MICROBIAL PATHOGENICITY

SHE Level 5
SCQF Credit Points 15.00
ECTS Credit Points 7.50
Module Code MMC525253
Module Leader Karen Keith
School School of Health and Life Sciences
Subject Biological and Biomedical Sciences
Trimester
  • A (September start)

Pre-Requisite Knowledge

Good undergraduate degree in a relevant discipline

Summary of Content

This module examines at an advanced level the current understanding of the molecular mechanisms employed by microbial pathogens of humans in establishing infectious diseases and will focus on an in-depth appreciation on the cell biology of the host-pathogen relationship.

Syllabus

Lectures Pathogenicity and Bacterial Metabolism (10) Introduction to the cell envelope and secretion: GSP dependent pathways. Type II secretion, cholera toxin, Type IV secretion, pertussis toxin. The autotransporter pathway. GSP independent secretion. Yop proteins of Yersinia , ABC transporters and haemolysin secretion, twin arginine translocation complex. Synthesis of the Gram negative envelope. LPS synthesis as a drug target. Outer membrane protein assembly, OmpA OmpF and OmpC gene expression in response to osmotic change and environmental challenge. The role of the envelope in intrinsic and acquired resistance to antibiotics. Understanding efflux pumps in Gram negative bacteria. Iron as a key factor in the struggle between pathogen and host: iron uptake mechanisms in bacteria. The potential of using iron uptake mechanisms as drug targets. Pathogenicity and virulence (20) Introduction to pathogenicity and virulence: Overview of the chain of events in infectious disease, transmission of disease, portals of entry and first lines of defence. Adhesion mechanisms: structural and functional aspects of bacterial adhesion mechanisms of Gram negative and Gram positive bacteria. Immune evasion strategies to counteract innate defences, evasion of phagocytes, antigenic variation, countering complement and antibodies, role of capsules, LPS side chains and pili phase variation in S. pneumoniae, N. gonorrhoeae . Bacterial toxins in disease: Endotoxin structure and role in septic shock. Introduction to bacterial protein toxins; historical aspects, toxins produced by principal toxigenic bacteria. Quantitation of virulence (LD50) - importance in vivo . Staphylococcal and streptococcal toxins as immunomodulins - Enterotoxins of Vibrio cholerae and E. coli ; comparison of structures, molecular mechanisms of action, genetics, role in the pathogenesis of acute diarrhoeal disease. Invasive infections: Listeriosis and shigellosis. Genes and virulence factors involved in epithelial invasion by Shigella spp and Listeria monocytogenes ; tissue culture studies and comparison of models for in vivo invasion. Anaerobic pathogens: the structure and mode of action of the large clostridial toxins from C. tetani and C. botulinum . The virulence mechanisms of C. difficile including toxins, their structure and mode of action. The role of the microbiome in protection from C. difficile infection. Tutorials (8) Student centred learning tutorials will encourage advanced understanding through study of papers relevant to topics including secretion systems in Mycobacteria. An in depth study of experimental methodology will provide the opportunity for critical reflection and evaluation of current experimental approaches. Tutorials will provide students with the opportunity for structured discussion involving student participation.

Learning Outcomes

On successful completion of this module, the student should be able to:1. Explain structure and mode of action of toxins that contribute to virulence of bacteria2. Recognise the importance of the Gram negative envelope 3. Demonstrate knowledge and understanding of mechanisms of microbial pathogenesis and the outcomes of infections4. Formulate methodology for studying virulence mechanisms5. Relate current knowledge and understanding of the multifactorial nature of microbial pathogenicity to the importance of host/pathogen interactions in disease.6. Discuss and appraise the experimental basis of knowledge in host/pathogen interactions, including learning and appreciation of the latest molecular techniques employed in conducting research and extrapolating laboratory findings to the actual disease.7. Critically analyse research papers.

Teaching / Learning Strategy

The lecture programme will present the latest concepts in microbial pathogenicity, incorporating current research literature, web sites and reviews. Tutorials will add to this by broadening specific issues to induce synthesis and critical understanding from students and examine applications for the fundamental knowledge acquired in lectures. Data analysis exercises will afford the opportunity to critically assess published data and promote an appreciation of the problems encountered with methodology employed in research. Self-directed study will be undertaken in a student centred learning package which will incorporate an understanding of complex and advanced techniques and practices in the study of microbial pathogenicity.

Indicative Reading

Reading material will be recommended by individual tutors and will include relevant recent scientific papers and reviews. However the following texts may be useful; -359b7 Salyers, A.A. and Whitt, D.D. (2010). Bacterial Pathogenesis. A Molecular Approach (2nd edition). ASM Press b7 Kim, B.H. and Gadd, G.M. (2008). Bacterial Physiology and Metabolism. Cambridge University Press. b7 Lax, A.J. (2005). Toxin: The Cunning of Bacterial Poisons. Pub Oxford University Press. b7 Nash, A. and Dalziel (2015). Mim's Pathogenesis of Infectious Disease (5th edition). Academic Press. b7 Tropp, B.E. (2011). Molecular Biology: Genes to Proteins (4th edition). Jones & Bartlett Publishers.

Transferrable Skills

Each student should develop a series of generic skills. These include the development of information retrieval skills using library and electronic resources, the ability review and critically analyse published data concerning cutting edge laboratory theory, communication of scientific information in an appropriate, logical and coherent fashion. Independent study skills are all integral components of the module.

Module Structure

Activity Total Hours
Tutorials (FT) 8.00
Assessment (FT) 10.00
Lectures (FT) 30.00
Independent Learning (FT) 102.00

Assessment Methods

Component Duration Weighting Threshold Description
Exam (Exams Office) 3.00 60.00 45% Unseen written examination to test learning. 4 out of 6 essay questions.
Exam (Dept) 02 1.00 15.00 45% Essay based on independent study of a topic related to lecture material.
Exam (Dept) 01 1.00 25.00 45% Data Analysis, interpretation of data and application of methodology presented in a recent paper.