DOCSLIB.ORG

Bacteroides Fragilis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bacteroides Fragilis FUNCTION AND REGULATION OF THE POLYSACCHARIDE UTILIZATION LOCUS, DON, IN THE GUT SYMBIONT BACTEROIDES FRAGILIS By Yanlu Cao August, 2014 Director of Dissertation: C. Jeffrey Smith, Ph.D. Major Department: Department of Microbiology and Immunology Abstract Bacteroides fragilis is the most common anaerobe isolated from clinical infections and in this report we demonstrate a novel feature of the species that is critical to their success as an opportunistic pathogen. Among the Bacteroides spp. in the gut, B. fragilis has a unique ability to efficiently harvest complex N-linked glycans from the glycoproteins common to serum and serous fluid. This activity is mediated by a Sus-like outer membrane protein complex designated as Don. Using the abundant serum glycoprotein transferrin as a model it was shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth and that this ability provides a competitive advantage in vivo over strains lacking the don locus. Thus, Don functionally is an extraintestinal growth factor that may contribute to B. fragilis opportunistic infection. The regulation of don expression is controlled by two independent pathways. The first one was shown to be a typical ECF sigma/anti-sigma factor switch, commonly found in Sus-like Polysaccharide Utilization Loci (PULs), which responds to the presence of specific substrate. In the ECF sigma factor deletion mutant, ΔdonA, expression of the don PUL was completely abolished in the presence of substrate glycans, while the cognate anti-sigma deletion strain, ΔdonB, expressed the don genes even in the absence of substrate glycans. The donA overexpressing strain highly expressed the don PUL regardless of the substrate glycan presence. The second regulatory pathway is involved with a cis-encoded antisense sRNA which is associated within the don locus, DonS. DonS was shown to negatively regulate don expression. In contrast, expression of the don genes was induced two- to six-fold in the donS silencing mutant and highly repressed in the donS overexpressing strain. Notably, this sRNA controlled regulatory pathway is not commonly found associated with B. fragilis PULs. Only 14 of more than 50 PULs in B. fragilis possess DonS-like sRNAs, but at the present time their roles in commensal colonization and opportunistic infections is not understood. FUNCTION AND REGULATION OF THE POLYSACCHARIDE UTILIZATION LOCUS, DON, IN THE GUT SYMBIONT BACTEROIDES FRAGILIS A Dissertation Presented to The Faculty of the Department of Microbiology and Immunology Brody School of Medicine at East Carolina University In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in Microbiology and Immunology By Yanlu Cao August 15th, 2014 ©Yanlu Cao, 2014 FUNCTION AND REGULATION OF THE POLYSACCHARIDE UTILIZATION LOCUS, DON, IN THE GUT SYMBIONT BACTEROIDES FRAGILIS by Yanlu Cao APPROVED BY: DIRECTOR OF DISSERTATION C. Jeffrey Smith, Ph.D. COMMITTEE MEMBER Everett C. Pesci, Ph.D. COMMITTEE MEMBER R. Martin Roop, II, Ph.D. COMMITTEE MEMBER Rachel L. Roper, Ph.D. COMMITTEE MEMBER Warren Knudson, Ph.D. CHAIR OF THE DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY C. Jeffrey Smith, Ph.D. INTERIM DEAN OF THE GRADUATED SCHOOL Paul J. Gemperline, Ph.D. ACKNOWLEDGEMENTS First I would like to thank my mother Hong Cao, who had encouraged and supported me to pursue an education and career in the United States, for her constant love. I would also like to thank all my family members from my maternal side, especially my grandparents, for their support and help since my childhood. For the past six years during my high education in ECU, I foremost have to give my thanks to my advisor, Dr. C. Jeffrey Smith. For his dedication and mentorship, I can accomplish the work in this study and be qualified to have a doctoral degree in microbiology and immunology. I also must thank Dr. Edson R. Rocha, Dr. Ivan Ndamukong, Anita C. Parker and Michael Betteken for their support and cooperation, both as co-workers and great friends. I also need to acknowledge Dr. Clayton C. Caswell for his technique support during the small RNA study. I would also like to thank my committee members, Dr. Everett C. Pesci, Dr. R. Martin Roop, II, Dr. Rachel L. Roper and Dr. Warren Knudson for their contribution to my educational development. For many years I always want, but have not had a chance, to say thanks to the Biology Department of Indiana University of Pennsylvania, especially to Dr. Carl Luciano and Dr. Narayanaswamy Bharathan, for their help which are not just limited to education. There are many people in my life that I sincerely appreciate but not be able to mention every one individually here. To them, I just want to say: thank you all and God bless. TABLE OF CONTENTS LIST OF TABLES .............................................................................................................................vi LIST OF FIGURES ...........................................................................................................................vii CHAPTER ONE: INTRODUCTION ...................................................................................................1 1.1 Bacteroides taxonomy, structure, physiology and metabolism ......................................1 1.2 The mutualistic relationship between Bacteroides and their hosts ................................7 1.3 Bacteroides as opportunistic pathogens .........................................................................10 1.4 Virulence Mechanisms .....................................................................................................11 1.5 The polysaccharide utilization systems in Bacteroides....................................................14 CHAPTER TWO: EFFICIENT UTILIZATION OF COMPLEX N-LINKED GLYCANS IS A SELECTIVE ADVANTAGE FOR BACTEROIDES FRAGILIS IN EXTRAINTESTINAL INFECTIONS ...........................21 2.1 Abstract ............................................................................................................................21 2.2 Significance ......................................................................................................................22 2.3 Introduction .....................................................................................................................22 2.4 Materials and methods ....................................................................................................24 2.4.1 Bacterial strains and growth .................................................................................24 2.4.2 Construction of a don operon deletion mutant ....................................................27 2.4.3 Animal model of infection .....................................................................................27 2.4.4 Total RNA extraction .............................................................................................28 2.4.5 cDNA synthesis, qRT-PCR, and microarray analysis ..............................................29 2.4.6 Whole cell deglycosylation assay ..........................................................................30 2.4.7 Glycomics analyses of B. fragilis treated human transferring ..............................30 2.5 Results ..............................................................................................................................31 2.5.1 In vivo, extraintestinal PUL expression .................................................................31 2.5.2 In vitro induction of the donCDEFG operon ..........................................................35 2.5.3 Deglycosylation of transferrin is mediated by donCDEFG ....................................38 2.5.4 Growth on transferrin as the sole carbon and energy source ..............................43 2.5.5 In vivo role of the don PUL ....................................................................................46 2.5.6 Efficient transferrin deglycosylation is unique to B. fragilis .................................50 2.6 Discussion.........................................................................................................................53 2.7 Supplementary Figures ....................................................................................................58 2.8 Addendum........................................................................................................................67 CHAPTER THREE: BACTEROIDES FRAGILIS PRIMARY TRANSCRIPTOME ANALYSIS ......................68 3.1 Introduction .....................................................................................................................68 3.2 Materials and Methods ....................................................................................................69 3.2.1 Total RNA Extraction .............................................................................................69 3.2.2 Preparation of cDNA libraries and 454 pyrosequencing ......................................69 3.2.3 Data Visualization ..................................................................................................70 3.3 Results ..............................................................................................................................71 3.3.1 Identification of B. fragilis TISs
Load more

Recommended publications
  • Characterisation of Streptococcus Pneumoniae Opacity Phase Variation
    Characterisation of Streptococcus pneumoniae Opacity Phase Variation Melissa Hui Chieh Chai, BBiomedSc (Hon), MSc A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy from the University of Adelaide February 2016 Research Centre for Infectious Diseases Department of Molecular and Cellular Biology The University of Adelaide Adelaide, S.A., Australia Table of Contents Chapter 1: INTRODUCTION ........................................................................... 1 1.1 The Pneumococcus ....................................................................................................... 1 1.1.1 Burden of Disease .................................................................................................. 1 1.1.2 Antimicrobial resistance ........................................................................................ 3 1.2 Pneumococcal Vaccines ............................................................................................... 4 1.3 Pathogenesis of Pneumococcal Disease ....................................................................... 7 1.3.1 Pneumococcal colonisation.................................................................................... 7 1.3.2 Progression to disease .......................................................................................... 10 1.4 S. pneumoniae Virulence Factors ............................................................................... 11 1.4.1 Pneumococcal capsule ........................................................................................
