DOCSLIB.ORG

Timothy Moore Dissertation 4 October 2013.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Timothy Moore Dissertation 4 October 2013.Pdf Novel Approach for Assessment and Mitigation of Heat-Stress Adverse Effects by Timothy Moore A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama December 14, 2013 Keywords: heat stress, gut microflora, probiotics, erythrocyte vesiculation, light microscopy Copyright 2013 by Timothy Moore Approved by David Pascoe, Co-chair, Distinguished Professor of Kinesiology Vitaly Vodyanoy, Co-chair, Professor of Anatomy, Physiology and Pharmacology Iryna Sorokulova, Professor of Microbiology Mary Rudisill, Distinguished Professor of Kinesiology Abstract We have characterized the efficacy of a Bacillus subtilis probiotic strain for the prevention of heat stress-related complications in rats. It has been shown that pre-treatment of rats with probiotic bacteria prevented microbial translocation from the gut into mesenteric lymph nodes and liver. Heat stressed animals without probiotic treatment had a high level of lipopolysaccharides (LPS) in the blood. In contrast, animals in the probiotic group, exposed to the same level of heat did not show elevation of LPS levels. Additionally, cytokine IL-10 concentration significantly increased in stressed animals without probiotic pretreatment, whereas administration of probiotic treatment before heat stress normalized the level of IL-10. We also found that the elevation of the temperature of the blood during heat stress causes an increase in the shedding of erythrocyte membrane vesicles. The elevation of temperature from 36.70.3 to 40.30.4 o C resulted in a significant increase of the concentration of vesicles in blood. At a temperature of 37 o C, mean vesicle concentrations found in rat blood was (1.40.2)×106 vesicles/μL, while after exposure to heat the concentration increased to (3.80.3)×106 vesicles/μL in the group of animals without probiotic treatment. Treatment with the probiotic before heat stress prevented vesiculation of erythrocytes in animals. The results have shown a high efficacy of the probiotic B. subtilis in the prevention of heat stress- related complications in rats. Additionally, the images of human erythrocytes and associated vesicles have been analyzed by a light microscopy system with spatial resolution of better than 90 nm. The samples were observed in an aqueous environment and required no freezing, dehydration, staining, shadowing, ii marking or any other form of manipulation. Temperature elevation has resulted in a significant increase in the concentration of structurally transformed erythrocytes (echinocytes) and vesicles in the blood. The process of vesicle separation from spiculated erythrocytes has been video recorded in real time. Accurate accounting of vesicle numbers and dimensions suggest that 86% of the lost erythrocyte material is lost not by vesiculation but by another, as yet - unknown mechanism. The increase in the number of vesicles associated with elevated temperatures may be indicative of the individual’s heat stress level and thereby serve as diagnostic test of erythrocyte stability and heat resistance and level of heat adaptation. iii Acknowledgments The author wishes to express his deep thanks to Dr. David Pascoe, Dr. Vitaly Vodyanoy, Dr. Iryna Sorokulova and Dr. Mary Rudisill for their support, encouragement and guidance during his doctoral program. The author also wishes to thank Oleg Pustovyy and Ludmila Globa for their many hours of laboratory support. Lastly, the author wishes to thank his wife Robin and sons – Christopher, Nicholas and Johnathon - for their love and patience throughout his graduate program and especially during the development of this manuscript. iv Table of Contents Abstract ........................................................................................................................................... ii Acknowledgments.......................................................................................................................... iv List of Tables ................................................................................................................................ vii List of Figures .............................................................................................................................. viii 1. Introduction ................................................................................................................................. 1 2. Literature review ......................................................................................................................... 4 2.1 Passive and exercise-induced heat stress .............................................................................. 4 2.2 Heat stress complications ...................................................................................................... 6 2.2.1 Gastrointestinal Changes ................................................................................................ 6 2.2.2 Beneficial bacteria .......................................................................................................... 7 2.2.3 Changes in blood ............................................................................................................ 9 3.3 Vesicles in human and animal blood..................................................................................... 9 3.3.1 History of vesicles in blood ............................................................................................ 9 3.3.2 Vesicles, exosomes, and ectosomes. ............................................................................ 11 3.3.3 Origin of vesicles in blood............................................................................................ 12 3.3.4 Role and clinical significance of vesicles ..................................................................... 12 3.3.5 Composition of vesicles ................................................................................................ 