Antimicrobial peptides act on the rumen the performance of castrated bulls

Background Many countries have already banned the use of antibiotics in animal husbandry,making it extremely difficult to maintain animal health in livestock breeding.In the livestock industry,there is an urgent need to develop alternatives to antibiotics which will not lead to drug resistance on prolonged use.In this study,eighteen castrated bulls were randomly divided into two groups.The control group(CK)was fed the basal diet,while the antimicrobial peptide group(AP)was fed the basal diet supplemented with 8 g of antimicrobial peptides in the basal diet for the experimental period of 270 d.They were then slaughtered to measure production performance,and the ruminal contents were isolated for metagenomic and metabolome sequencing analysis.Result The results showed that antimicrobial peptides could improve the daily weight,carcass weight,and net meat weight of the experimental animals.Additionally,the rumen papillae diameter and the micropapillary density in the AP were significantly greater than those in the CK.Furthermore,the determination of digestive enzymes and fermentation parameters showed that the contents of protease,xylanase,andβ-glucoside in the AP were greater than those in the CK.However,lipase content in the CK was greater than that in the AP.Moreover,the content of acetate,propionate,butyrate,and valerate was found to be greater in AP than those in CK.The metagenomic analysis annotated 1993 differential microorganisms at the species level.The KEGG enrichment of these microorganisms revealed that the enrichment of drug resistance-related pathways was dramatically decreased in the AP,whereas the enrichment of immune-related pathways was significantly increased.There was also a significant reduction in the types of viruses in the AP.187 probiotics with significant differences were found,135 of which were higher in AP than in CK.It was also found that the antimicrobial mechanism of the antimicrobial peptides was quite specific.Seven low-abundance microorganisms(Acinetobactersp.Ac1271,Aequorivita soesokkakensis,Bacillus lacisalsi,Haloferax larsenii,Lysinibacillussp.3DF0063,Parabacteroidessp.217,Streptomycessp.So13.3)were found to regulate growth performance of the bull negatively.Metabolome analysis identified 45 differentially differential metabolites that significantly different between the CK and the AP groups.Seven upregulated metabolites(4-pyridoxic acid,Ala-Phe,3-ureidopropionate,hippuric acid,terephthalic acid,L-alanine,uridine 5-monophosphate)improve the growth performance of the experimental animals.To detect the interactions between the rumen microbiome and metabolism,we associated the rumen microbiome with the metabolome and found that negative regulation between the above 7 microorganisms and 7 metabolites.Conclusions This study shows that antimicrobial peptides can improve the growth performance of animals while resisting viruses and harmful bacteria and are expected to become healthy alternatives to antibiotics.We demonstrated a new antimicrobial peptides pharmacological model.We demonstrated low-abundance microorganisms may play a role by regulating the content of metabolites.

Design methods for antimicrobial peptides with improved performance

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more difficult.In this regard,developing new antimicrobial agents to combat antibiotic-resistant strains has become a top priority.Antimicrobial peptides(AMPs),a ubiquitous class of naturally occurring compounds with broadspectrum antipathogenic activity,hold significant promise as an effective solution to the current antimicrobial resistance(AMR)crisis.Several AMPs have been identified and evaluated for their therapeutic application,with many already in the drug development pipeline.Their distinct properties,such as high target specificity,potency,and ability to bypass microbial resistance mechanisms,make AMPs a promising alternative to traditional antibiotics.Nonetheless,several challenges,such as high toxicity,lability to proteolytic degradation,low stability,poor pharmacokinetics,and high production costs,continue to hamper their clinical applicability.Therefore,recent research has focused on optimizing the properties of AMPs to improve their performance.By understanding the physicochemical properties of AMPs that correspond to their activity,such as amphipathicity,hydrophobicity,structural conformation,amino acid distribution,and composition,researchers can design AMPs with desired and improved performance.In this review,we highlight some of the key strategies used to optimize the performance of AMPs,including rational design and de novo synthesis.We also discuss the growing role of predictive computational tools,utilizing artificial intelligence and machine learning,in the design and synthesis of highly efficacious lead drug candidates.

