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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 …

Advances In Antimicrobial Peptide Discovery Via Machine Learning And Delivery Via Nanotechnology, Alexa Sowers, Guangshun Wang, Malcolm Xing, Bingyun Li

Journal Articles: Pathology and Microbiology

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used …

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 …

Population Density And Immune Investment In Different Developmental Stages Of Tenebrio Molitor, Nathan Dennis

The Plymouth Student Scientist

Immune responses are costly, so organisms should invest in immunity when environmental cues indicate a high risk of infection. The density-dependent prophylaxis (DDP) hypothesis proposes that because the risk of infection increases with population density, organisms should invest more in immunity under crowded conditions. The aims of this study were to investigate DDP in the mealworm beetle Tenebrio molitor and to assess whether density-dependent immune investment differs between developmental stages. T. molitor larvae weighing 50-130mg were assigned to either a low-, moderate-, or high-density treatment for 31 days. After which the phenoloxidase (PO) activity, encapsulation and capsule melanisation responses, and …

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. …

Characterization Of The Mature Form Of A Β-Defensin-Like Peptide, Hoa-D1, In The Lobster Homarus Americanus, Giap H. Vu, Daniel Do, Cindy D. Rivera, Patsy S. Dickinson, Andrew E. Christie, Elizabeth A. Stemmler

Biology Faculty Publications

We report on the characterization of the native form of an American lobster, Homarus americanus, β-defensin-like putative antimicrobial peptide, H. americanus defensin 1 (Hoa-D1), sequenced employing top-down and bottom-up peptidomic strategies using a sensitive, chip-based nanoLC-QTOF-MS/MS instrument. The sequence of Hoa-D1 was determined by mass spectrometry; it was found to contain three disulfide bonds and an amidated C-terminus. The sequence was further validated by searching publicly-accessible H. americanus expressed sequence tag (EST) and transcriptome shotgun assembly (TSA) datasets. Hoa-D1, SYVRScSSNGGDcVYRcYGNIINGAcSGSRVccRSGGGYamide (with c representing a cysteine participating in a disulfide bond), was shown to be related to β-defensin-like peptides previously reported …

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 …

Skin Glands Of An Aquatic Salamander Vary In Size And Distribution And Release Antimicrobial Secretions Effective Against Chytrid Fungal Pathogens, Kenzie E. Pereira, Brian I. Crother, David M. Sever, Clifford L. Fontenot, John A. Pojman, Damien B. Wilburn, Sarah K. Woodley

Faculty Publications

© 2018. Published by The Company of Biologists Ltd. Amphibian skin is unique among vertebrate classes, containing a large number of multicellular exocrine glands that vary among species and have diverse functions. The secretions of skin glands contain a rich array of bioactive compounds including antimicrobial peptides (AMPs). Such compounds are important for amphibian innate immune responses and may protect some species from chytridiomycosis, a lethal skin disease caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). While the bioactivity of skin secretions against Bd has been assessed for many amphibian taxa, similar studies are lacking for …

A Study On Transcriptomic Profiling Of Differentially Expressed Genes Relevant To Innate And Adaptive Immune Pathways In Transgenic Rainbow Trout (Oncorhynchus Mykiss) Harboring Cecropin P1 Transgene, Yueh-Chiang Han

Doctoral Dissertations

Introduction of antimicrobial peptide (AMP) genes into fish genome by the transgenic technology provided a promising solution to control fish disease. Cecropin P1, a known porcine originated AMP, had been introduced into the rainbow trout genome for production of transgenic fish by Chiou et al. (2014) in Chen’s laboratory. Repeated, in vivo, challenge studies demonstrated that these transgenic fish exhibited resistant characteristic to infection by microbial pathogens. Here, we hypothesized that cecropin P1 transgene product may not only directly eliminate microbial pathogens, but also indirectly exert immunomodulatory activity in the transgenic hosts to elevate their disease resistance. To address this …

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 …

Evaluation Of Antimicrobial Peptide K9cath In A Murine Model Of Mastitis, Alberto Barreras-Serrano, Alma Rossana Tamayo-Sosa, Víctor Manuel Del Villar-Pérez, Alma Angelina Castellanos-Félix, Gilberto López-Valencia, Luis Tinoco-Gracia, Rogelio Hernández-Pando, Tonatiuh Melgarejo

The Thai Journal of Veterinary Medicine

In the present study the effect of antimicrobial peptide K9CATH was evaluated in a murine model of mastitis by Staphylococcus aureus. Mastitis was induced with a clinical isolate of S. aureus in 20 female Balb/c mice at 7 to 10 days of lactation. Ten mice (treatment group) received daily intramammary infusions of 32 μg/50 μL K9CATH peptide, for 3 consecutive days, and 10 other mice (control group) received only 50 μL of saline solution. Results showed a significant reduction (P<0.01) in S. aureus CFU counts in the treatment group compared to the control group. These data suggest that the K9CATH peptide could be a potential candidate for the treatment of bovine mastitis.