13 3.3.6 Morphology of vesicles ................................................................................................ 13 3.3.7 Induction of vesicle production and shedding .............................................................. 14 3.3.8 Vesicles related to intestinal cells ................................................................................. 15 3.3.9 Vesicles related to heat shock proteins at exercise and hyperthermia .......................... 15 3.4 Vesicles generated by red blood cell ................................................................................... 16 3.4.1 History of red blood cells discovery ............................................................................. 16 3.4.2 General properties of red blood cells ............................................................................ 19 3.4.3 Life, aging and death of red blood cells ....................................................................... 20 3.4.4 Erythrocyte membrane ................................................................................................. 23 3.4.5 Red blood cell discocyte-echinocite transformations ................................................... 31 3.4.6 Vesicles released by red blood cells at normal conditions ........................................... 34 3.4.7 Red blood cell vesicles at elevated temperature ........................................................... 37 3.4.8 Vesicles originating from red blood cells during storage ............................................. 45 3.4.9 Diagnostic value of red blood cell vesicles .................................................................. 46 3.5. Light microscopy of the native blood ............................................................................. 47 4. Hypotheses ................................................................................................................................ 55 5. Objectives ................................................................................................................................. 55 5.1 Main Goals .......................................................................................................................... 55 5.2 Specific aims of this research are: ....................................................................................... 55 6. Results ....................................................................................................................................... 57 v 6.1 Article 1. Antagonistic activity of bacillus bacteria against food-borne pathogens (Article is accepted for publication in the Journal of Probiotics & Health) .................................... 57 6.2. Article 2. Bacillus Probiotic for Prevention of Heat Stress-Related Complications (manuscript is prepared for publication). ........................................................................... 86 6.3 Article 3. Microscopic evaluation of vesicles shed by erythrocytes at elevated temperatures (Article is accepted for publication in the Microscopy Research and Techniques) ......... 980 6.4 Article 4. Microscopic evaluation of vesicles shed by rat erythrocytes at elevated temperatures (Article is accepted for publication in the Journal of Thermal Biology) .... 123 7. Conclusions ............................................................................................................................. 143 8. Bibliography ..........................................................................................................................
Load more

Recommended publications
  • Harnessing the Power of Bacteria in Advancing Cancer Treatment
    International Journal of Molecular Sciences Review Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment Shruti S. Sawant, Suyash M. Patil, Vivek Gupta and Nitesh K. Kunda * Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Jamaica, NY 11439, USA; [email protected] (S.S.S.); [email protected] (S.M.P.); [email protected] (V.G.) * Correspondence: [email protected]; Tel.: +1-718-990-1632 Received: 20 September 2020; Accepted: 11 October 2020; Published: 14 October 2020 Abstract: Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.
    [Show full text]
  • Molecular Analysis of Candidate Probiotic Effector Molecules of Lactobacillus Plantarum
    Molecular analysis of candidate probiotic effector molecules of Lactobacillus plantarum Daniela Maria Remus Thesis committee Promoter Prof. dr. Michiel Kleerebezem Professor of Bacterial Metagenomics Wageningen University Co-promoter Dr. Peter A. Bron Senior Scientist, NIZO food research BV, Ede Other members Prof. dr. Tjakko Abee, Wageningen University Prof. dr. Pascal Hols, University of Lovain (Lovain la Neuve), Belgium Dr. Philippe Langella, National Institute of Agricultural Research (INRA), Paris, France Prof. dr. Roland J. Siezen, Radboud University, Nijmegen This research was conducted under the auspices of the Graduate School VLAG (Advanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Molecular analysis of candidate probiotic effector molecules of Lactobacillus plantarum Daniela Maria Remus Thesis submitted in fulfillment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Tuesday 09 October 2012 at 4 p.m. in the Aula. Daniela Maria Remus Molecular analysis of candidate probiotic effector molecules of Lactobacillus plantarum Ph.D. Thesis, Wageningen University, Wageningen, The Netherlands (2012) With references and summaries in English and Dutch. ISBN 978-94-6173-373-3 Summary Lactobacilli occupy diverse natural habitats, including dairy products and the mammalian gastrointestinal (GI) tract, and several Lactobacillus strains are marketed as probiotics that can interact with host cells in the GI tract by which they are proposed to beneficially influence the health status of their consumers. The discovery of probiotic effector molecules is instrumental to understand the exact modes of probiotic action, which is required for their controlled, safe, and purpose-directed application.
