 and 9, and stromal cells expressed TLRs 1 to 4, 6, 7, 9 and 10. The TLRs appear to be functional as epithelial cells secreted prostaglandin E(2) in response to bacterial PAMPs. In addition, the epithelial cells expressed antimicrobial peptides, such as Tracheal and Lingual Antimicrobial Peptides (TAP and LAP) and MUC-1, which were upregulated when the cells were treated with LPS. However, the epithelial cells did not express appreciable amounts of the acute phase proteins haptoglobin or serum amyloid A.ConclusionEpithelial cells have an essential role in the orchestration of innate immune defence of the bovine endometrium and are likely to be the key to prevention of endometrial infection with bacteria.

Dataset Information

In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5.

Publications

In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets