DOCSLIB.ORG

Natural Strategies for Controlling Virulence and Antibiotic Resistance

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

University of Connecticut OpenCommons@UConn Doctoral Dissertations University of Connecticut Graduate School 1-14-2019 Natural Strategies for Controlling Virulence and Antibiotic Resistance in Clostridium difficile Abraham Joseph Pellissery University of Connecticut - Storrs, [email protected] Follow this and additional works at: https://opencommons.uconn.edu/dissertations Recommended Citation Pellissery, Abraham Joseph, "Natural Strategies for Controlling Virulence and Antibiotic Resistance in Clostridium difficile" (2019). Doctoral Dissertations. 2036. https://opencommons.uconn.edu/dissertations/2036 Natural Strategies for Controlling Virulence and Antibiotic Resistance in Clostridium difficile Abraham Joseph Pellissery, PhD University of Connecticut, 2019 Clostridium difficile is a significant enteric pathogen causing a toxin-mediated infection and diarrhea in humans. There has been an increased incidence of C. difficile infection (CDI) in the United States with the emergence of hypervirulent strains and community associated outbreaks. CDI is commonly observed among hospital in-patients undergoing protracted antibiotic therapy, which results in gastrointestinal dysbiosis, creating a conducive environment for spore germination, pathogen colonization in the gut, and subsequent toxin production. An ideal anti- C.difficile therapeutic agent should inhibit critical virulence factors of the pathogen such as toxin production, sporulation and spore germination without inducing gut dysbiosis. Such agents when provided as an adjunct to C. difficile antibiotic therapy could help to improve the clinical outcome of CDI and prevent the relapse of the infection. In this Ph.D. research, the efficacy of three alternative treatment approaches as antivirulence agents was tested for potential future development as therapies against CDI. This included sodium selenite (metalloid), baicalin (flavone glycoside), and selected lactic acid bacteria. All treatment modalities were tested for inhibiting toxin production, sporulation and spore outgrowth in two hypervirulent C. difficile isolates. Moreover, gene expression and cell culture studies were performed to elucidate the anti-toxigenic mechanism of sodium selenite and baicalin. In addition, the effect of sodium selenite in increasing pathogen sensitivity to ciprofloxacin and vancomycin, two common antibiotics used in treating C. difficile, was also tested. Furthermore, the effect of baicalin on CDI was investigated in a mouse model, with special reference to its effect on disease severity and the mouse gut microbiome. The Abraham Joseph Pellissery – University of Connecticut, 2019 results revealed that sub-minimum inhibitory concentration (sub-MIC) and sub-inhibitory concentrations (SIC) of sodium selenite and baicalin, respectively, reduced C. difficile toxin production and cytotoxicity in vitro. In addition, sodium selenite and baicalin inhibited spore outgrowth. Oral supplementation of baicalin improved the clinical outcome in challenged mice, and positively altered the gut microbiome composition. Collectively, these results indicate that the three approaches identified in this study significantly reduced C. difficile virulence, however, follow up validation in animal models for long-term safety and dose standardization, and clinical trials in human subjects are necessary. Natural Strategies for Controlling Virulence and Antibiotic Resistance in Clostridium difficile Abraham Joseph Pellissery B.V.Sc. & A.H., Kerala Agricultural University, 2006 M.V.Sc. Indian Veterinary Research Institute, 2009 A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy at the University of Connecticut 2019 Copyright by Abraham Joseph Pellissery 2019 ii APPROVAL PAGE Doctor of Philosophy Dissertation Natural Strategies for Controlling Virulence and Antibiotic Resistance in Clostridium difficile Presented by Abraham Joseph Pellissery, B.V.Sc. & A.H., M.V.Sc. Major Advisor……………………………………………………………….. Dr. Kumar Venkitanarayanan Associate Advisor………………………………………………………………. Dr. Mary Anne Roshni Amalaradjou Associate Advisor………………………………………………………………. Dr. Dennis J. D’Amico Associate Advisor………………………………………………………………. Dr. Mazhar I. Khan Associate Advisor………………………………………………………………. Dr. Bhushan M. Jayarao University of Connecticut 2019 iii ACKNOWLEDGEMENTS I would like to express my gratitude and immense respect to my major advisor, Dr. Kumar Venkitanarayanan, for his continual guidance and support throughout my tenure as a graduate student. I consider myself so blessed and privileged to have got the opportunity to work under the able tutelage of such an enthusiastic and hard-working researcher. The experiences that I gained from his lab helped me to evolve as an independent