Life Sciences Commons^™

Exploring The Design Space Of Antifungal Peptides, Miryam Kikhwa

Seton Hall University Dissertations and Theses (ETDs)

The synthesis, characterization, and evaluation of antifungal activity of peptides FQ15 and FG10 will be conducted to address the hypothesis. The hypothesis of this thesis is that a peptide with similar properties to AS15 would have similar activity against Cryptococcus neoformans. This study addresses the challenge of drug- resistant microbes by developing inhibitors targeting lipid flippase and exploring their potential as antimicrobial agents against Cryptococcus neoformans. Chapter 1 provides a historical context of the background on the development of antimicrobials and common antifungal treatments, as well as an introduction about C. neoformans and its resistance mechanism. Chapter 2 introduces the …

Turbidimetric Bioassays: A Solution To Antimicrobial Activity Detection In Asymptomatic Bacteriuria Isolates Against Uropathogenic Escherichia Coli, Ciara Kenneally, Craig P. Murphy, Roy D. Sleator, Eamonn P. Culligan

Department of Biological Sciences Publications

Traditional bacteriocin screening methods often face limitations due to diffusion-related challenges in agar matrices, which can prevent the peptides from reaching their target organism. Turbidimetric techniques offer a solution to these issues, eliminating diffusion-related problems and providing an initial quantification of bacteriocin efficacy in producer organisms. This study involved screening the cell-free supernatant (CFS) from eight uncharacterized asymptomatic bacteriuria (ABU) isolates and Escherichia coli 83972 for antimicrobial activity against clinical uropathogenic E. coli (UPEC) strains using turbidimetric growth methods. ABU isolates exhibiting activity against five or more UPEC strains were further characterized (PUTS 37, PUTS 58, PUTS 59, S-07-4, and …

A Rationally Designed Antimicrobial Peptide From Structural And Functional Insights Of Clostridioides Difficile Translation Initiation Factor 1, Elvira Alanis, Faith Aguilar, Niaz Banaei, Frank B. Dean, Alexa Villarreal, Miguel Alanis, Karen Lozano, James M. Bullard, Yonghong Zhang

School of Integrative Biological and Chemical Sciences Faculty Publications and Presentations

ABSTRACT: A significant increase of hospital-acquired bacterial infections during the COVID-19 pandemic has become an urgent medical problem. Clostridioides difficile is an urgent antibiotic-resistant bacterial pathogen and a leading causative agent of nosocomial infections. The increasing recurrence of C. difficile infection and antibi­otic resistance in C. difficile has led to an unmet need for the discovery of new com­pounds distinctly different from present antimicrobials, while antimicrobial peptides as promising alternatives to conventional antibiotics have attracted growing interest recently. Protein synthesis is an essential metabolic process in all bacteria and a validated antibiotic target. Initiation factor 1 from C. difficile (Cd-IF1) …

Liquid Chromatography Mass Spectrometry Method Development For The Determination Of Β–Defensins In Bovine Milk, Elisha Ogbebor

Masters Theses & Specialist Projects

Bovine mastitis is caused by a wide range of pathogens which results in a substantial economic loss for the dairy cattle livestock industry. β-defensins are a part of the innate immune system and act as the first line of defense against mastitis in bovine. β-defensins (~6- 10kDa) are antimicrobial peptides that contain about 28 to 67 amino acids, the presence of six cysteine residues results in their three disulfide bonds and a β-sheet structure. A few β- defensins have been identified in cows based on the site of occurrence and time of expression in tissue, but not in milk. A …

Optimization Of Ultrasound-Assisted Extraction Process Of Antimicrobial Peptides From The By-Products Of Mytilus Edulis, Yue Zhang, Yu-Xia Yang, Guang-Yu Shi, Xin-Zhi Zhao, Yuan-Bo Pan, Qiong-Yi Xu

Food and Machinery

The use of ultrasonic-assisted acetate extraction to improve the efficiency of the conventional acetate extraction technique with the aim of extracting antimicrobial peptides from Mytilus edulis by-product using acetate solution was investigated. Based on the single factor experiment, response surface methodology was used to optimize experimental conditions for extraction of antimicrobial peptides. The optimum extraction conditions for maximum antimicrobial peptide yield were established to be ultrasonic power of 200 W, acetate concentration of 0.8%, liquid-material ratio of 6∶1 (mL/g), and ultrasonic extraction time of 16 min. Under abovementioned conditions, the yield and the zone of inhibition against Staphylococcus aureus were …

