Synthetic antimicrobial peptides Bac-5, BMAP-28, and Syn-1 can inhibit bovine respiratory disease pathogens in vitro
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ABSTRACT:
SUBMITTER: Cornejo S
PROVIDER: S-EPMC11345158 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundProtozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs) as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages.Methodology/principal findingsAn MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model.Conclusions/significanceInterestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials.
| S-EPMC3104953 | biostudies-literature
Project description:This study describes an attempt to replicate experiments from the paper "Effect of BMAP-28 Antimicrobial Peptides on Leishmania major Promastigote and Amastigote Growth: Role of Leishmanolysin in Parasite Survival," which was submitted to the Reproducibility Initiative for independent validation. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) and its isomers were previously shown to have potent antiparasitic activity against Leishmania major. We tested the effectiveness of L-BMAP-28 and two of its isomers, the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), in both unamidated and amidated forms, as anti-leishmanial agents against Leishmania major promastigotes in vitro. We observed that L-BMAP-28, as well as its D and RI isomers, demonstrate anti-leishmanial activity against L. major promastigotes in vitro. The inhibitory effect was lower than what was seen in the original study. At 2 µM of amidated peptides, the viability was 94%, 36%, and 66% with L-, D- and RI-peptides, versus 57%, 6%, and 18% in the original study.
| S-EPMC4269415 | biostudies-literature
Project description:BackgroundBovine leptospirosis is a widespread zoonotic disease, leading to serious economic losses in animal production and causing potential hazards to human health. Leptospiral lipopolysaccharide (L-LPS) plays an important role in leptospirosis pathogenicity.ObjectivesWith respect to L-LPS endotoxin-like activity, we examined bovine immune response to L-LPS and the inhibitory ability of bovine myeloid antimicrobial peptide-28 (BMAP-28) against L-LPS-induced immune activation in bovine cells.Materials and methodsIn this study, L-LPS-induced proinflammatory cytokine production in bovine cells was quantitatively measured with real-time PCR and ELISA, and we determined which cell membrane receptors (toll-like receptor [TLR]2 and TLR4) played a major role. In addition, the ability of BMAP-28 to inhibit L-LPS-induced endotoxin-like immune activation in bovine cells was determined by the decrease in cytokine secretion.ResultsL-LPS showed the ability to induce cytokine production in bovine cells, and its induction was TLR2-dependent. BMAP-28 was used to inhibit L-LPS-induced endotoxin-like activity. The function of BMAP-28 was to inhibit LPS-induced TLR2 expression and cytokine production.ConclusionsIn this study, the L-LPS immune response of bovine cells was significant, indicating that TLR2 is the predominant receptor for L-LPS. Due to L-LPS endotoxin-like activity, we found a strategy through using BMAP-28 to prevent L-LPS-induced TLR2-dependent immune activation in bovine cells.
| S-EPMC5013549 | biostudies-literature
Project description:Catheter-related infection makes up a large part of hospital infection and contributes 80% to all nosocomial urological infection, costing hundreds of millions dollar per year for treatment. Biodegradable hydrophilic material incorporating antibiotic substance is a promising way to prevent catheter-related infection. And antimicrobial peptide seems an optimal drug for its desirable antibiotic effect. In the current research, we produced a new kind of antibiotic material by incorporating antimicrobial peptide Bmap-28 with polyurethane PEGU25 and tested its effect on Proteus mirabilis in vitro. Compared with the control group, PEGU25 membrane incorporating Bmap-28 had a significant lower bacteria load after co-cultured with the Proteus mirabilis. And its antibiotic effect could be observed throughout the whole 7-day test. Also the Bmap-28 membrane could delay catheter obstruction caused by encrustation. Our findings reveal that PEGU25 incorporating Bmap-28 can well inhibit bacterial biofilm formation of common pathogens for catheter-related urinary tract infection in vitro, which makes it a promising antibiotic material for medical tubes for urology.