researcher and a critical theorist in the microbial sciences. I would like to express my sincere gratitude to my associate advisors, Dr. Mary Anne Amalaradjou, Dr. Dennis D’Amico, Dr. Mazhar Khan and Dr. Bhushan Jayarao for their continuous encouragement, critical advice and suggestions throughout my doctoral research. I would also like to extend my gratitude to all the Faculty, graduate students and administrative staff of the UConn Animal Science department for all the help and support provided to me during my life here as a doctoral student. My sincerest and profound gratitude to my dear friends: Ajith, Shafeekh, Sambhu, Shaan, Bindu, Elza, Deepa and Poonam for your camaraderie during the sunny and rainy days of my student life at UConn. Words are not enough to express my gratitude to my mother, Mrs. Mary Joseph and my parents-in-law, Mr. Anto E.V. and Mrs. Lissy Varghese for their unfailing support and prayers when I needed it the most. I remember and thank my father, Late Mr. P. C. Joseph for all the love, care, support and blessings that he has provided me I am sure that my father would be proud of me on my achievement up in heaven. I am grateful to my siblings James and Teresa, my in-laws Tina, Annlyn, Manu, Sharon and Arun, and my nieces and nephew, Sarah, Rahael and Gabriel: for all their heartwarming kindness and support. iv I would like to express my deepest love and thanks to my daughters Annarita and Helenna for their laughter, naughtiness, kisses and hugs that magically made my rough days much better. I also want to thank my wife Liya, for her wonderful companionship, understanding, patience and love throughout the last eight years. Lastly, I thank the Almighty for strengthening me to successfully complete my endeavor as a doctoral student and for all the blessings showered upon me throughout my life. v TABLE OF CONTENTS Approval page…………………………………………………………………………... iii Acknowledgments…………………………..………………………………………..... iv Table of Contents……………………………………………………………………….. vi List of figures…………………………………………………………………………… xii List of tables……………………………………………………………………………. xv List of abbreviations……………………………………………………………………. xvi Chapter I: Introduction………………………………………………………………. 1 Chapter II: Review of literature……………………………………………………… 7 1. Clostridium difficile or Clostridioides difficile (CD)…………………………....……… 8 1.1.Epidemiology of CDI…………………………………...………………………………… 10 1.2.Clinical manifestations and risk factors associated with CDI in humans…..…….. 14 1.3.Pathogenesis of CDI………………………………..…………………………..………... 15 1.4.C. difficile toxins…………………………………………………………………….……. 17 1.5. Non-toxin associated virulence factors initiating host colonization..…………… 20 1.6. C. difficile sporulation ………………………………………………………………… 21 1.7. C. difficile spore germination………….……………………………………………… 23 1.8. Influence of gut microbiome on CDI susceptibility.………………………………… 24 2. Antimicrobial resistance in C. difficile…..……………………………………………… 26 3. Treatment approaches for human CDI…………………………………………………… 27 3.1. Current and novel antimicrobials for CDI…….…………………………….….. 29 3.2. Alternate and emerging treatment strategies for CDI..……………………………. 29 3.2.1. Immunization strategies…………………………………………………………... 29 vi 3.2.2. Fecal microbiota transplantation……………………………………………….. 30 3.2.3. Non-toxigenic strains of C. difficile……………………………………………... 30 3.2.4. Emerging strategies for CDI therapy….………………………………………… 31 4. Metals 32 5. Phytochemicals 34 6. Probiotic therapy 36 References………………………………………………………………………………………… 39 Chapter III: In vitro efficacy of sodium selenite on toxin production, spore outgrowth and antibiotic resistance in hypervirulent Clostridium difficile….…….. 60 Abstract…………………………………………………………………………………. 61 1. Introduction…………………………………………………………………………... 62 2. Materials and Methods……………………………………………………………….. 63 2.1. Bacterial isolates and culture conditions……..……………………………………... 63 2.2. Establishment of sub-minimum inhibitory concentration and minimum inhibitory concentration of sodium selenite and antibiotics ………………………………. 64 2.3. Effect of sodium selenite on C. difficile Toxin Production and Cytotoxicity…… 65 2.4. ELISA for Total Toxin A and B……………………………………………………….. 65 2.5. Cytotoxicity Assay………………………………………………………………………. 66 2.6. Real-Time Quantitative PCR (RT-qPCR)….………………………………………… 66 2.7. Effect of sodium selenite on C. difficile spore germination and outgrowth….….. 67 2.8. Effect of sodium selenite on antibiotic resistance in C. difficile….………………. 68 2.9. Statistical analysis…..………………………………………………………………….. 68 3. Results………………………………….………………………………………………….. 68 vii 3.1. Sub-minimum inhibitory concentrations and minimum inhibitory concentrations of sodium selenite and antibiotics…………………………...……………… 68 3.2. Effect of selenium on C. difficile toxin production……………………………………
Recommended publications
  • Invasive Group a Streptococcal Disease Communicable Disease Control Unit