Optimization Of Extraction Process And Activity Study Of Antimicrobial Peptides From Pleurotus Tuber-Regium Mycelium, Zhang Shu-Hui, Luo Lu, Sun Xue-Yan, Ma Ai-Min

Food and Machinery

Objective: To improve the yield and antibacterial rate of antimicrobial peptides from Pleurotus tuber-regium mycelium (PTRM-AMPs). Methods: Taking the yield and the antibacterial rate of PTRM-AMPs against Staphylococcus aureus and Esche-richia coli as evaluation indexes, on the basis of protease screening, the extraction process of PTRM-AMPs was optimized, and the minimum inhibitory concentration of PTRM-AMPs was determined. Results: The optimum technological conditions for the preparation of PTRM-AMPs by alkaline protease hydrolysis were as follows: the enzymatic hydrolysis temperature was 39.5 ℃, the enzymatic hydrolysis time was 3.2 h, the pH value was 11.1, the solid-liquid ratio was …

Characterization Of Genetic Pathways Involved In Resistance To A Novel Antifungal Peptide, Kayla L. Haberman

Graduate Theses and Dissertations

Antibiotic resistance is increasing prevalence, particularly in Candida glabrata. This opportunistic pathogen is closely phylogenetically related to Saccharomyces cerevisiae; however, its characterization is limited. C. glabrata is only second to Candida albicans as a fungal pathogen in immunocompromised patients. Commonly resistant to azoles, the most common fungal therapy, it has become costly and challenging to treat. A histatin 5 derived antifungal peptide, KM29, has a high degree of efficacy in Candida species and S. cerevisiae. The objective of this work is to advance our understanding of the mechanism of action of KM29 against C. glabrata. Previous work in the lab …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Chga-Depleted Urothelial Amp And Immune Response During Urinary Tract Infection, Theadora Jane Ceccarelli

Master's Theses

Women are 8 times more likely than men to experience a urinary tract infection (UTI) with up to 60% of women reporting a UTI in their lifetime. This significant healthcare burden is caused by the infection of uropathogenic Escherichia coli in the urinary tract. At this time, treatment is limited to antibiotic therapy, which is challenged by antibiotic-resistance. These factors make UTIs an NIH priority and are motivation for our research.CgA is a protein of the granin family co-released with catecholamines from neuroendocrine cells throughout the body. Pro-hormone convertases post-translationally cleave CgA into peptides, like catestatin, which can have antimicrobial …

Antimicrobial Peptide Development: From Massively Parallel Peptide Sequencing To Bioinformatic Motif Identification, Alexander K. Erikson

Theses and Dissertations

The isolation, purification, and clinical deployment of antibiotics is one of the major drivers of decrease in morbidity and mortality from infectious bacteria in the 20th century. The rapid, ubiquitous deployment of antibiotics encouraged swift development and distribution of antibiotic resistance. New, novel techniques, technologies, and ultimately therapeutic antimicrobial compounds will be required to counter the rise of antibiotic resistant microbes. Historically, mimicking naturally occurring compounds has been the most fruitful method for discovering new antibiotics; unsurprisingly, many recent efforts have focused on expanding the cultivation and detection of previously unknown microbes and compounds, respectively. Other techniques explore developing compounds …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

Antimicrobial Peptide Identification Using Multi-Scale Convolutional Network, Xin Su, Jing Xu, Yanbin Yin, Xiongwen Quan, Han Zhang

Department of Food Science and Technology: Faculty Publications

Background: Antibiotic resistance has become an increasingly serious problem in the past decades. As an alternative choice, antimicrobial peptides (AMPs) have attracted lots of attention. To identify new AMPs, machine learning methods have been commonly used. More recently, some deep learning methods have also been applied to this problem.