    [Show full text]
  • Mechanism of Nucleotide Flipping by Human Alkyladenine DNA Glycosylase
    Mechanism of Nucleotide Flipping by Human Alkyladenine DNA Glycosylase by Jenna M. Hendershot A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Biological Chemistry) in the University of Michigan 2014 Doctoral Committee: Associate Professor Patrick J. O’Brien, Chair Professor Hashim M. Al-Hashimi, Duke University Professor Carol A. Fierke Associate Professor Bruce A. Palfey Associate Professor Raymond C. Trievel © Jenna M. Hendershot 2014 Table of Contents List of Figures.………………….…………………………………………………………………………………………… iii List of Tables.……………………………………………………………………………………………………………….. vi List of Appendices.…….....…………………………………………………………………………………………….. vii List of Abbreviations..………………………………………………………………………………………………….. viii Abstract...…………………………………………………………………………………………………………………….. xi Chapter (1) Introduction…………………………………………………………………………………………………. 1 (2) Substitution of Active Site Tyrosines with Tryptophan Alters the Free Energy for Nucleotide Flipping by Human Alkyladenine DNA Glycosylase.………..……. 18 (3) Critical Role of DNA Intercalation in Enzyme-Catalyzed Nucleotide Flipping… 58 (4) Evidence for Early Intercalation during the Search for DNA Damage by Human Alkyladenine DNA Glycosylase………………………………..………………………. 94 (5) Structure/Function Analysis of Intercalation and Nucleotide Flipping in Human Alkyladenine DNA Glycosylase….…………………………………………………….. 124 (6) Conclusions and Future Directions……….………………………………………………………. 155 ii List of Figures Figure 1.1: Nucleotide flipping………………………………………………………………………………………
    [Show full text]
  • Characterization of the Relationship Between Measles Virus Fusion
    University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2006-05-17 Characterization of the Relationship Between Measles Virus Fusion, Receptor Binding, and the Virus-Specific Interaction Between the Hemagglutinin and Fusion Glycoproteins: a Dissertation Elizabeth Ann Corey University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Amino Acids, Peptides, and Proteins Commons, Cells Commons, Chemical Actions and Uses Commons, Lipids Commons, and the Virus Diseases Commons Repository Citation Corey EA. (2006). Characterization of the Relationship Between Measles Virus Fusion, Receptor Binding, and the Virus-Specific Interaction Between the Hemagglutinin and Fusion Glycoproteins: a Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/hg2y-0r35. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/221 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. CHARACTERIZATION OF THE RELATIONSHIP BETWEEN MEASLES VIRUS FUSION , RECEPTOR BINDING , AND THE VIRUS-SPECIFIC INTERACTION BETWEEN THE HEMAGGLUTININ AND FUSION GL YCOPROTEINS A Dissertation Presented Elizabeth Anne Corey Submitted to the Faculty of the University of Massachusetts Graduate
    [Show full text]
  • Assessing Lyme Disease Relevant Antibiotics Through Gut Bacteroides Panels
    Assessing Lyme Disease Relevant Antibiotics through Gut Bacteroides Panels by Sohum Sheth Abstract: Lyme borreliosis is the most prevalent vector-borne disease in the United States caused by the transmission of bacteria Borrelia burgdorferi harbored by the Ixodus scapularis ticks (Sharma, Brown, Matluck, Hu, & Lewis, 2015). Antibiotics currently used to treat Lyme disease include oral doxycycline, amoxicillin, and ce!riaxone. Although the current treatment is e"ective in most cases, there is need for the development of new antibiotics against Lyme disease, as the treatment does not work in 10-20% of the population for unknown reasons (X. Wu et al., 2018). Use of antibiotics in the treatment of various diseases such as Lyme disease is essential; however, the downside is the development of resistance and possibly deleterious e"ects on the human gut microbiota composition. Like other organs in the body, gut microbiota play an essential role in the health and disease state of