    Invasive Group a Streptococcal Disease Communicable Disease Control Unit

    Public Health and Primary Health Care Communicable Disease Control 4th Floor, 300 Carlton St, Winnipeg, MB R3B 3M9 T 204 788-6737 F 204 948-2040 www.manitoba.ca November, 2015 Re: Streptococcal Invasive Disease (Group A) Reporting and Case Investigation Reporting of Streptococcal invasive disease (Group A) (Streptococcus pyogenes) is as follows: Laboratory: All specimens isolated from sterile sites (refer to list below) that are positive for S. pyogenes are reportable to the Public Health Surveillance Unit by secure fax (204-948-3044). Health Care Professional: Probable (clinical) cases of Streptococcal invasive disease (Group A) are reportable to the Public Health Surveillance Unit using the Clinical Notification of Reportable Diseases and Conditions form (http://www.gov.mb.ca/health/publichealth/cdc/protocol/form13.pdf) ONLY if a positive lab result is not anticipated (e.g., poor or no specimen taken, person has recovered). Cooperation in Public Health investigation (when required) is appreciated. Regional Public Health or First Nations Inuit Health Branch (FNIHB): Cases will be referred to Regional Public Health or FNIHB. Completion and return of the Communicable Disease Control Investigation Form is generally not required, unless otherwise directed by a Medical Officer of Health. Sincerely, “Original Signed By” “Original Signed By” Richard Baydack, PhD Carla Ens, PhD Director, Communicable Disease Control Director, Epidemiology & Surveillance Public Health and Primary Health Care Public Health and Primary Health Care Manitoba Health, Healthy Living and Seniors Manitoba Health, Healthy Living and Seniors The sterile and non-sterile sites listed below represent commonly sampled body sites for the purposes of diagnosis, but the list is not exhaustive.
  • Toxic Shock-Like Syndrome Associated with Necrotizing Streptococcus Pyogenes Infection

    Toxic Shock-Like Syndrome Associated with Necrotizing Streptococcus Pyogenes Infection