| S-EPMC4345405 | biostudies-other
Project description:Antimicrobial peptides (AMPs) exhibit multiple activities against bacteria and fungi. A bovine myeloid antimicrobial peptide (BMAP-28) belongs to the cathelicidin-derived AMPs and has antimicrobial activity. Due to the rapidly increasing number of infections and outbreaks caused by pan-drug-resistant Acinetobacter baumannii (PDRAB), we sought to determine whether BMAP-28 and its 4 analog peptides (A837, A838, A839, and A840) have antimicrobial activity against PDRAB. Furthermore, we clarified the possible mechanism of inhibition by which of BMAP-28 acts against PDRAB. In the current study, we examined the inhibitory effect of BMAP-28 and its 4 analog peptides on the growth of PDRAB through minimal inhibitory concentration (MIC) analysis and short time killing assays. We also evaluated the effects of BMAP-28 and its analogs on the bacterial cell surface through the use of field emission scanning electron microscopy (FE-SEM). In order to determine the inhibitory mechanism of BMAP-28, we examined the interaction between BMAP-28 and outer membrane proteins (OMPs), especially the interaction between BMAP-28 and A. baumannii OmpA (AbOmpA), which is the main component of OMPs, by using a quartz crystal microbalance (QCM). BMAP-28 and its 4 analogs were effective in inhibiting the growth of PDRAB and had rapid killing ability. BMAP-28 showed exceptionally strong and rapid inhibitory effects on PDRAB when compared to the other peptides and was also shown to cause damage to the cell surface of PDRAB. Moreover, QCM analysis provided evidence of potential interaction between BMAP-28 and AbOmpA. These data indicate that BMAP-28 is a promising candidate for the treatment of PDRAB infections and that its inhibitory effects were related with its binding to AbOmpA.
| S-EPMC6211872 | biostudies-literature
Project description:Mastitis, often caused by bacterial infection, is an inflammatory condition affecting the mammary glands. The condition is particularly prevalent in dairy cattle. Current treatment of bovine mastitis heavily relies on the use of antibiotics. To identify alternative solutions to antibiotic use, we evaluated the antimicrobial activity of 14 cathelicidins reported from 10 animal species. In conjunction, we assessed two bacteriocins against the bovine-mastitis causative bacterial panel, consisting of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis, Streptococcus agalactiae, Streptococcus dysgalactiae, and Streptococcus equi. Among the antimicrobial peptides (AMPs), cc-CATH3, ML-CATH, and PD-CATH proved to be highly active (minimum inhibitory concentration of 2-41 μg/mL, 0.2-10.3 μM) against all bacterial strains in the panel and field isolates from milk, with elevated somatic cell counts (≥ 500,000 cells/mL). Of the AMPs tested in this study, ML-CATH presented the highest level of effectiveness in controlling mastitis-associated bacterial strains while also possessing minimal cytotoxicity and functional stability against pH change and a high salt condition. The results of in silico analyses on the biochemical features of 12 helical cathelicidins revealed that the charge of AMPs appears to be a major determinant in killing Gram-negative bacteria. Furthermore, we observed a unique motif, "N(n≥3)-P(n≥1)-N(n≥3)", from the sequences of PMAP-36, cc-CATH3, ML-CATH, and PD-CATH that exhibits potent antimicrobial activity against a broad spectrum of bacteria compared to others. Our findings support the proposition that AMPs could serve as effective antimicrobial alternatives to conventional antibiotics in treating complex animal diseases caused by microbial infection, such as bovine mastitis.