Results: In this paper, we designed a deep learning model to identify AMP sequences. We employed the embedding layer and the multi-scale convolutional network in our model. The multi-scale convolutional network, which contains multiple convolutional layers of varying filter lengths, could utilize all latent features captured by the multiple convolutional layers. …

Exploration Of Antimicrobial Activity In Natural Peptides And High-Throughput Discovery Of Synthetic Peptides, Emma Kay Dallon

Theses and Dissertations

Despite many medical advances, antibiotic resistant bacteria increasingly plague the modern world, necessitating discovery of new antibiotics. One area of nature that can provide inspiration for antibiotics is antimicrobial peptides. Many of these peptides exist in nature, with some classes that have not been studied or characterized well. One such class is the defensin-like peptides generated by the plant Medicago truncatula as part of their symbiotic relationship with Sinorhizobium meliloti. Nodule-specific Cysteine Rich (NCR) peptides are defined by the presence of multiple cysteines, and regulate the growth of S. meliloti within plant cells. While some of these NCR peptides have …

Investigating Peroxiredoxins Impact On Amps, Noah Earland

SMU Journal of Undergraduate Research

The Orr-Radyuk lab is interested in understanding the link between aging and genetic influences controlling the cell’s redox state, as determined by enzymes involved in reducing and oxidizing (redox) reactions. They have observed that Drosophila normally exhibit a shift towards a pro-oxidizing cellular environment and spikes in AMP levels, independent of infections, when they reach old age. Additionally, peroxiredoxins (PRXs), a family of thiol-dependent peroxidases, have been shown to impact lifespan, and regulate the same pro-oxidizing shift seen in advanced age. Beyond their peroxidase functions, RXRs can also interact with signaling pathways related to immunity. Previous data showed that PRXs …

The Effects Of Gamma Irradiation Sterilization, Temperature, And Ph On The Antimicrobial Activity Of Epinecidin-1, Han-Ning Huang, Chang-Jer Wu, Jyh-Yih Chen

Journal of Marine Science and Technology

This study examined how different processing conditions affected the antibacterial activity of epinecidin-1 alone or in combination with deionized distilled water or KY jelly and evaluated its activity against methicillin resistant Staphylococcus aureus (MRSA) in a product development pipeline. High temperature and γ-irradiation (25 kGy) decreased antimicrobial activity of epinecidin-1, as determined by measuring minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). However, epinecidin-1 exhibited high antimicrobial activity under low pH conditions. The pH stability and the wide spectrum of action against methicillin resistant Staphylococcus aureus (MRSA) may make epinecidin-1 peptide a suitable drug candidate. This research demonstrates the …

Determining Antimicrobial Activity In Hydrolysates Obtained From Buttermilk Substrates By Trypsin And Pepsin, Deborah Kim, Karen Ramun, Stephanie Carpintero, Suyapa Padillo, Antonio-Jose Trujillo, Rafael Jimenez-Flores

STAR Program Research Presentations

Milk proteins within their structure and sequence, contain peptides that exhibit antithrombotic, immunomodulatory, antimicrobial, antihypertensive, and other bioactivities. These peptides are released as the enzymes cleave milk proteins at certain locations of the amino acid chains. In this research, four different substrates were hydrolyzed with the gastrointestinal enzymes, pepsin and trypsin. The substrates were buttermilk (BM) and whey buttermilk (WBM), which are waste products of butter and cheese production, and supercritical CO₂ fluid (SFE) treated buttermilk (S-BM) and whey buttermilk (S-WBM). SFE acts as a solvent which removes triglycerides from the substrates and changes the overall composition of samples. …

Design, Development, And Characterization Of Novel Antimicrobial Peptides For Pharmaceutical Applications, Yazan H. Akkam

Graduate Theses and Dissertations

Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs. Histatin 5 is a naturally occurring human salivary antifungal peptide and the first line of defense against infections of the oral cavity. This research has focused on understanding the activity of histatin 5, and subsequently designing novel peptides that may serve as models for the further development of therapeutics to treat fungal infection.