the body (Ianiro, Tilg, & Gasbarrini, 2016). Of importance in the microbiome is the genus Bacteroides, which accounts for roughly one-third of gut microbiome composition (H. M. Wexler, 2007). $e purpose of this study is to investigate how antibiotics currently used for the treatment of Lyme disease in%uences the Bacteroides cultures in vitro and compare it with a new antibiotic (antibiotic X) identi&ed in the laboratory to be e"ective against B. burgdorferi. Using microdilution broth assay, minimum inhibitory concentration (MIC) was tested against nine di"erent strains of Bacteroides. Results showed that antibiotic X has a higher MIC against Bacteroides when compared to amoxicillin, ce!riaxone, and doxycycline, making it a promising new drug for further investigation and in vivo studies.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Letters to Nature
    letters to nature Received 7 July; accepted 21 September 1998. 26. Tronrud, D. E. Conjugate-direction minimization: an improved method for the re®nement of macromolecules. Acta Crystallogr. A 48, 912±916 (1992). 1. Dalbey, R. E., Lively, M. O., Bron, S. & van Dijl, J. M. The chemistry and enzymology of the type 1 27. Wolfe, P. B., Wickner, W. & Goodman, J. M. Sequence of the leader peptidase gene of Escherichia coli signal peptidases. Protein Sci. 6, 1129±1138 (1997). and the orientation of leader peptidase in the bacterial envelope. J. Biol. Chem. 258, 12073±12080 2. Kuo, D. W. et al. Escherichia coli leader peptidase: production of an active form lacking a requirement (1983). for detergent and development of peptide substrates. Arch. Biochem. Biophys. 303, 274±280 (1993). 28. Kraulis, P.G. Molscript: a program to produce both detailed and schematic plots of protein structures. 3. Tschantz, W. R. et al. Characterization of a soluble, catalytically active form of Escherichia coli leader J. Appl. Crystallogr. 24, 946±950 (1991). peptidase: requirement of detergent or phospholipid for optimal activity. Biochemistry 34, 3935±3941 29. Nicholls, A., Sharp, K. A. & Honig, B. Protein folding and association: insights from the interfacial and (1995). the thermodynamic properties of hydrocarbons. Proteins Struct. Funct. Genet. 11, 281±296 (1991). 4. Allsop, A. E. et al.inAnti-Infectives, Recent Advances in Chemistry and Structure-Activity Relationships 30. Meritt, E. A. & Bacon, D. J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277, 505± (eds Bently, P. H. & O'Hanlon, P. J.) 61±72 (R. Soc. Chem., Cambridge, 1997).
    [Show full text]
  • The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z
    REVIEW pubs.acs.org/CR The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z. Long* and Benjamin F. Cravatt* The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States CONTENTS 2.4. Other Phospholipases 6034 1. Introduction 6023 2.4.1. LIPG (Endothelial Lipase) 6034 2. Small-Molecule Hydrolases 6023 2.4.2. PLA1A (Phosphatidylserine-Specific 2.1. Intracellular Neutral Lipases 6023 PLA1) 6035 2.1.1. LIPE (Hormone-Sensitive Lipase) 6024 2.4.3. LIPH and LIPI (Phosphatidic Acid-Specific 2.1.2. PNPLA2 (Adipose Triglyceride Lipase) 6024 PLA1R and β) 6035 2.1.3. MGLL (Monoacylglycerol Lipase) 6025 2.4.4. PLB1 (Phospholipase B) 6035 2.1.4. DAGLA and DAGLB (Diacylglycerol Lipase 2.4.5. DDHD1 and DDHD2 (DDHD Domain R and β) 6026 Containing 1 and 2) 6035 2.1.5. CES3 (Carboxylesterase 3) 6026 2.4.6. ABHD4 (Alpha/Beta Hydrolase Domain 2.1.6. AADACL1 (Arylacetamide Deacetylase-like 1) 6026 Containing 4) 6036 2.1.7. ABHD6 (Alpha/Beta Hydrolase Domain 2.5. Small-Molecule Amidases 6036 Containing 6) 6027 2.5.1. FAAH and FAAH2 (Fatty Acid Amide 2.1.8. ABHD12 (Alpha/Beta Hydrolase Domain Hydrolase and FAAH2) 6036 Containing 12) 6027 2.5.2. AFMID (Arylformamidase) 6037 2.2. Extracellular Neutral Lipases 6027 2.6. Acyl-CoA Hydrolases 6037 2.2.1. PNLIP (Pancreatic Lipase) 6028 2.6.1. FASN (Fatty Acid Synthase) 6037 2.2.2. PNLIPRP1 and PNLIPR2 (Pancreatic 2.6.2.