Investigating The Nucleic Acid Interactions Of Histone-Derived Antimicrobial Peptides, Sukin Sim, Penny Wang, Brittany N. Beyer, Kara J. Cutrona, Mala L. Radhakrishnan, Donald E. Elmore

Faculty Research and Scholarship

While many antimicrobial peptides (AMPs) disrupt bacterial membranes, some translocate into bacteria and interfere with intracellular processes. Buforin II and DesHDAP1 are thought to kill bacteria by interacting with nucleic acids. Molecular modeling and experimental measurements were used to show that neither nucleic acid binding peptide selectively binds DNA sequences. Simulations and experiments also showed that changing lysines to arginines enhances DNA binding, suggesting that including additional guanidinium groups is a potential strategy to engineer more potent AMPs. Moreover, the lack of binding specificity may make it more difficult for bacteria to evolve resistance to these and other similar AMPs.

Porphyrin-Modified Antimicrobial Peptide Indicators For Detection Of Bacteria, Brandy J. Johnson, Chris R. Taitt, Apre Gleaves, Stella H. North, Anthony P. Malanoski, Iwona A. Leska, Edikan Archibong, Stormie M. Monk

United States Navy: Publications

This study demonstrates the potential of porphyrin modified antimicrobial peptides for indication of bacterial targets on the basis of changes in the spectrophotometric characteristics of the construct. Detection is a result of changes in the structure of the antimicrobial peptide upon target binding. Those constructs comprised of peptides that offer little or no change in conformation upon interaction with bacterial cells demonstrated negligible changes in absorbance and fluorescence when challenged using Escherichia coli or Bacillus cereus. CD analysis confirms the presence/absence of conformational changes in the porphyrin-peptide constructs. Differing spectrophotometric responses were observed for constructs utilizing different peptides. The …

The Effects Of Environmental Pollutants On Adipogenesis In The 3t3-L1 Model, Jing Wang

Biology Dissertations

Humans are continuously exposed to mixtures of environmental pollutants. Polycyclic aromatic hydrocarbons (PAHs), such as 2-naphthol, and heavy metals, such as lead, are some of these pollutants. Results from epidemiological studies show associations between exposure to 2-naphthol, exposure to lead, and obesity. However, the individual and combined effects of 2-naphthol and lead on fat cell development (adipogenesis) have not been directly characterized in a biological system. In this study, we evaluated the effects of 2-naphthol and/or lead on adipogenesis using mouse 3T3-L1 cells.

Cells were exposed to different doses of 2-naphthol and/or lead. Induced terminal differentiation was evaluated by cell …

Development Of A Modified Calcium-Based Composite Ceramic Bone Graft Material, Gavin Buckholtz

Electronic Theses and Dissertations

Composites consisting of both calcium aluminum oxide and hydroxyapatite were tested for their applicability as bone replacement scaffolds. Implanted bone scaffolds may fail due to a variety of reasons, including mechanical and biological failure. Mechanical failure may occur as a result of dissimilar properties between the surrounding healthy bone and the scaffold. Biological failure can occur due to integration problems at the interface of the scaffold and the natural bone, or as a result of implant associated infections as a result of bacterial attachment and biofilm formation. Calcium aluminum oxide:hydroxyapatite composites were developed that address these three modes of implant …

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. …

Characterization Of Carbapenemase Producer Enterobacteriaceae Isolated In The United Arab Emirates, Amna Eisa Al Baloushi

Dissertations

The efficient control of the spread of carbapenemase producer Enterobacteriaceae, a major public health treat world-wide, requires knowledge on the molecular epidemiology and genetic background of the emerging carbapenemase genes.

Our aim was to investigate the genetic support of New Delhi metallo-beta-lactamase and OXA-48-type carbapenemase genes in carbapenem resistant Enterobacteriaceae isolated in the United Arab Emirates. Since these isolates are extremely drug resistant, leaving few treatment options, the efficacy of alternative antimicrobials was also assessed.

Seven NDM-producer Enterobacteriaceae, collected during 2009-2011, and subsequently five NDM and OXA-48-type carbapenemase co-producer Klebsiella pneumoniae isolated during 2011-2013 in three hospitals of the …

Antimicrobial Peptides In 2014., Guangshun Wang, Biswajit Mishra, Kyle Lau, Tamara Lushnikova, Radha Golla, Xiuqing Wang

Journal Articles: Pathology and Microbiology

This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release …

Antimicrobial Peptides For Use In Oyster Aquaculture: Effect On Pathogens, Commensals, And Eukaryotic Expression Systems, Tarquin Dorrington, Marta Gomez-Chiarri

Marta Gomez-Chiarri

Two antimicrobial peptides (AMPs) of marine origin, tachyplesin from the Japanese horseshoe crab, Tachypleus tridentatus, and pleurocidin-amide from the winter flounder, Pseudopleuronectes americanus, were tested for their potential effectiveness in disease treatment in oyster aquaculture. Tachyplesin had a greater antimicrobial effect than pleurocidin-amideagainst a range of gram-positive and gram-negative bacteria, with minimum inhibitor concentrations in the range of 0.625 to 5ug mL–1. Tachyplesin (50 mg mL–1) was also more effective than pleurocidin-amide (250 mg mL–1) against the oyster protozoan parasite Perkinsus marinus, reducing its viability to 9% versus 22% in vitro. Both peptides were unaffected by variations in pH and …

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 …