    Henry Ford Hospital Medical Journal Volume 37 Number 2 Article 5 6-1989 Toxic Shock-like Syndrome Associated with Necrotizing Streptococcus Pyogenes Infection Thomas J. Connolly Donald J. Pavelka Eugene F. Lanspa Thomas L. Connolly Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Connolly, Thomas J.; Pavelka, Donald J.; Lanspa, Eugene F.; and Connolly, Thomas L. (1989) "Toxic Shock- like Syndrome Associated with Necrotizing Streptococcus Pyogenes Infection," Henry Ford Hospital Medical Journal : Vol. 37 : No. 2 , 69-72. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol37/iss2/5 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Toxic Shock-like Syndrome Associated with Necrotizing Streptococcus Pyogenes Infection Thomas J. Connolly,* Donald J. Pavelka, MD,^ Eugene F. Lanspa, MD, and Thomas L. Connolly, MD' Two patients with toxic shock-like syndrome are presented. Bolh patients had necrotizing cellulitis due to Streptococcus pyogenes, and both patients required extensive surgical debridement. The association of Streptococcus pyogenes infection and toxic shock-like syndrome is discussed. (Henry Ford Hosp MedJ 1989:37:69-72) ince 1978, toxin-producing strains of Staphylococcus brought to the emergency room where a physical examination revealed S aureus have been implicated as the cause of the toxic shock a temperature of 40.9°C (I05.6°F), blood pressure of 98/72 mm Hg, syndrome (TSS), which is characterized by fever and rash and respiration of 36 breaths/min, and a pulse of 72 beats/min.
  • ( 12 ) United States Patent

    ( 12 ) United States Patent

    US010231994B2 (12 ) United States Patent (10 ) Patent No. : US 10 , 231, 994 B2 Kuklinski et al. (45 ) Date of Patent: Mar. 19 , 2019 ( 54 ) SELENIUM -CONTAINING COMPOSITIONS 5 ,470 , 880 A 11 / 1995 Yu et al. 5 ,512 , 200 A 4 / 1996 Garcia AND USES THEREOF 5 , 536 ,497 A 7 / 1996 Evans et al . 6 , 069 , 152 A 5 / 2000 Schaus et al. (71 ) Applicant : SELO MEDICAL GMBH , Unternberg 6 , 114 , 348 A 9 / 2000 Weber et al. (AT ) 6 , 120 ,758 A 9 / 2000 Siddiqui et al . 6 , 133 , 237 A 10 / 2000 Noll et al. 6 , 277 , 835 B1 8 / 2001 Brown (72 ) Inventors : Bodo Kuklinski, Rostock (DE ) ; Peter 6 , 391 , 323 B1 5 / 2002 Carnevali Kössler , Mariapfarr ( AT ); Norbert 2003 / 0180387 AL 9 / 2003 Kossler et al . Fuchs , Mariapfarr (AT ) 2004 /0265268 A1 * 12 /2004 Jain . A61K 8 /64 424 /85 . 1 (73 ) Assignee : SELO MEDICAL GMBH , Unternberg 2005 /0048134 AL 3 /2005 Kuklinski et al. ( AT ) FOREIGN PATENT DOCUMENTS ( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 DE 3408362 9 / 1984 DE 43 20 694 1 / 1995 U . S . C . 154 (b ) by 0 days . DE 43 35 441 4 / 1995 DE 44 13 839 10 / 1995 (21 ) Appl. No. : 15 / 725 , 455 EP 0 000 670 2 / 1979 EP 0 750 911 1 / 1997 ( 22 ) Filed : Oct. 5 , 2017 EP 0 913 155 5 / 1999 FR 2 779 720 12 / 1999 GB 2323030 9 / 1998 (65 ) Prior Publication Data WO WO 00 / 12101 3 /2000 US 2018 / 0028559 A1 Feb .
  • VENEREAL DISEASES in ETHIOPIA Survey and Recommendations THORSTEIN GUTHE, M.D., M.P.H

    VENEREAL DISEASES in ETHIOPIA Survey and Recommendations THORSTEIN GUTHE, M.D., M.P.H

