Defense Peptides Research Articles

Antibacterial Activity and Action Mechanism of Synthetic Interleukin-8 Derived Peptides Against Flavobacterium psychrophilum.

In Chile, Atlantic salmon and rainbow trout face significant production challenges due to the presence of Flavobacterium psychrophilum, which generates severe disease issues and economic losses. To address this, the salmon industry relies on vaccines and antibiotics, the latter raising concerns about bacterial resistance. For that reason, our study explores an alternative strategy for controlling F. psychrophilum infections based on host defence peptides. We previously identified and characterised IL-8-derived salmonid peptides (ssIL-8α and omIL-8α) with potential antimicrobial properties. In the current study, we further investigated the antibacterial activity and mechanism of action of these peptides against F. psychrophilum. First, we demonstrated the antibacterial activity of ssIL-8α and omIL-8α synthetic peptides. Then we evaluated the effects of these peptides on membrane fluidity and localisation on bacterial cells by fluorescence microscopy as well as its impact on bacterial morphology and ultrastructure by electron microscopy. The results indicate that the ssIL-8α at 30 μM exhibits superior efficacy in inhibiting the growth of F. psychrophilum. Also, both ssIL-8α and omIL-8α can bind to pathogen membrane, but ssIL-8α exhibits a higher binding capacity compared to omIL-8α against F. psychrophilum. omIL-8α exhibited the ability to induce early membrane alterations within 15 min, at concentrations of 15 or 30 μM. The SEM and TEM micrographs showed membrane disruption of the bacteria after incubation with ssIL-8α or omIL-8α. However, the damage was more pronounced in the ssIL-8α treatment, as evidenced by a complete detachment of the outer membrane after a 20-min exposure of F. psychrophilum. This study reveals that these peptides significantly alter bacterial membrane morphology, leading to bacterial death, highlighting their potential as alternative treatments in flavobacterial disease control. This work contributes to understanding host defence peptides' role in combating bacterial infections and reducing antibiotic resistance in aquaculture.

Effects of Cigarette Smoking on Host Defense Peptides in Saliva of Patients with Periodontitis

Background: Smoking cigarettes is linked to a number of diseases (systemic and oral), and affect both innate and adaptive immunity. Host defense peptides, often known as antimicrobial peptides (AMPs), are a component of the innate immune system and regarded as a group of chemically active oligopeptides that are poisonous to harmful microbes. Aims: The goal of this research was to shed light on the effect of cigarette smoking on the production of host defense peptides in periodontitis patients. Methods and Materials: Eighty-five participants were included in this study. Periodontal health assessed by: PLI, GI, BOP, PPD and CAL. Saliva samples were collected from all subjects. ELISA was carried out to estimate the levels of beta defensin and cathelicidin. Statistical analysis was performed using SPSS version 24. The ANOVA parametric test was used to determine and detect the differences between independent study groups, and the Tukey honestly significant difference (HSD)/post hoc test was performed to determine if there is any statistical connection between two data sets (intergroup comparison). Results: The study findings showed both smokers and non smokers with periodontitis had considerably greater levels of beta defensin and cathelicidin than healthy controls. There was statistically significant reduction in beta defensin between smokers and non smokers (p<0.001); whereas no significant differences found between smokers and non smokers regarding cathelicidin level. Conclusions: These findings suggested that, in the context of periodontal diseases, smoking can affect the protein levels of beta defensin but not the levels of cathelicidin

Cloning and Functional Analysis of Skin Host Defense Peptides from Yakushima Tago’s Brown Frog (Rana tagoi yakushimensis) and Development of Serum Endotoxin Detection System