Differential expression of antimicrobial peptides in human fungal keratitis

AIM:To analyze a series of antimicrobial peptides(AMPs)in corneal tissue from individuals with fungal keratitis(FK)during the active phase of the fungus infection and after healing.METHODS:Patients undergone lamellar keratoplasty for the treatment of severe FK or corneal scar had their corneal buttons sampled.Quantitative real-time polymerase chain reaction(PCR)was used to ascertain the gene expression of human beta-defensin(HBD)-1,-2,-3,-9,S100A7,8,9,and LL-37.RESULTS:All AMPs’messenger ribonucleic acid(mRNA)expression was considerably elevated in all samples(n=12).In contrast to controls,where HBD-2,-3,and S100A7 mRNAs were expressed at very low levels,it was discovered that HBD-1,-9,S100A8,S100A9,and LL-37 were constitutively expressed in all healed samples(n=4).HBD-1,-2-3,S100A7,and LL-37 mRNAs were significantly increased in all active FK samples(n=8).The levels of HBD-9,S100A8,and S100A9 mRNAs were moderately upregulated in all active FK samples.Subgroup comparison showed that HBD-2 was significantly increased in Fusarium keratitis samples(n=5),and LL-37 mRNAs were significantly enhanced in Aspergillus keratitis samples(n=3).Whereas there was not significantly increased of HBD-1,-3,-9,S100A7,8,9 mRNA in Aspergillus keratitis samples compared with Fusarium keratitis samples.CONCLUSION:AMPs expression is increased in active FK,but not all AMPs are equally expressed.HBD-2 and LL-37 expression levels are the highest,showing some specificity of AMP expression related to FK.Human AMPs,particularly HBD-2 may play a significant role in Fusarium keratitis and LL-37 might be the key player in Aspergillus keratitis.

Effects of Antimicrobial Peptides on Production,Slaughter Performance and Blood Routine of Tan Sheep

[Objectives]This study was conducted to analyze effects of antimicrobial peptides added to the diet of Tan sheep on their production, slaughter performance and blood composition. [Methods] Ninety two four-month-old Tan sheep were randomly divided into two treatment groups according to their body weight, 46 in each group. The control check group(CK) was feed with conventional diet, and the experimental group was fed with the addition of antimicrobial peptide on the basis of the conventional diet, with the added amount of 2.5 g/sheep per day. The experimental period was 60 d. [Results] The incidence rate was 75.06% lower in the experimental group than in the CK. The average daily weight gain per sheep was 11.27% higher in the experimental group than in the CK(P<0.05). The feed conversion ratio was 8.45% lower in the experimental group than in the CK(P<0.05). The average daily gross profit per sheep was 12.12% higher in the experimental group than in the CK. For slaughter performance, the data difference of each item was not significant. The PH at 45 min and 24 h after slaughter was within the normal range of fresh mutton. The cooked meat percentage and water loss rate showed no significant differences(P>0.05). The marbling ranged from 2.45 to 2.50, indicating that the fat content was moderate, and the difference between groups was not significant(P>0.05). The flesh color ranged from 3.00 to 3.15, between light red and bright red, belonging to the normal color of mutton, and the difference between groups was not significant(P>0.05). The shear force was between 2.50 and 2.65, without a significant difference between groups(P>0.05). The white blood cells, lymphocytes and platelets in the experimental group were lower than those in the CK(P<0.01). The erythrocytes and hemoglobin in the erythrocyte group were higher than those in the CK(P<0.05). The neutrophils and monocytes in the experimental group were lower than those in the CK(P<0.05). [Conclusions] This study provides a technical basis for the rational use of antimicrobial peptides and their application in ruminants.