    [Show full text]
  • Plantaricin KW30
    The Molecular and Cellular Characterisation of the First Glycocin: Plantaricin KW30 Judith Stepper 2009 The Molecular and Cellular Characterisation of the First Glycocin: Plantaricin KW30 A thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry at Massey University, Palmerston North, New Zealand Judith Stepper 2009 “What we know is a drop. What we don’t know is an ocean.” Isaac Newton (1643 – 1727) ABSTRACT Bacteriocins, typically secreted by Gram-positive and -negative bacteria, are ribosomally- synthesised antimicrobial peptides which inhibit the growth of competing bacteria. We have purified a 43 amino acid bacteriocin, plantaricin KW30 (PlnKW30) produced by Lactobacillus plantarum KW30, that has little amino acid sequence similarity to any other characterised bacteriocin. The gene encoding plnKW30 is in a cluster with the genes required for maturation and export of, and immunity to, the bacteriocin. This arrangement of genes is similar to the genomic context of bacteriocin genes in other lactic acid bacteria. The plnKW30 gene cluster comprises six genes encoding a glycosyltransferase, a proteolytic ABC-transporter, two putative thioredoxins, a response regulator and PlnKW30 itself. PlnKW30 was found to possess two unusual post-translational modifications: an O-glycosylated serine and an unprecedented S-glycosylation of the C-terminal cysteine. The modified serine is located on an eight residue loop that is tethered by a disulfide bridge. Both modifications have been identified as N-acetylglucosamines (GlcNAc), making PlnKW30 the first described class IV bacteriocin. A post-translational modification with S-linked GlcNAc is unprecedented in bacteriocins as well as in all genera.
    [Show full text]
  • The Bacteriostatic Diglycocylated Bacteriocin Glycocin F Targets A
    Copyright is owned by the Author of the thesis. Permission is given for a copy to be downloaded by an individual for the purpose of research and private study only. The thesis may not be reproduced elsewhere without the permission of the Author. The Bacteriostatic Diglycosylated Bacteriocin Glycocin F Targets a Sugar-Specific Transporter A thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry at Massey University, Manawatu New Zealand Kelvin Ross Drower 2014 Dedicated to Nana and Pop Abstract The increasing prevalence of antibiotic-resistance bacteria is threatening to end the antibiotic era established following Alexander Fleming's discovery of penicillin in 1928. Over-prescription and misuse of broad-spectrum antibiotics has hastened the development and spread of antibiotic resistance. This, combined with a lack of research and development (R&D) of new antibiotics by major pharmaceutical companies, may lead to a widespread recurrence of 'incurable' bacterial diseases. However while commercial R&D of antibiotics has waned, much research has been carried out to characterise bacteriocins, ribosomally-synthesised antimicrobial polypeptides thought to be produced by virtually all prokaryotes. Although hundreds of bacteriocins have been identified and characterised, only a handful of their cognate receptors on susceptible cells have been identified. Glycocin F is a bacteriostatic diglycosylated 43-amino acid bacteriocin produced by the Gram-positive bacterium Lactobacillus plantarum KW30 that inhibits the growth of a broad range of bacteria. The mechanism of action of glycocin F is unknown, however evidence suggested that glycocin F binds to cells via a N-acetylglucosamine (GlcNAc) specific phosphoenolpyruvate:carbohydrate-phosphotransferase system (PTS) transporter, as had been shown for lactococcin A, lactococcin B and microcin E492 that target a mannose specific PTS transporter.