Background/Objective: Amphibian skin is a valuable source of host defense peptides (HDPs). This study aimed to identify HDPs with novel amino acid sequences from the skin of Rana tagoi yakushimensis and analyze their functions. Methods: cDNAs encoding HDP precursors were cloned and sequenced using RT-PCR and 3′-RACE. The novel HDPs were synthesized to evaluate their antimicrobial activity, antioxidant activity, and cytotoxicity. Antimicrobial activity was evaluated by way of broth microdilution and endotoxin- and β-glucan-binding capacity using an enzyme-linked endotoxin binding assay (ELEBA) and a modified ELEBA, respectively. Results: Nine cDNAs encoding precursors for various HDP families, including temporin, ranatuerin-2, brevinin-1, amurin-9, and a novel yakushimin peptide, were identified. Brevinin-1TYa exhibited antibacterial activity against Staphylococcus aureus, and brevinin-1TYa and amurin-9TYa induced morphological changes in Escherichia coli and S. aureus. Yakushimin-TYa, amurin-9TYa, and brevinin-1TYa showed concentration-dependent antibacterial effects against the plant pathogens Xanthomonas oryzae pv. oryzae and Clavibacter michiganensis subsp. michiganensis. Amurin-9TYa demonstrated strong binding affinity to lipopolysaccharide, lipoteichoic acid, and β-glucan, exhibited antioxidant activity, and lacked cytotoxicity, making it a promising therapeutic candidate. Moreover, brevinin-1TYa showed strong cytotoxicity, whereas yakushimin-TYa exhibited weak cytotoxicity. Conclusions: These findings highlight the potential of these peptides, particularly amurin-9TYa, for future applications as antimicrobial and therapeutic agents.

Novel Peptide-Drug Conjugates with Dual Anticancer Activity.

Cationic antimicrobial peptides (AMPs), also called host defence peptides, have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but it remains relatively less explored in the generation of anticancer candidates. In this study, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, were conjugated to L-K6, a lysine/leucine-rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from reduction in the activity of the parent drugs to their conservation or even enhancement. Notably, the conjugates retained some anti-TDP1 activity and displayed intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.

Discovery of Novel Thanatin-like Antimicrobial Peptides from Bean Bug Riptortus pedestris.

Background: Endogenous antimicrobial peptides (AMPs) are evolutionarily ancient molecular factors of innate immunity that play a key role in host defense. The study of the diversity of animal defense peptides has important applications in the context of the growing global antimicrobial resistance. Methods: In this study using a transcriptome mining approach, we found three novel thanatin-like β-hairpin AMPs in the bean bug Riptortus pedestris, named Rip-2, Rip-3, and Rip-4. The peptides were expressed in the bacterial system, and their antimicrobial activities were evaluated both in vitro and in vivo. Results: Homologs of the discovered AMPs are widely distributed among different members of the infraorder Pentatomomorpha. Rip-2 was shown to have the most similar structure and LptA-targeting mechanism of action to those of thanatin, but the former peptides demonstrated a higher activity against key Gram-negative ESKAPE pathogens and also displayed a significant efficacy in a lethal model of septicemia caused by E. coli in mice at daily doses greater than 5 mg/kg. In contrast, Rip-3 and Rip-4 peptides caused bacterial membrane damage, did not induce bacterial resistance, and exhibited a strong selectivity against Bacillus and Mycobacterium spp. Conclusions: This study extends the knowledge of the structure and functions of insect host defense AMPs. Each of the novel β-hairpin peptides has a potential to be a template for the development of selective antibiotic drugs.

Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis

Interleukin (IL)–33 is a key responder to intestinal injury and inflammation. In the colon, it is expressed by several cell populations, with the specific cellular source likely determining its role. The colonic epithelium expresses IL-33; however, the factors controlling its production and the specific epithelial lineage(s) expressing IL-33 are poorly understood. We recently reported that colonic epithelial IL-33 is induced by inhibition of glycogen synthase kinase-3β (GSK3β), but the signaling pathway mediating this induction is unknown. Here we tested the role of Wnt/β-catenin signaling in regulating colonic epithelial IL-33 at homeostasis and in injury-induced colitis. Transcriptomic analysis shows that epithelial IL-33 localizes to stem and progenitor cells. Ligand activation of Wnt/β-catenin signaling induced IL-33 in colonic organoid and cell cultures. Furthermore, small-molecule disruption of β-catenin interaction with cyclic AMP response element binding protein (CBP) prevented epithelial IL-33 induction. Antagonism of CBP/β-catenin signaling also prevented rapid epithelial IL-33 induction in dextran sodium sulfate (DSS)-mediated colitis, and was associated with maintenance of crypt-expressed host defense peptides. Together, these findings show β-catenin-driven production of epithelial IL-33 is an early response to colonic injury that shapes the crypt base defense response and suggest an immunoregulatory role for the stem cell niche in tissue injury.