Analysis of the Antimicrobial Activity of Antimicrobial Peptides Extracted from Immunized Tenebrio molitor Induced by Different Microbial Treatments Against 26 Pathogens

[Objective] The study was to explore whether antimicrobial activity of the antimicrobial peptides extracted from immunized Tenebrio molitor varied with different pathogens as inducers.[Method]By inducing T.molitor hungry larvaes to generate immune response via feeding with bacteria and with fungi or actinomycete post to pricking,the antimicrobial peptides extracts were obtained by grinding and centrifuging the cultures.Its antimicrobial activity against 26 pathogens was measured by bacteriostatic ring,and evaluated by trisection to four types and inhibitory spectrum.[Result]Both the antimicrobial activity and antimicrobial spectrum of the antimicrobial peptides extracts varied remarkably among different pathogens as inducers.[Conclusion]Bio-control used strains have obvious advantage in inducing the insect to express body fluid immunity material-antimicrobial peptides.

The application of antimicrobial peptides as growth and health promoters for swine

With the widespread ban on the use of antibiotics in swine feed, alternative measures need to be sought to maintain swine health and performance, Antimicrobial peptides （AMPs） are part of the nonspecific defense system and are natural antibiotics produced by plants, insects, mammalians, and micro-organisms as well as by chemical synthesis. Due to their broad microbicidal activity against various fungi, bacteria and enveloped viruses AMPs are a potential alternative to conventional antibiotics for use in swine production. This review focuses on the structure and mechanism of action of AMPs, as well as their effects on performance, immune function and intestinal health in pigs. The aim is to provide support for the application of AMPs as feed additives replacing antibiotics in swine nutrition.

Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Antimicrobial peptides(AMP)are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells,Paneth cells,as well as immune cells in the gastrointestinal(GI)tract.They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections.Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease(IBD)and converge on the function of AMP,the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years.In this frontier article,we discuss the function and mechanisms of AMP in the GI tract,examine the interaction of AMP with the gut microbiome,explore the role of AMP in the pathogenesis of IBD,and review translational applications of AMP in patients with IBD.

Antimicrobial peptides: mechanism of action, activity and clinical potential

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides

Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.

Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish

Antimicrobial peptides （AMPs）, as key immune effectors, play important roles in the innate immune system of invertebrates. Different types of AMPs, including Penaeidin, Crustin, ALF （anti- lipopolysaccharide factor） have been identified in different penaeid shrimp; however, systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited. In this study, we analyzed the expression profiles of AMPs in the Chinese shrimps, Fenneropenaeus chinensis, simultaneously by real-time RT-PCR （reverse transcription-polymerase chain reaction） when shrimp were challenged with Micrococcus lysodeikticus （Gram-positive, G＋） or Hbrio anguillarium （Gram-negative, G-）. Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium, and one AMP also showed different expression profiles when shrimp were challenged with different bacteria. Furthermore, the expression of these AMPs showed temporal expression profiles, suggesting that different AMPs function coordinately in bacteria-infected shrimp. An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AMPs. The current study showed that Relish could regulate the transcription of different AMPs in shrimp. Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp. These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

Mechanisms of antimicrobial peptides as characterized by solid-state NMR

Antimicrobial peptides(AMP)are small proteins that play critical roles in host defense against microbe invasion.Many AMPs disrupt the cellular membrane of microbe,while the mechanism of action of AMPs can be very sophisticated.Solid-state NMR(SSNMR)technique is powerful in characterizing the mechanism of AMPs in vivo and in vitro.This review summarizes the recent advance of SSNMR technique in AMP mechanisms characterization.We highlight the sample preparation approaches,the SSNMR spectroscopic methods,and a number of outstanding examples of AMP mechanisms elucidated via SSNMR spectroscopy.

Research progress of plant antimicrobial peptides

Plant antimicrobial peptides are a very large family of antimicrobial peptides,which have strong resistance to various pathogenic microorganisms,especially fungi.With the increasing use of antibiotics,the problems caused by antibiotics,including antibiotic residues and pathogen resistance,are becoming more and more prominent.The research on antimicrobial peptides as new antibiotic substitutes is also a hot spot.This article introduces the action sites and antibacterial mechanisms of several plant antimicrobial peptides,as well as the application of plant antimicrobial peptides in the fields of medicine,agriculture,and food preservation.