    [Show full text]
  • UC Berkeley Electronic Theses and Dissertations
    UC Berkeley UC Berkeley Electronic Theses and Dissertations Title Interactions of Microbes in Communities Permalink https://escholarship.org/uc/item/2hg5h7k6 Author Sczesnak, Andrew Publication Date 2018 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California Interactions of Microbes in Communities By Andrew Sczesnak A dissertation submitted in partial satisfaction of the requirements for the degree of Joint Doctor of Philosophy with University of California, San Francisco in Bioengineering in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Adam P. Arkin, Chair Professor Matthew Traxler Professor Michael Fischbach Fall 2018 Abstract Interactions of Microbes in Communities By Andrew Sczesnak Joint Doctor of Philosophy with University of California, San Francisco in Bioengineering University of California, Berkeley Professor Adam P. Arkin, Chair Groups of microorganisms sharing an environment (microbial communities) are ubiquitous in nature. Microbial communities provide essential ecosystem services to other life on Earth by e.g., participating in global biogeochemical processes or interacting with a host’s immune system. Such microbes compete for scarce resources, modify an environment for their own purposes, actively war, and occasionally cooperate. Though numerous studies have surveyed the diversity of microbial life in different environments, few have determined the ways in which members of microbial communities interact with one another. Understanding the ways and means by which microbes interact is essential if we are to understand how microbial communities form, persist, and change over time. Knowledge of these processes will allow us to rationally design microbial communities to perform useful functions and predict how our actions might shift the balance of microbes in a community, and thus affect its function.
    [Show full text]
  • Produced by Bacillus Amylo- Liquefaciens Isolated From
    RESEARCH ARTICLE INTERNATIONAL MICROBIOLOGY (2006) 9:111-118 www.im.microbios.org Márcia P. Lisboa1 Characterization of a Diego Bonatto2 Delmar Bizani1 bacteriocin-like substance João A.P. Henriques3 produced by Bacillus amylo- Adriano Brandelli1* liquefaciens isolated from 1Department of Science Food, the Brazilian Atlantic forest ICTA, Federal University of Rio Grande do Sul, Porto Alegre, Brazil 2Biotechnology Institute, University of Caxias do Sul, Brazil 3Biotechnology Center, Federal University of Rio Grande do Sul, Summary. A Bacillus strain producing a bacteriocin-like substance was charac- Porto Alegre, Brazil terized by biochemical profiling and 16S rDNA sequencing. Phylogenetic analysis indicated that the strain has high sequence similarity with Bacillus amyloliquefa- ciens. The antimicrobial substance was inhibitory to pathogenic and food-spoilage bacteria, such as Listeria monocytogenes, Bacillus cereus, Serratia marcescens, and Pasteurella haemolytica. It was stable over a wide temperature range, but lost activity when the temperature reached 121°C/15 min. Maximum activity was observed at acidic and neutral pH values, but not at alkaline pH. The antimicrobial Received 18 February 2006 substance was sensitive to the proteolytic action of trypsin, papain, proteinase K, Accepted 17 May 2006 and pronase E. Except for iturins, other antimicrobial peptides have not been des- *Corresponding author: cribed for B. amyloliquefaciens. The identification of a bacteriocin-like inhibitory A. Brandelli substance active against L. monocytogenes addresses an important aspect of food ICTA-UFRGS protection. [Int Microbiol 2006; 9(2):111-118] Av. Bento Gonçalves 9500 91501-970 Porto Alegre, Brazil Tel. +55-5133166249 Fax +55-5133167048 Key words: Bacillus amyloliquefaciens · antimicrobial activity · bacteriocin · E-mail: [email protected] bioactive peptide many attempts are being made to incorporate bacteriocins Introduction into processes and products [25].
    [Show full text]
  • Marmoset Models Commonly Used in Biomedical Research
    Comparative Medicine Vol 53, No 4 Copyright 2003 August 2003 by the American Association for Laboratory Animal Science Pages 383-392 Overview Marmoset Models Commonly Used in Biomedical Research Keith Mansfield, DVM The common marmoset (Callithrix jacchus ) is a small, nonendangered New World primate that is native to Brazil and has been used extensively in biomedical research. Historically the common marmoset has been used in neuro- science, reproductive biology, infectious disease, and behavioral research. Recently, the species has been used in- creasingly in drug development and safety assessment. Advantages relate to size, cost, husbandry, and biosafety issues as well as unique physiologic differences that may be used in model development. Availability and ease of breeding in captivity suggest that they may represent an alternative species to more traditional nonhuman pri- mates. The marmoset models commonly used in biomedical research are presented, with emphasis on those that may provide an alternative to traditional nonhuman primate species. In contrast to many other laboratory animal species, use of nonhuman primate species. nonhuman primates has increased in recent years and there Common marmosets represent an attractive alternative non- currently exists a substantial shortage of such animals for use human primate species for a variety of reasons. These small in biomedical research. The national supply of macaque mon- hardy animals breed well in captivity, with reproductive effi- keys has been unable to meet the current or projected demands ciency that may exceed 150% (number of live born per year/ of the research community. Although efforts are underway to number of breeding females). Furthermore, sexual maturity is increase domestic production and to identify alternative foreign reached by 18 months of age, allowing rapid expansion of exist- sources, this will unlikely alter short-term availability.