| S-EPMC11566078 | biostudies-literature
Project description:We previously showed that bovine apolipoprotein A-II (apoA-II) had antimicrobial activity against Escherichia coli and the yeast Saccharomyces cerevisiae in PBS. We have characterized here the active domain of apoA-II using synthetic peptides. A peptide corresponding to C-terminal residues Leu(49)-Thr(76) exhibited significant antimicrobial activity against E. coli in PBS, but not against S. cerevisiae. Experiments using amino-acid-substituted peptides indicated that the residues Phe(52)-Phe(53)-Lys(54)-Lys(55) are required for the activity. Peptide Leu(49)-Thr(76) induced the release of calcein trapped inside the vesicles whose lipid composition resembles that of E. coli membrane, suggesting that peptide Leu(49)-Thr(76) can destabilize the E. coli membrane. CD measurements showed that the alpha-helicity of peptide Leu(49)-Thr(76) increased from 3.5 to 36% by addition of the vesicles. When E. coli cells were incubated with peptide Leu(49)-Thr(76), some proteins were released to the external medium, probably owing to membrane destabilization caused by the peptide. In electron micrographs of E. coli cells treated with peptide Leu(49)-Thr(76), transparent nucleoids and granulated cytoplasm were observed. Amino acid substitutions, Phe(52)Phe(53)-->AlaAla (Phe(52, 53)-->Ala) in peptide Leu(49)-Thr(76) caused the loss of antimicrobial activity against E. coli, although protein-releasing activity was retained. Electron micrographs of the cells treated with peptide Leu(49)-Thr(76)(Phe(52,53)-->Ala) revealed morphological change only at the nucleoids. Therefore peptide Leu(49)-Thr(76) appears to primarily target the cytoplasm rather than the membrane of E. coli cells.
| S-EPMC1220455 | biostudies-other
Project description:Antimicrobial peptides (AMPs) are biologically active molecules that can eradicate bacteria by destroying the bacterial membrane structure, causing the bacteria to rupture. However, little is known about the extent and effect of AMPs on filamentous fungi. In this study, we synthesized small molecular polypeptides by an inexpensive heat conjugation approach and examined their effects on the growth of Aspergillus flavus and its secondary metabolism. The antimicrobial agents significantly inhibited aflatoxin production, conidiation, and sclerotia formation in A. flavus. Furthermore, we found that the expression of aflatoxin structural genes was significantly inhibited, and the intracellular reactive oxygen species (ROS) level was reduced. Additionally, the antimicrobial agents can change membrane permeability. Overall, our results demonstrated that antimicrobial agents, safe to mammalian cells, have an obvious impact on aflatoxin production, which indicated that antimicrobial agents may be adopted as a new generation of potential agents for controlling aflatoxin contamination.
| S-EPMC8105457 | biostudies-literature
Project description:The antimicrobial resistance crisis is an ongoing major threat to public health safety. Low- and middle-income countries are particularly susceptible to higher fatality rates and the economic impact of antimicrobial resistance (AMR). As an increasing number of pathogens emerge with multi- and pan-drug resistance to last-resort antibiotics, there is an urgent need to provide alternative antibacterial options to mitigate disease transmission, morbidity, and mortality. As identified by the World Health Organization (WHO), critically important pathogens such as Klebsiella and Pseudomonas species are becoming resistant to last-resort antibiotics including colistin while being frequently isolated from clinical cases of infection. Antimicrobial peptides are potent amino acid sequences produced by many life forms from prokaryotic, fungal, plant, to animal species. These peptides have many advantages, including their multi-hit mode of action, potency, and rapid onset of action with low levels of resistance being evident. These innate defense mechanisms also have an immune-stimulating action among other activities in vivo, thus making them ideal therapeutic options. Large-scale production and formulation issues (pharmacokinetics, pharmacodynamics), high cost, and protease instability hinder their mass production and limit their clinical application. This review outlines the potential of these peptides to act as therapeutic agents in the treatment of multidrug-resistant infections considering the mode of action, resistance, and formulation aspects. Clinically relevant Gram-positive and Gram-negative pathogens are highlighted according to the WHO priority pathogen list.
| S-EPMC10454446 | biostudies-literature
Project description:In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular hydrogen bonds, and the overall hydrophobicity by modifications to the central ring and the side chains. This approach allowed us to better understand the influence of these features on the antimicrobial activity and selectivity. We found that the overall hydrophobicity had a more significant impact on antimicrobial and hemolytic activity than the conformational stiffness. A novel compound was discovered which has MICs of 0.78 μg/mL against S. Aureus and 6.25 μg/mL against E. Coli, similar to the well-known antimicrobial peptide, MSI-78.
| S-EPMC3072574 | biostudies-literature