Biochemistry, Mechanistic Intricacies, and Therapeutic Potential of Antimicrobial Peptides: An Alternative to Traditional Antibiotics.

The emergence of drug-resistant strains of pathogens becomes a major obstacle to treating human diseases. Antibiotics and antivirals are in the application for a long time but now these drugs are not much effective anymore against disease-causing drugresistant microbes and gradually it is becoming a serious complication worldwide. The development of new antibiotics cannot be a stable solution to treat drug-resistant strains due to their evolving nature and escaping antibiotics. At this stage, antimicrobial peptides (AMPs) may provide us with novel therapeutic leads against drug-resistant pathogens. Structurally, antimicrobial peptides are mostly α-helical peptide molecules with amphiphilic properties that carry the positive charge (cationic) and belong to host defense peptides. These positively charged AMPs can interact with negatively charged bacterial cell membranes and may cause the alteration in electrochemical potential on bacterial cell membranes and consequently lead to the death of microbial cells. In the present study, we will elaborate on the implication of AMPs in the treatment of various diseases along with their specific structural and functional properties. This review will provide information which assists in the development of new synthetic peptide analogues to natural AMPs. These analogues will eliminate the limitations of natural AMPs like toxicity and severe hemolytic activities.

Investigation on the in vitro effects of resveratrol on peripheral blood mononuclear cells harvested from healthy and atopic dogs

Canine atopic dermatitis (AD) is a common skin disease. Many therapeutic options are available to decrease inflammation and ameliorate pruritus. However, those treatments are associated with side effects, a long lag phase for efficacy, or high expense. Natural plant extracts have been identified as possible, safer alternatives to traditional anti-inflammatory and antipruritic drugs. Resveratrol has been revisited as a new, possible alternative for its numerous beneficial properties. The purpose of this study was to evaluate the in vitro effects of resveratrol on peripheral blood mononuclear cells (PBMC) harvested from healthy and atopic privately-owned dogs.The PBMC harvested from nine healthy and 11 atopic dogs were isolated and exposed to four concentrations (1.5-9 μg/mL) of resveratrol both with or without phytohemagglutinin stimulation. After 24 h cytotoxicity, host defense peptides (HDPs), as well as oxidative stress (catalase and superoxide dismutase), and pro-inflammatory cytokines were assessed. Cytotoxicity was not observed in either group under any experimental conditions. An increase in catalase was only seen in healthy PBMC after exposure to low concentrations of resveratrol (p ≤ 0.03). Resveratrol did not show any effect on canine HDPs. Compared to baseline, there was a significant reduction in monocyte chemotactic protein-1 and interleukin-6 after exposure to 9 μg/mL of resveratrol in unstimulated healthy (p = 0.029) and stimulated atopic (p = 0.0075) PBMC. In conclusion, these data confirm the overall lack of cytotoxicity of resveratrol on healthy and atopic PBMC at the tested concentrations. However, at the concentrations tested, there was only a minimal effect of resveratrol on the secretion of HDPs and pro-inflammatory cytokines.

Antimicrobial Potential of Scorpion-Venom-Derived Peptides.

The frequent and irrational use of antibiotics by humans has led to the escalating rise of antimicrobial resistance (AMR) with a high rate of morbidity-mortality worldwide, which poses a challenge to the development of effective treatments. A large number of host defense peptides from different organisms have gained interest due to their broad antibacterial spectrum, rapid action, and low target resistance, implying that these natural sources might be a new alternative to antimicrobial drugs. As important effectors of prey capture, defense against other animal attacks, and competitor deterrence, scorpion venoms have been developed as important candidate sources for modern drug development. With the rapid progress of bioanalytical and high throughput sequencing techniques, more and more scorpion-venom-derived peptides, including disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs), have been recently identified as having massive pharmacological activities in channelopathies, pathogen infections, and cancer treatments. In this review, we summarize the molecular diversity and corresponding structural classification of scorpion venom peptides with antibacterial, antifungal, and/or antiparasitic activity. We also aim to improve the understanding of the underlying mechanisms by which scorpion-venom-derived peptides exert these antimicrobial functions, and finally highlight their key aspects and prospects for antimicrobial therapeutic or pharmaceutical application.

Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnel

The antimicrobial resistance crisis along with challenges of antimicrobial discovery revealed the vital necessity to develop new antibiotics. Many of the animal proline-rich antimicrobial peptides (PrAMPs) inhibit the process of bacterial translation. Genome projects allowed to identify immune-related genes encoding animal host defense peptides. Here, using genome mining approach, we discovered a family of proline-rich cathelicidins, named rumicidins. The genes encoding these peptides are widespread among ruminant mammals. Biochemical studies indicated that rumicidins effectively inhibited the elongation stage of bacterial translation. The cryo-EM structure of the Escherichia coli 70S ribosome in complex with one of the representatives of the family revealed that the binding site of rumicidins span the ribosomal A-site cleft and the nascent peptide exit tunnel interacting with its constriction point by the conservative Trp23-Phe24 dyad. Bacterial resistance to rumicidins is mediated by knockout of the SbmA transporter or modification of the MacAB-TolC efflux pump. A wide spectrum of antibacterial activity, a high efficacy in the animal infection model, and lack of adverse effects towards human cells in vitro make rumicidins promising molecular scaffolds for development of ribosome-targeting antibiotics.

Development of Low-Toxicity Antimicrobial Polycarbonates Bearing Lysine Residues.

Antibiotic resistance has been threatening public health for a long period, while the COVID pandemic aggravated the scenario. To combat antibiotic resistance strains, host defense peptides (HDPs) mimicking molecules have attracted considerable attention. Herein, we reported a series of polycarbonates bearing cationic lysine amino acid residues that could mimic the mechanism of action of HDPs and possess broad-spectrum antimicrobial activity. Moreover, those polymers had negligible toxicity toward red blood cells and mammalian cells. The membrane-disruption mechanism endows the lysine-containing polycarbonates with low possibility of resistance development and the fast killing kinetics, making them promising candidates for antimicrobial development.

Gelatin emulsion gels loaded with host defence peptides for the treatment of antibiotic-resistant infections

The surge in multidrug-resistant bacteria against conventional antibiotics is a rapidly developing global health crisis necessitating novel infection management strategies. Host defence peptides (HDPs), also known as antimicrobial peptides (AMPs), offer a promising alternative to traditional antibiotics, but their practical translation is limited by their susceptibility to proteases and potential off-site cytotoxicity. In this paper, we investigate the feasibility of using gelatin emulsion gels (GELs), prepared using a water-in-oil (W/O) method, for the delivery of HDPs DJK-5 and IDR-1018 to improve their clinical utility. DJK-5-loaded GELs exhibited complete eradication of planktonic Methicillin-resistant Staphylococcus aureus (MRSA) at 4 - and 24-h intervals. Similarly, IDR-1018-loaded GELs demonstrated almost complete killing of MRSA and Escherichia coli (E. coli) after 4 h. Importantly, none of the GEL formulations investigated exhibited in vitro cytotoxicity. Overall, these HDP loaded GELs are a promising solution for the treatment of antibiotic-resistant infections.

Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides.

The chemokine receptors CCR1 and CCR5 display overlapping expression patterns and ligand dependency. Here we find that ligand activation of CCR5, not CCR1, is dependent on N-terminal receptor O-glycosylation. Release from O-glycosylation dependency is obtained by increasing CCR5 N-terminus acidity to the level of CCR1. Ligand activation of CCR5, not CCR1, drastically improves in the absence of glycosaminoglycans (GAGs). Ligand activity at both CCR1 and CCR5 is boosted by positively charged/basic peptides shown to interact with acidic chemokine receptor N-termini. We propose that receptors with an inherent low N-terminus acidity rely on post-translational modifications (PTMs) to efficiently compete with acidic entities in the local environment for ligand capture. Although crucial for initial ligand binding, strong electrostatic interactions between the ligand and the receptor N-terminus may counteract following insertion of the ligand into the receptor binding pocket and activation, a process that seems to be aided in the presence of basic peptides. Basic peptides bind to the naked CCR1 N-terminus, not the CCR5 N-terminus, explaining the loss of boosting of ligand-induced signaling via CCR5 in cells incapable of glycosylation.