This objective has been achieved in three steps: studying the structural requirement of histatin 5 involved in antifungal activity, the identification of …

Investigation Of Ll-37-Mediated Sirna Transfection, Mustafa Yalçinkaya, Şahru Yüksel

Turkish Journal of Biology

RNA interference is not only an important tool for studying protein function; it also holds many promises for the treatment of a variety of diseases in which the function of unwanted proteins needs to be suppressed. For small interfering RNA (siRNA) to be used as a therapeutic agent, the biggest hurdle is to find the right delivery agent that is both nontoxic to the cells and efficient in delivery. Synthetic and natural peptides from a variety of organisms have been investigated for this purpose. However, there is still no agent or formulation that has been approved for siRNA delivery. Antimicrobial …

Effect Of Dietary Antibacterial Peptide And Zinc-Methionine On Performance And Serum Biochemical Parameters In Piglets, J. H. Wang, C. C. Wu, J. Feng

Biochemistry Collection

The objective of this study was to evaluate the effect of dietary supplementation of antibacterial peptide and zinc methionine on performance and some serum biochemical parameters of weaned piglets. Rongchang male piglets (28 days of age, initial weight 8.4 ± 0.65 kg) were used. All piglets were randomly allotted to four diets including the control group, the antibacterial peptide (AP) group containing 10 mg antibacterial peptide/kg diet, the zinc methionine (Zn-Met) group with 1 200 zinc methionine/kg diet (equal to 200 mg Zn²⁺/kg diet), the zinc methionine/antibacterial peptide (Zn/AP) group containing 10 mg antibacterial peptide and 1 200 …

A Fourier Transformation Based Method To Mine Peptide Space For Antimicrobial Activity, Vijayaraj Nagarajan, Navodit Kaushik, Beddhu Murali, Chaoyang Zhang, Sanyogita Lakhera, Mohamed O. Elasri, Youping Deng

Faculty Publications

Background

Naturally occurring antimicrobial peptides are currently being explored as potential candidate peptide drugs. Since antimicrobial peptides are part of the innate immune system of every living organism, it is possible to discover new candidate peptides using the available genomic and proteomic data. High throughput computational techniques could also be used to virtually scan the entire peptide space for discovering out new candidate antimicrobial peptides.

Result

We have identified a unique indexing method based on biologically distinct characteristic features of known antimicrobial peptides. Analysis of the entries in the antimicrobial peptide databases, based on our indexing method, using Fourier transformation …

Effect Of Astragalus And Astragalus Polysaccharide On Antimicrobial Peptides Pr-39 And Protegrin-1 Gene Expression In Pigs, Youjin Tu, Yizhen Wang, Chunlan Xu, Guojia Yao, Tizhong Shan

Turkish Journal of Veterinary & Animal Sciences

This experiment was conducted to study the effects of micron Astragalus, 80 mesh Astragalus and Astragalus polysaccharide (APS) on antimicrobial peptides PR-39 and protegrin-1 gene expression in pigs using semi-quantitative RT-PCR analysis. One hundred twenty 60-day-old Duroc x Landrace x Yorkshire piglets (21.88 ± 1.26 kg of average initial body weight) were randomly allotted to 4 treatments. Each treatment had 3 replicates (i.e. pens) with 10 pigs per pen. The basal diets were supplemented with 0, 5 g kg^{-1} APS, 5 g kg^{-1} 80 mesh Astragalus, and 5 g kg^{-1} micron Astragalus, respectively, and the feeding experiment lasted 30 days. …

Identification Of A Defensin From The Hemolymph Of The American Dog Tick, Dermacentor Variabilis, Robert Johns, Daniel E. Sonenshine, Wayne L. Hynes

Biological Sciences Faculty Publications

Hemolymph from partially fed virgin Dermacentor variabilis females was collected following Borrelia burgdorferi challenge and assayed for antimicrobial activity against Bacillus subtilis and B. burgdorferi. A small inducible cationic peptide was identified by SDS-PAGE in the hemolymph of these ticks as early as 1h post challenge. Following purification by a three-step procedure involving sequential SepPak elution, reversed phase high performance liquid chromatography (RP-HPLC) and gel electrophoresis, the yield of the active peptide was approximately 0.1% of the total protein in the hemolymph plasma. The molecular weight, 4.2kDa, was determined by MALDI-TOF mass spectrometry. N-terminal sequencing by the Edman degradation …