    Bull. World Hlth Org. 1949, 2, 85-137 10 VENEREAL DISEASES IN ETHIOPIA Survey and Recommendations THORSTEIN GUTHE, M.D., M.P.H. Section on Venereal Diseases World Health Organization Page 1. Prevalent diseases . 87 1.1 Historical .............. 87 1.2 Distribution.............. 88 2. Syphilis and related infections . 89 2.1 Spread factors . 89 2.2 Nature of syphilis . 91 2.3 Extent of syphilis problem . 98 2.4 Other considerations . 110 3. Treatment methods and medicaments . 114 3.1 Ancient methods of treatment . 114 3.2 Therapy and drugs . 115 4. Public-health organization. 116 4.1 Hospital facilities . 117 4.2 Laboratory facilities . 120 4.3 Personnel .............. 121 4.4 Organizational structure . 122 4.5 Legislation.............. 124 5. Recommendations for a venereal-disease programme . 124 5.1 General measures. ........... 125 5.2 Personnel, organization and administration . 126 5.3 Collection of data . 127 5.4 Diagnostic and laboratory facilities . 129 5.5 Treatment facilities . 130 5.6 Case-finding, treatment and follow-up . 131 5.7 Budget. ......... ... 134 6. Summary and conclusions . 134 References . 136 In spite of considerable handicaps, valuable developments in health took place in Ethiopia during the last two decades. This work was abruptly arrested by the war, and the fresh start necessary on the liberation of the country emphasized that much health work still remains to be done. A realistic approach to certain disease-problems and the necessity for compe- tent outside assistance to tackle such problems form the basis for future work. The accomplishments of the Ethiopian Government in the limited time since the war bode well for the future.
  • Current Trends of Enterococci in Dairy Products: a Comprehensive Review of Their Multiple Roles

    Current Trends of Enterococci in Dairy Products: a Comprehensive Review of Their Multiple Roles

    foods Review Current Trends of Enterococci in Dairy Products: A Comprehensive Review of Their Multiple Roles Maria de Lurdes Enes Dapkevicius 1,2,* , Bruna Sgardioli 1,2 , Sandra P. A. Câmara 1,2, Patrícia Poeta 3,4 and Francisco Xavier Malcata 5,6,* 1 Faculty of Agricultural and Environmental Sciences, University of the Azores, 9700-042 Angra do Heroísmo, Portugal; [email protected] (B.S.); [email protected] (S.P.A.C.) 2 Institute of Agricultural and Environmental Research and Technology (IITAA), University of the Azores, 9700-042 Angra do Heroísmo, Portugal 3 Microbiology and Antibiotic Resistance Team (MicroART), Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal; [email protected] 4 Associated Laboratory for Green Chemistry (LAQV-REQUIMTE), University NOVA of Lisboa, 2829-516 Lisboa, Portugal 5 LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 420-465 Porto, Portugal 6 FEUP—Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal * Correspondence: [email protected] (M.d.L.E.D.); [email protected] (F.X.M.) Abstract: As a genus that has evolved for resistance against adverse environmental factors and that readily exchanges genetic elements, enterococci are well adapted to the cheese environment and may reach high numbers in artisanal cheeses. Their metabolites impact cheese flavor, texture, Citation: Dapkevicius, M.d.L.E.; and rheological properties, thus contributing to the development of its typical sensorial properties. Sgardioli, B.; Câmara, S.P.A.; Poeta, P.; Due to their antimicrobial activity, enterococci modulate the cheese microbiota, stimulate autoly- Malcata, F.X.
  • Oral Administration of Lactobacillus Gasseri SBT2055 Is Effective In