Host Defense Peptides: Exploiting an Innate Immune Component Against Infectious Diseases and Cancer

Host Defense Peptides: Exploiting an Innate Immune Component Against Infectious Diseases and Cancer

Dietary supplementation of Astragalus flavonoids regulates intestinal immunology and the gut microbiota to improve growth performance and intestinal health in weaned piglets.

Astragali Radix (AS) is a widely used herb in traditional Chinese medicine, with calycosin as its main isoflavonoid. Our previous study discovered that calycosin triggers host defense peptide (HDP) production in IPEC-J2 cells. The aim of this study is to investigate the alleviation effects of AS total flavone and AS calycosin on growth performance, intestinal immunity, and microflora in weaned piglets. Sixty-four piglets were assigned randomly to 4 treatment groups, (1) CON: the basal diet, (2) P-CON: the basal diet plus antibiotics (1 g/kg), (3) AS-TF: the basal diet plus AS total flavone at 60 mg/day per piglet, (4) AS-CA: the basal diet plus AS calycosin at 30 mg/day per piglet. Each treatment consists of 4 replicates with 4 piglets per replicate. Results showed that treatment with AS-TF and AS-CA enhanced average daily growth and average daily feed intake compared to the CON group (P < 0.01), while AS-CA significantly reduced the diarrhea rate (P < 0.05). Both AS-TF and AS-CA significantly increased serum immunoglobulin (Ig) A and IgG levels, with AS-CA further boosting intestinal mucosal secretory IgA levels (P < 0.05). Histological analysis revealed improvements in the morphology of the jejunum and ileum and goblet cell count by AS-TF and AS-CA (P < 0.05). Supplementation of AS-TF and AS-CA promoted the expression of several intestinal HDPs (P < 0.05), and the effect of AS-CA was better than that of AS-TF. In addition, the AS-TF and AS-CA regulated jejunal microbial diversity and composition, with certain differential bacteria genera were showing high correlation with serum cytokines and immunoglobulin levels, suggesting that the intestinal flora affected by AS-TF and AS-CA may contribute to host immunity. Overall, AS CA and AS TF all improved growth performance and health, likely by enhancing nutrition digestibility, serum and intestinal immunity, and intestinal microbial composition. They showed the similar beneficial effect, indicating AS CA appears to be a major compound contributing to the effects of AS TF. This study demonstrated the positive effect of AS flavonoids on weaned piglets and provided a scientific reference for the efficient use of AS products.

Incorporating Single-Copper Sites and Host Defense Peptides into a Nanoreactor for Antibacterial Therapy by Bioinspired Design

A sustainable solution to the dramatic spread of antibiotic resistance threatening public health security is the development of antibiotic-free antimicrobial substances. Inspired by natural host defense mechanisms involving amino-terminal copper−nickel binding motif (ATCUN) antimicrobial peptides (AMPs), we have designed and prepared an artificial complex (Cu@G-AMPs) incorporating single-atom Cu catalysts for antibacterial therapy. The substrate of the complex, formed from guanine doped with abundant heteroatoms, anchored single Cu atoms with a coordination number of 2 and an average bond length of 1.91Å. Interestingly, Cu@G-AMPs, exhibiting Fenton-like catalytic activity, caused the inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by generating and delivering reactive oxygen species (ROS) cargo. Mechanistically, the intrinsic stress response system of MRSA underwent an irreversible collapse when Cu@G-AMPs initiated its offensive program associated with non-specific targets. Furthermore, Cu@G-AMPs, which inherited the immunomodulatory properties of AMPs, sequentially carried out the functions of pulling edge closure, stabilizing granulation tissue, promoting collagen fiber proliferation, alleviating inflammation, and promoting neovascularization in wound areas infected by MRSA. Our results show that Cu@G-AMPs will provide a new perspective on untangling the complex regulatory networks that resistant bacteria have cultivated to deactivate commercial antibiotics.

Antibacterial and Anti-Inflammatory Activity of Branched Peptides Derived from Natural Host Defense Sequences.