    [Show full text]
  • Effects of a Low-Fat Vegan Diet on Gut Microbiota in Overweight
    nutrients Article Effects of a Low-Fat Vegan Diet on Gut Microbiota in Overweight Individuals and Relationships with Body Weight, Body Composition, and Insulin Sensitivity. A Randomized Clinical Trial Hana Kahleova 1,*, Emilie Rembert 1, Jihad Alwarith 1, Willy N. Yonas 1, Andrea Tura 2, Richard Holubkov 3, Melissa Agnello 4, Robynne Chutkan 5 and Neal D. Barnard 1,6 1 Physicians Committee for Responsible Medicine, Washington, DC 20016, USA; [email protected] (E.R.); [email protected] (J.A.); [email protected] (W.N.Y.); [email protected] (N.D.B.) 2 Metabolic Unit, CNR Institute of Neuroscience, 35127 Padua, Italy; [email protected] 3 School of Medicine, University of Utah, Salt Lake City, UT 84132, USA; [email protected] 4 uBiome Inc., San Francisco, CA 94103, USA; [email protected] 5 Department of Gastroenterology, Georgetown MedStar Hospital, Washington, DC 20007, USA; [email protected] 6 Adjunct Faculty, George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA * Correspondence: [email protected]; Tel.: +1-202-527-7379 Received: 24 August 2020; Accepted: 20 September 2020; Published: 24 September 2020 Abstract: Diet modulates gut microbiota and plays an important role in human health. The aim of this study was to test the effect of a low-fat vegan diet on gut microbiota and its association with weight, body composition, and insulin resistance in overweight men and women. We enrolled 168 participants and randomly assigned them to a vegan (n = 84) or a control group (n = 84) for 16 weeks. Of these, 115 returned all gut microbiome samples.
    [Show full text]
  • Bacteroides Gingivalis, and Bacteroides Endodontalis in a New Genus, Porphyromonas H
    INTERNATIONALJOURNAL OF SYSTEMATICBACTERIOLOGY, Jan. 1988, p. 128-131 Vol. 38, No. 1 0020-7713/88/010128-04$02.00/0 Copyright 0 1988, International Union of Microbiological Societies Proposal for Reclassification of Bacteroides asaccharolyticus , Bacteroides gingivalis, and Bacteroides endodontalis in a New Genus, Porphyromonas H. N. SHAH1* AND M. D. COLLINS’ Department of Oral Microbiology, London Hospital Medical College, London El 2AD,l and Division of Microbiology, AFRC Institute of Food Research, Shinfeld, Reading RG2 9AT,= United Kingdom The asaccharolytic, pigmented Bacteroides, Bacteroides asaccharolyticus, Bacteroides gingivalis, and Bacte- roides endodontalis, form a group of relatively homogeneous species which differ markedly in biochemical and chemical properties from the type species of Bacteroides, Bacteroides fragilis (Castellani and Chalmers), such that they should not be retained within this genus. Therefore, we propose that Bacteroides asaccharolyticus (Holdeman and Moore) Finegold and Barnes, Bacteroides gingivalis Coykendhll, Kaczmarek and Slots, and Bacteroides endodontalis van Steenbergen, van Winkelhoff, Mayrand, Grenier and de Graaff be reclassified in a new genus, Porphyromonas, as Porphyromonas asaccharolytica comb. nov., Porphyromonas gingivalis comb. nov., and Porphyromonas endodontalis comb. nov., respectively. In Bergey ’s Manual of Determinative Bacteriology, 8th quite unrelated to the type species of the genus Bacteroides, ed. (12), the asaccharolytic, pigmented Bacteroides were Bacteroides fragilis. All of the asaccharolytic, pigmented regarded as a single homogeneous taxon, Bacteroides mela- bacteroides accumulate major levels of protoheme rather ninogenicus subsp. asaccharolyticus. As the clinical signif- than protoporphyrin when cells are cultured on blood agar icance of these microorganisms in oral cavities was recog- (3,25, 27). The three species are nonfermentative and utilize nized, extensive taxonomic studies were carried out.