Identication of Antimicrobial Peptides Using Chou’s 5 Step Rul

With the advancement in cellular biology,the use of antimicrobial peptides(AMPs)against many drug-resistant pathogens has increased.AMPs have a broad range of activity and can work as antibacterial,antifungal,antiviral,and sometimes even as anticancer peptides.The traditional methods of distinguishing AMPs from non-AMPs are based only on wet-lab experiments.Such experiments are both time-consuming and expensive.With the recent development in bioinformatics more and more researchers are contributing their effort to apply computational models to such problems.This study proposes a prediction algorithm for classifying AMPs and distinguishing between AMPs and non-AMPs.The proposed methodology uses machine learning algorithms to predict such sequences.A dataset was formulated based on 1902 samples of AMPs and 3997 samples of non-AMPs.Machine learning algorithms are trained on a xed number of succinct coefcients retaining sequence and composition information of primary structures.The features are extracted using position relative incidence and statistical moments.System performance is validated via various validation tests including a 10-fold cross-validation approach.An overall accuracy of 95.43%was achieved.A comparison of results with existing methodologies shows that the proposed methodology outperformed existing methodologies in terms of prediction accuracy.

NMR assisted studies on the solution structures and functions of antimicrobial peptides Dedicated to Professor Chaohui Ye on the occasion of his 80th birthday

Microbial resistance has now become a global public health concern,and the spread of multidrug-resistant bacteria also threatens human health.Antimicrobial peptides(AMPs)are a class of small peptides with antibacterial,anti-inflammatory,anti-infective,antioxidation,anti-tumor,antiviral functions and immune regulation activities.Due to the small sizes,their structures are easily studied by nuclear magnetic resonance(NMR)techniques.Compared to traditional antibiotics,AMPs have specific antibacterial mechanisms,and do not easily result in the production of drug-resistant strains.Thus,the development of new antimicrobial peptides and their wide use instead of chemical antibiotics are of great significance to human health.In this review,we first summarized the relationship between the structures and functions of antimicrobial peptides.Then,we focused on examples,cathelicidins,a group of cationic antimicrobial peptides with multiple biological activities.Especially,cathelicidin BF30 or BF34,composed of 30 or 34 amino acids,were from the venom glands of the Bungarus fasciatus snake and were considered to be the most active antibacterial peptides among different cathelicidin members.Their solution structures determined by NMR are a-helixes,which are useful in designing new and stable peptides with similar framework,including stapple peptides by inducing chemical modifications in the sidechains of some residues,as well as cyclic peptides by inducing disulfide bond between cysteines in the sequences.

Effect of Antimicrobial Peptides and Chemicals Produced by Animals on <i>Aspergillus fumigatus</i>

The problem of multidrug-resistant pathogens as bacteria, fungi and yeast in addition to the restriction of using antibiotics as growth promoting substances in food has attracted the attention to looking for alternative sources instead of conventional antibiotics like natural products which have antimicrobial activity. Much interests and researches have been focused on using natural antimicrobial peptides and chemicals extracted from animal secretions and some insect’s venoms as they exhibit antimicrobial activity against pathogens with lower resistance and higher synergistic effects if they were given in combination with blends of them. In this paper, some antimicrobial chemicals extracted from giraffes are shown in addition to their activity against Aspergillus fumigatus species using optical density analysis technique then their Minimum Inhibitory Concentrations (MIC) will be determined as well as ICs 50 to measure the potency to inhibit a biological function using programmes like Gene5, graph pad prism as well as testing antimicrobial activity of some chemicals which are provided in animal secretions.