    Oral Administration of Lactobacillus Gasseri SBT2055 Is Effective In

    www.nature.com/scientificreports OPEN Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas Received: 23 June 2015 Accepted: 7 March 2017 gingivalis-accelerated periodontal Published: xx xx xxxx disease R. Kobayashi1, T. Kobayashi2, F. Sakai3, T. Hosoya3, M. Yamamoto1 & T. Kurita-Ochiai1 Probiotics have been used to treat gastrointestinal disorders. However, the effect of orally intubated probiotics on oral disease remains unclear. We assessed the potential of oral administration of Lactobacillus gasseri SBT2055 (LG2055) for Porphyromonas gingivalis infection. LG2055 treatment significantly reduced alveolar bone loss, detachment and disorganization of the periodontal ligament, and bacterial colonization by subsequent P. gingivalis challenge. Furthermore, the expression and secretion of TNF-α and IL-6 in gingival tissue was significantly decreased in LG2055-administered mice after bacterial infection. Conversely, mouse β-defensin-14 (mBD-14) mRNA and its peptide products were significantly increased in distant mucosal components as well as the intestinal tract to which LG2055 was introduced. Moreover, IL-1β and TNF-α production from THP-1 monocytes stimulated with P. gingivalis antigen was significantly reduced by the addition of humanβ -defensin-3. These results suggest that gastrically administered LG2055 can enhance immunoregulation followed by periodontitis prevention in oral mucosa via the gut immune system; i.e., the possibility of homing in innate immunity. Porphyromonas gingivalis, a Gram-negative anaerobe, is one of the major pathogens associated with chronic periodontitis, a disease that causes the destruction of alveolar bone, and, as a consequence, tooth loss1. Recent evidence suggests that this bacterium contributes to periodontitis by functioning as a keystone pathogen2, 3.
  • Analyzing the Early Stages of Clostridium Difficile Spore

    Analyzing the Early Stages of Clostridium Difficile Spore

    ANALYZING THE EARLY STAGES OF CLOSTRIDIUM DIFFICILE SPORE GERMINATION A Dissertation by MICHAEL FRANCIS Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Chair of Committee, Joseph A. Sorg Committee Members, James L. Smith Matthew S. Sachs Paul D. Straight Head of Department, Thomas D. McKnight May 2017 Major Subject: Microbiology Copyright 2017 Michael Francis ABSTRACT Infections caused by Clostridium difficile have increased steadily over the past several years. While studies on C. difficile virulence and physiology have been hindered, in the past, by lack of genetic approaches and suitable animal models, newly developed technologies and animal models allow for improved experimental detail. One such advance was the generation of a mouse-model of C. difficile infection. This system was an important step forward in the analysis of the genetic requirements for colonization and infection. Equally important is understanding the differences that exist between mice and humans. One of these differences is the natural bile acid composition. Bile acid-mediated spore germination, a process whereby a dormant spore returns to active, vegetative growth, is an important step during C. difficile colonization. Mice produce several different bile acids that are not found in humans (muricholic acids) that have the potential to impact C. difficile spore germination. In order to understand potential effects of these different bile acids on C. difficile physiology, we characterized their effects on C. difficile spore germination and growth of vegetative cells. We found that the mouse-derived muricholic acids affect germination similarly to a previously-described inhibitor of germination, chenodeoxycholic acid.
  • Bacteriocin‐Like Inhibitory Activities of Seven Lactobacillus Delbrueckii

    Bacteriocin‐Like Inhibitory Activities of Seven Lactobacillus Delbrueckii

    Letters in Applied Microbiology ISSN 0266-8254 ORIGINAL ARTICLE Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains L. Boyanova, G. Gergova, R. Markovska, D. Yordanov and I. Mitov Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria Significance and Impact of the Study: In this study, anti-Helicobacter pylori activity of seven Lactobacil- lus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. Keywords Abstract antibiotics, bacteriocins, Helicobacter, Lactobacillus, probiotics. The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free Correspondence supernatant (CFS) types. Activity of non-neutralized and non-heat-treated Lyudmila Boyanova, Department of Medical (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase- Microbiology, Medical University of Sofia, treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated Zdrave Street 2, 1431 Sofia, Bulgaria. (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic E-mail: [email protected] resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory 2017/1069: received 3 June 2017, revised 27 substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of August 2017 and accepted 25 September test strains and those of four GLB strains were active against >71% of 2017 antibiotic resistant strains.
  • Targeting Virulence Not Viability in the Search for Future Antibacterials