    [Show full text]
  • Thesis Rests with Its Author
    University of Bath PHD An investigation of platelet-activating factor metabolism during normal and pre- eclamptic pregnancies Khan, Nighat Murad Award date: 1993 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 10. Oct. 2021 (i) A r c INVESTIGATION OF A 3sr o R METABOLISM DURING NORMAL AND PRE-ECLAMPTIC PREGNANCIES. Submitted by Nighat Murad Khan for the degree of Ph.D of the University of Bath 1992 Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on the condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without written consent of the author.
    [Show full text]
  • Non-Sporing Anaerobes
    NON-SPORING ANAEROBES Dr. R.K.Kalyan Professor Microbiology KGMU, Lko Beneficial Role of Commensal non-sporing Anaerobes Part of normal flora, modulate physiological functions Compete with pathogenic bacteria Modulate host’s intestinal innate immune response‰ Production of vitamins like biotin, vit-B12 and K ‰Polysaccharide A of Bacteroides fragilis influences the normal development and function of immune system and protects against inflammatory bowel disease. Lactobacilli maintain the vaginal acidic pH which prevents colonization of pathogens. Non-sporing Anaerobes Causing Disease ‰Anaerobic infections occur when the harmonious relationship between the host and the bacteria is disrupted ‰Disruption of anatomical barrier (skin and mucosal barrier) by surgery, trauma, tumour, ischemia, or necrosis (all of which can reduce local tissue redox potentials) allow the penetration of many anaerobes, resulting in mixed infection Classification of non-sporing anaerobes Gram-positive cocci Gram-negative cocci • Peptostreptococcus •Veillonella • Peptococcus Gram-positive bacilli Gram-negative bacilli •Bifidobacterium • Bacteroides • Eubacterium • Prevotella • Propionibacterium • Porphyromonas • Lactobacillus • Fusobacterium •Actinomyces • Leptotrichia • Mobiluncus Spirochete • Treponema, Borrelia Anaerobes as a part of normal flora Anatomic Total Anaerobic/Aero Common anaerobic al Site bacteria/ bic Ratio Normal flora gm or ml MOUTH Saliva 108–109 1:1 Anaerobic cocci Actinomyces 10 11 Tooth 10 –10 1:1 Fusobacterium surface Bifidobacterium
    [Show full text]
  • 3-Methyladenine DNA Glycosylases: Structure, Function, and Biological Importance Michael D
    Review articles 3-Methyladenine DNA glycosylases: structure, function, and biological importance Michael D. Wyatt,1 James M. Allan,1 Albert Y. Lau,2 Tom E. Ellenberger,2 and Leona D. Samson1* Summary The genome continuously suffers damage due to its reactivity with chemical and physical agents. Finding such damage in genomes (that can be several million to several billion nucleotide base pairs in size) is a seemingly daunting task. 3-Methyladenine DNA glycosylases can initiate the base excision repair (BER) of an extraordinarily wide range of substrate bases. The advantage of such broad substrate recognition is that these enzymes provide resistance to a wide variety of DNA damaging agents; however, under certain circumstances, the eclectic nature of these enzymes can confer some biological disadvantages. Solving the X-ray crystal struc- tures of two 3-methyladenine DNA glycosylases, and creating cells and animals altered for this activity, contributes to our understanding of their enzyme mechanism and how such enzymes influence the biological response of organisms to several different types of DNA damage. BioEssays 21:668–676, 1999. ௠ 1999 John Wiley & Sons, Inc. Introduction ately interpreted by DNA-processing enzymes. Unfortunately, DNA carries life’s genetic information encoded in the arrange- these bases are also chemically reactive, and the inevitable ment of bases along the length of the DNA molecule. Each base modifications produce a variety of biological outcomes, DNA base has a distinct chemical structure that is appropri- depending on how a cell recognizes and responds to the modification. Cellular DNA repair mechanisms target these inappropriate DNA structures, and play a vital role in maintain- 1Department of Cancer Cell Biology, Harvard School of Public Health, ing genomic integrity.
    [Show full text]