Antimicrobial Peptides from the Plants

AMPs （antimicrobial peptides） are small, mostly basic peptides that range in size from 2-9 kDa, and they are an important component of the innate defense system of plants where they are effector molecules considered to be an important defense barrier to pathogens and pests. Nine families of antimicrobial peptides have been identified in plants, including thionins, defensins, lipid transfer proteins, hevein and knotting-like peptides, four cysteine-types, and the recently reported shepherdins, snakins and cyclotides. They are part of both permanent and inducible defense barriers of plants. Transgenic overexpression of the corresponding genes leads to enhanced tolerance to pathogens, and peptide-sensitive pathogen mutants have reduced virulence. In this review, the recent studies on peptides from plant sources, including peptides isolated from indigenous medicine and edible plants of Central-Asia, are briefly discussed with a focus on their origins, antioxidant, antitumor activities and the possible mechanisms of actions in order to provide a profile of important plant peptides.

Effect of Antimicrobial Peptides and Chemicals Produced by Animals on Liver Microsomal Enzymes CYP450

The problem of multidrug-resistant pathogens as bacteria, fungi and yeast in addition to the restriction of using antibiotics as growth promoting substances in feed has attracted attention for looking for alternative sources instead of conventional antibiotics like natural products which have antimicrobial activity. Much interest and researches have been focused on using natural antimicrobial peptides and chemicals extracted from animal secretions and some insect’s venoms as they exhibit antimicrobial activity against pathogens with lower resistance and higher synergistic effects if they were given in combination with blends of them. In this paper, some antibacterial peptides extracted from honeybees venom and expression with yeast Saccharomyces cerevisiae will be discussed as well as antimicrobial chemicals extracted from giraffes in addition to their inhibitory effects on liver microsomal enzymes CYP450 will be discussed also with its activity against microorganisms which are Agrobacterium rhizogenes, Aspergillus niger, Candida albicans and E. coli using optical density analysis technique then their minimum inhibitory concentrations (MIC) will be determined as well as ICs 50 to measure the potency to inhibit a biological function using programmes like Gene5, graph pad prism and clone manager as well as testing antimicrobial activity of some chemicals which are provided in animal secretions.

To resolve recent natural immune defense effects of antimicrobial peptides in the gastrointestinal tract

The human gut is the normal habitat of a lot of microorganisms; in the long process of evolution they have developed a symbiotic relationship with the host. Under normal circumstances they do not damage the health, which totally owes to the barrier functions of the integral intestinal mucosa. Intestinal lnucosal barriers are mainly composed of four parts： mechanical barrier, immune barrier, chemical and biological barrier. Each of these functions has corresponding structural basis, an important barrier to prevent harmful substances and pathogens in the gut into the inner environment of the body, and to maintain a stable internal environment.

Effect of disulfide bridges deletion on the conformation of the androctonin,polyphemusin-I,and thanatin antimicrobial peptides:molecular dynamics simulation studies

In this work, the role of the disulfide bridges in the maintenance of the secondary structure of the antimicrobial peptides androctonin, poly-phemusin-I, and thanatin is analyzed on the basis of their structural characteristics and of three of their respective mutants, andry4, poly4, and thany2, in which all the cysteine residues have been replaced with tyrosine residues. The absence of the disulfide bridges in andry4, poly4, and thany2 seems to be compensated by an overall enforcement of the original hydrogen bonds and by extra attractive interactions between the aromatic rings of the tyrosine residues. In spite of the mutations, the original β-hairpin structures are maintained in the three mutants, but the best conformational similarities are found for the androctonin/andry4 pair.

Advances in Antimicrobial Peptides and Expression Strategy

Antimicrobial peptides are widely distributed in nature,existing in organisms of plants,insects,and vertebrates.It has been approved that antimicrobial peptides have broad spectrum antimicrobial activities,and play a key modulatory role in the innate immune response and tumor inhibiting activity.Due to the special action mechanism,the antimicrobial peptides become a hot field of genetic engineering.In the present paper,the general properties,mechanism of action,application value,existing problems,the latest progress and the expression strategy were discussed.