    Targeting Virulence Not Viability in the Search for Future Antibacterials

    Targeting Virulence not Viability in the Search for Future Antibacterials 1 Begoña Heras1#, Martin J. Scanlon2,3# and Jennifer L. Martin4#* 1La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia 2Faculty of Pharmacy and Pharmaceutical Sciences, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052 Australia 3ARC Centre of Excellence for Coherent X-ray Science, Monash University, Parkville, VIC 3052 Australia 4The University of Queensland, Institute for Molecular Bioscience, Division of Article Chemistry and Structural Biology, Brisbane, QLD 4072 Australia #Contributed equally * To whom correspondence should be addressed: Email: [email protected] Phone +61 7 3346 2016 Running Head: Antivirulence Strategies for Bacterial Infection Keywords: Antivirulence; antibacterial; bacterial infection, pilicide, quorum sensing Word Count (excluding title page, summary, references, tables, figures) 2405 Number of Tables: 1 Number of Figures: 3 This article has been accepted for publication and undergone full peer review but has not been through theAccepted copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12356 1 This article is protected by copyright. All rights reserved. ABSTRACT New antibacterials need new approaches to overcome the problem of rapid antibiotic resistance. Here we review the development of potential new antibacterial drugs that do not kill bacteria or inhibit their growth, but combat disease instead by targeting bacterial virulence. INTRODUCTION In the ongoing battle between people and pathogens, the pendulum seems to be swingingArticle in favour of the bugs.
  • Resilience of Microbial Communities After Hydrogen Peroxide Treatment of a Eutrophic Lake to Suppress Harmful Cyanobacterial Blooms

    Resilience of Microbial Communities After Hydrogen Peroxide Treatment of a Eutrophic Lake to Suppress Harmful Cyanobacterial Blooms

    microorganisms Article Resilience of Microbial Communities after Hydrogen Peroxide Treatment of a Eutrophic Lake to Suppress Harmful Cyanobacterial Blooms Tim Piel 1,†, Giovanni Sandrini 1,†,‡, Gerard Muyzer 1 , Corina P. D. Brussaard 1,2 , Pieter C. Slot 1, Maria J. van Herk 1, Jef Huisman 1 and Petra M. Visser 1,* 1 Department of Freshwater and Marine Ecology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, 1090 GE Amsterdam, The Netherlands; [email protected] (T.P.); [email protected] (G.S.); [email protected] (G.M.); [email protected] (C.P.D.B.); [email protected] (P.C.S.); [email protected] (M.J.v.H.); [email protected] (J.H.) 2 Department of Marine Microbiology and Biogeochemistry, NIOZ Royal Netherland Institute for Sea Research, 1790 AB Den Burg, The Netherlands * Correspondence: [email protected]; Tel.: +31-20-5257073 † These authors have contributed equally to this work. ‡ Current address: Department of Technology & Sources, Evides Water Company, 3006 AL Rotterdam, The Netherlands. Abstract: Applying low concentrations of hydrogen peroxide (H2O2) to lakes is an emerging method to mitigate harmful cyanobacterial blooms. While cyanobacteria are very sensitive to H2O2, little Citation: Piel, T.; Sandrini, G.; is known about the impacts of these H2O2 treatments on other members of the microbial com- Muyzer, G.; Brussaard, C.P.D.; Slot, munity. In this study, we investigated changes in microbial community composition during two P.C.; van Herk, M.J.; Huisman, J.; −1 lake treatments with low H2O2 concentrations (target: 2.5 mg L ) and in two series of controlled Visser, P.M.
  • Hepatotoxicity-Induced by the Therapeutic Dose of Acetaminophen and the Ameliorative Effect of Oral Co-Administration of Selenium/ Tribulus Terrestris Extract in Rats