    [Show full text]
  • GRAS Notice 685, Lactobacillus Plantarum Strain 299V
    GRAS Notice (GRN) No. 685 http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm ORIGINAL SUBMISSION 1701 Pennsylvania Avenue, NW Attomeys at Law in Suite 700 Chicago Quoties/ Bmdy u.r Washington, District of Columbia 20006-5805 Indianapolis 202.372.9600 Madison Fax 202.372.9599 Milwaukee www.quarles.com Naples Phoenix Scottsdale Tampa Tucson Washington, D.C. Writer's Direct Dial: 202-372-9529 E-Mail: [email protected] December 20,2016 BY Hand Delivery United States Food and Drug Administration Center for Food Safety and Applied Nutrition Office ofFood Additive Safety HFS-200 5001 Campus Drive College Park, MD 20740 Re: GRAS Notification for Lactobacillus plantarum Strain 299v Dear Dr. Anderson: Enclosed is a copy of a GRAS notification submitted on behalfofProbi AB, of Lund, Sweden ("Probi") through its Agent Mark Yacura ofthe law firm Quarles & Brady LLP in accordance with the requirements of21 C.F.R. Part 170, Subpart E. If you have any questions or concerns regarding these minutes, please contact me at (202) 372-9529 or at [email protected]. Sincerely, (b) (6) fR1[E~[EG~[EfQJ DEC 2 1 2016 OFFICE OF FOOD ADDITIVE SAFETY Generally Recognized as Safe (GRAS) Determination for the Use of Lactobacillus plantarum Strain 299v in Conventional Foods Submitted by ProbiAB Lund, Sweden Submitted to United States Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Food Additive Safety HFS-200 5001 Campus Drive College Park, MD 20740 Prepared by ProbiAB and JHeimbach LLC Port Royal, Virginia December 2016 GRAS Determination for 1 JHEJMBACH LLC Lactobacillus plantarum 299v Table of Contents Part 1 - Signed Statements and Certification............................................................................
    [Show full text]
  • Non-Canonical Functions of the Bacterial Sos Response
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2019 Non-Canonical Functions Of The aB cterial Sos Response Amanda Samuels University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Microbiology Commons Recommended Citation Samuels, Amanda, "Non-Canonical Functions Of The aB cterial Sos Response" (2019). Publicly Accessible Penn Dissertations. 3253. https://repository.upenn.edu/edissertations/3253 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3253 For more information, please contact [email protected]. Non-Canonical Functions Of The aB cterial Sos Response Abstract DNA damage is a pervasive environmental threat, as such, most bacteria encode a network of genes called the SOS response that is poised to combat genotoxic stress. In the absence of DNA damage, the SOS response is repressed by LexA, a repressor-protease. In the presence of DNA damage, LexA undergoes a self-cleavage reaction relieving repression of SOS-controlled effector genes that promote bacterial survival. However, depending on the bacterial species, the SOS response has an expanded role beyond DNA repair, regulating genes involved in mutagenesis, virulence, persistence, and inter-species competition. Despite a plethora of research describing the significant consequences of the SOS response, it remains unknown what physiologic environments induce and require the SOS response for bacterial survival. In Chapter 2, we utilize a commensal E. coli strain, MP1, and established that the SOS response is critical for sustained colonization of the murine gut. Significantly, in evaluating the origin of the genotoxic stress, we found that the SOS response was nonessential for successful colonization in the absence of the endogenous gut microbiome, suggesting that competing microbes might be the source of genotoxic stress.