Antibiotic resistance is a major global health threat, necessitating the development of new treatments and diverse molecules to combat severe infections and preserve the efficacy of existing drugs. Antimicrobial peptides (AMPs) offer a versatile arsenal against bacteria, and peptide structure branching can enhance their resistance to proteases and improve their overall efficacy. A small library of peptides derived from natural host defense peptides and synthesized in a tetrabranched form was selected against E. coli. Six selected branched peptides were further studied for antibacterial activity against a panel of strains, biofilm inhibition, protease resistance, and cytotoxicity. Their structure was predicted computationally and their mechanism of action was investigated by electron microscopy and by using fluorescent dyes. The peptide BAMP2 showed promise in a mouse skin infection model, indicating the potential for local infection treatment.

The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits H+-ATPases in Target Pathogens.

Human lactoferrin (hLf) is an innate host defense protein that inhibits microbial H+-ATPases. This protein includes an ancestral structural motif (i.e., γ-core motif) intimately associated with the antimicrobial activity of many natural Cys-rich peptides. Peptides containing a complete γ-core motif from hLf or other phylogenetically diverse antimicrobial peptides (i.e., afnA, SolyC, PA1b, PvD1, thanatin) showed microbicidal activity with similar features to those previously reported for hLf and defensins. Common mechanistic characteristics included (1) cell death independent of plasma membrane (PM) lysis, (2) loss of intracellular K+ (mediated by Tok1p K+ channels in yeast), (3) inhibition of microbicidal activity by high extracellular K+, (4) influence of cellular respiration on microbicidal activity, (5) involvement of mitochondrial ATP synthase in yeast cell death processes, and (6) increment of intracellular ATP. Similar features were also observed with the BM2 peptide, a fungal PM H+-ATPase inhibitor. Collectively, these findings suggest host defense peptides containing a homologous γ-core motif inhibit PM H+-ATPases. Based on this discovery, we propose that the γ-core motif is an archetypal effector involved in the inhibition of PM H+-ATPases across kingdoms of life and contributes to the in vitro microbicidal activity of Cys-rich antimicrobial peptides.

Complex of Defense Polypeptides of Wheatgrass (Elytrigia elongata) Associated with Plant Immunity to Biotic and Abiotic Stress Factors.

Plant defense polypeptides play a crucial role in providing plants with constitutive immunity against various biotic and abiotic stressors. In this study, we explored a complex of proteins from wheatgrass (Elytrigia elongata) spikelets to estimate their role in the plant's tolerance to various environmental factors. The current research shows that in vitro protein extracts from E. elongata spikelets possess antifungal activity against certain Fusarium species, which are specific cereal pathogens, at concentrations of 1-2 mg/mL. In this study, we reproduced these antifungal activities using a 4 mg/mL extract in artificial fungal infection experiments on wheat grain (Triticum aestivum) under controlled laboratory conditions. Furthermore, the tested extract demonstrated a protective effect on Saccharomyces cerevisiae exposed to hyper-salinity stress at a concentration of 2 mg/mL. A combined scheme of fractionation and structural identification was applied for the estimation of the diversity of defense polypeptides. Defensins, lipid-transfer proteins, hydrolase inhibitors (cereal bifunctional trypsin/alpha-amylase inhibitors from a Bowman-Birk trypsin inhibitor), and high-molecular-weight disease resistance proteins were isolated from the extract. Thus, wheatgrass spikelets appear to be a reservoir of defense polypeptides. Our findings contribute to a deeper understanding of plant defense proteins and peptides and their involvement in the adaptation to various stress factors, and they reveal the regulatory effect at the ecosystem level.

S100A12 inhibits Streptococcus pneumoniae and aids in wound healing of corneal epithelial cells both in vitro and in vivo

Streptococcus pneumoniae, a leading cause of corneal infections worldwide, are extremely aggressive despite antibiotic sensitivity and exhibit increased resistance towards antibiotics. Antimicrobial peptides are often considered as potent alternatives against antibiotic resistance and here we have investigated the possible roles of S100A12, a host defense peptide, in wound healing and S. pneumoniae infection. S100A12 significantly inhibited growth of S. pneumoniae by disruption of membrane integrity along with increased generation of reactive oxygen species. Additionally, S100A12 accelerated cell migration and wound closure in human corneal epithelial cells and in a murine corneal wound model by activation of EGFR and MAPK signaling pathways.