    Hepatotoxicity-Induced by the Therapeutic Dose of Acetaminophen and the Ameliorative Effect of Oral Co-Administration of Selenium/ Tribulus Terrestris Extract in Rats

    Int. J. Morphol., 38(5):1444-1454, 2020. Hepatotoxicity-Induced by the Therapeutic Dose of Acetaminophen and the Ameliorative Effect of Oral Co-administration of Selenium/ Tribulus terrestris Extract in Rats Hepatotoxicidad Inducida por la Dosis Terapéutica de Acetaminofén y el Efecto de Mejora de la Administración Conjunta de Extracto de Selenio Tribulus terrestris en Ratas Amin A. Al-Doaiss1,2 AL-DOAISS, A. A. Hepatotoxicity-induced by the therapeutic dose of acetaminophen and the ameliorative effect of oral co-administration of selenium / Tribulus terrestris extract in rats. Int. J. Morphol., 38(5):1444-1454, 2020. SUMMARY: Over dose or long-term clinical use of therapeutic doses of acetaminophen (APAP) causes hepatotoxicity. Various strategies attempted to ameliorate APAP-hepatotoxicity have been found to be unsuitable for clinical practice. This study was aimed to illustrate the histopathological changes induced by therapeutic dose of APAP and investigate the hepatoprotective role of oral co- administration of selenium/ Tribulus terrestris (TT) extract concurrently against hepatotoxicity induced by APAP in rats. Fifty-four healthy male albino Wistar rats were randomized into nine groups (G1–G9) of six rats each, and administered with APAP and TT orally for 30 days as follows: Control (2ml normal saline), APAP (470 mg/kg), APAP (470 mg/kg) + selenium (2 mg/kg), APAP (470 mg/kg) + TT (98 mg/kg), APAP (470 mg/kg) + selenium (2mg/kg) + TT (98 mg/kg), APAP (470 mg/kg) + silymarin (200 mg/kg), selenium (2 mg/ kg), TT (98 mg/kg) and silymarin (200 mg/kg) groups. The results demonstrated that exposure of rats to therapeutic dose of APAP for 30 days caused significant histopathological changes parallel to elevated blood chemistry parameters.
  • Significance of Donor Human Milk

    Significance of Donor Human Milk

    fmicb-09-01376 June 26, 2018 Time: 17:31 # 1 ORIGINAL RESEARCH published: 27 June 2018 doi: 10.3389/fmicb.2018.01376 Preterm Gut Microbiome Depending on Feeding Type: Significance of Donor Human Milk Anna Parra-Llorca1, María Gormaz1,2, Cristina Alcántara3, María Cernada1,2, Antonio Nuñez-Ramiro1,2, Máximo Vento1,2*† and Maria C. Collado3*† 1 Neonatal Research Group, Health Research Institute La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain, 2 Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain, 3 Department of Biotechnology, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia, Spain Preterm microbial colonization is affected by gestational age, antibiotic treatment, type of birth, but also by type of feeding. Breast milk has been acknowledged as the gold standard for human nutrition. In preterm infants breast milk has been associated with improved growth and cognitive development and a reduced risk of necrotizing enterocolitis and late onset sepsis. In the absence of their mother’s own milk (MOM), pasteurized donor human milk (DHM) could be the best available alternative due to its similarity to the former. However, little is known about the effect of DHM upon preterm Edited by: Sandra Torriani, microbiota and potential biological implications. Our objective was to determine the University of Verona, Italy impact of DHM upon preterm gut microbiota admitted in a referral neonatal intensive Reviewed by: care unit (NICU). A prospective observational cohort study in NICU of 69 neonates Carlotta De Filippo, <32 weeks of gestation and with a birth weight ≤1,500 g was conducted.