    [Show full text]
  • Bacteriocin Production by Newly Isolated Lactobacillus Strain
    IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS) e-ISSN:2278-3008, p-ISSN:2319-7676. Volume 11, Issue 3 Ver. I (May.- Jun.2016), PP 39-49 www.iosrjournals.org Bacteriocin Production by Newly Isolated Lactobacillus Strain Ahmed Abdelrazak1, Mahmoud M.Elaasser2,Manal Elshal1*, Haroun SA1 1Botany Department, Faculty of Science, Mansoura University, Egypt 2The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt Abstract: An Egyptian local Lactobacillus strain was isolated from Cabbage and was identified to be more closely related to thetypestrains LactobacilluspentosusD79211and LactobacillusarizonensisAJ965482via 16S rRNA gene sequencing and analysis. The isolated strain was found to be a gram positive, rods and react negatively with catalase test. A Central Composite Design [CCD] algorithm was applied to determine the optimum pH and incubation temperature required for the growth of L-CbM101. The fatty acids profile of the local isolate was explored using Gas Chromatography/ Mass Spectroscopy [GCMS] methodology revealing that the main fatty acids to be; oleicacid, palmitic acid, myristic acid and stearic acid. The isolated strain was found to be able to produce bacteriocin with antimicrobial activity against a vast number of pathogens and food spoiling microbes. The activity and stability of the produced bacteriocin was studied at different pH, storage time and temperature via applying a Response Surface Methodology and the optimum activity was achieved at pH 4, after 2 days of incubation and 4℃. These results indicate that; the produced bacteriocin could be used as antimicrobial compound added to fresh food taking the advantage from protect fresh food from spoilage and disappear of the antimicrobial compound prior to consumption which is undesirable.
    [Show full text]
  • Mechanisms and Consequences of Bacterial Resistance to Antimicrobial Peptides
    Drug Resistance Updates 26 (2016) 43–57 Contents lists available at ScienceDirect Drug Resistance Updates jo urnal homepage: www.elsevier.com/locate/drup Invited review Mechanisms and consequences of bacterial resistance to antimicrobial peptides ∗ D.I. Andersson , D. Hughes, J.Z. Kubicek-Sutherland Uppsala University, Department of Medical Biochemistry and Microbiology, Box 582, SE-751 23 Uppsala, Sweden a r t i c l e i n f o a b s t r a c t Article history: Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over Received 14 March 2016 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the Received in revised form 7 April 2016 increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an Accepted 11 April 2016 alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies Keywords: aimed at modulating the expression of AMPs to boost the human innate immune response. In this review Antimicrobial peptides we discuss the potential problems associated with these therapeutic approaches. There is considerable Anti-bacterial drugs Resistance experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population Innate immunity Selection of bacteria in a natural setting will be determined by a complex interplay of several different factors, Bacterial infections including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure.
    [Show full text]
  • The Antimicrobial Peptide, Nisin, Synergistically Enhances the Cytotoxic and Apoptotic Effects of Rituximab Treatment on Human Burkitt’S Lymphoma Cell Lines
    Reports of Biochemistry & Molecular Biology Vol.9, No.3, Oct 2020 Original article www.RBMB.net The Antimicrobial Peptide, Nisin, Synergistically Enhances the Cytotoxic and Apoptotic Effects of Rituximab Treatment on Human Burkitt’s Lymphoma Cell Lines Pantea Mohammadi1, Mina Zangeneh1, Hamid-Reza Mohammadi-Motlagh1, Fatemeh Khademi*1 Abstract Background: Non-Hodgkin’s lymphomas comprise the most common hematological cancers worldwide and consist of a heterogenous group of malignancies affecting the lymphoid system. Treatment of non-Hodgkin’s lymphoma has been significantly enhanced with the addition of Rituximab to the standard chemotherapy regimen. However, even with the advancement of treatment patients continue to relapse and develop resistance to Rituximab, rendering subsequent treatments unsuccessful. The use of novel drugs with unique antitumor mechanisms has gained considerable attention. In this study, we explored the in vitro anti-cancer effects of the combined therapy of Rituximab and Nisin on human Burkitt’s lymphoma cells. Methods: The human Burkitt’s lymphoma cells lines, Raji and Daudi, were treated with Nisin, Rituximab, or a combination of the two agents at various concentrations. Cytotoxicity following treatment was determined using cell viability assay. The degree of apoptosis was verified via flow cytometric analysis using FITC annexin V/PI staining. Results: Our findings show that the combined treatment of Rituximab and Nisin results in a more significant reduction in the survival of Raji and Daudi Burkitt’s lymphoma cells, compared to Nisin or Rituximab treatment alone. Additionally, our results indicate that Nisin can induce a significant degree of apoptosis in the Burkitt’s lymphoma cells compared to the negative controls.
    [Show full text]