Microbial Pathogens Lecture Notes PDF

MICROBIAL PATHOGENS Prof Dave Scanlan  Microbial Pathogens Terminology: A pathogen is a microorganism that is able to cause disease in a plant, animal or insect. Pathogenicity is the ability to produce disease in a host organism. Microbes express their pathogenicity...

MICROBIAL PATHOGENS Prof Dave Scanlan  Microbial Pathogens Terminology: A pathogen is a microorganism that is able to cause disease in a plant, animal or insect. Pathogenicity is the ability to produce disease in a host organism. Microbes express their pathogenicity by means of their virulence, a term which refers to the degree of pathogenicity of the microbe. Hence the determinants of virulence of a pathogen are any of its genetic or biochemical or structural features that enable it to produce disease in a host. The relationship between a host and a pathogen is dynamic, since each modifies the activities and functions of the other. The outcome of an infection depends on the virulence of the pathogen and the relative degree of resistance or susceptibility of the host, due mainly to the effectiveness of the host defense mechanisms.  The Underlying Mechanisms of Bacterial Pathogenicity Two broad qualities of pathogenic bacteria underlie the means by which they cause disease: 1. The ability to invade tissues: Invasiveness, which encompasses mechanisms for colonization (adherence and initial multiplication), ability to bypass or overcome host defense mechanisms, and the production of extracellular substances which facilitate invasion. e.g. adhesins like fimbriae (filamentous proteins on the bacterial cell surface) 2. The ability to produce toxins: Toxigenesis. Bacteria produce two types of toxins called exotoxins and endotoxins. Exotoxins are released from bacterial cells and may act at tissue sites removed from the site of bacterial growth. e.g. Botulinum or Cholera toxin. Endotoxins are cell-associated substances that are structural components of the cell walls of Gram-negative bacteria e.g. capsule or LPS  Establishment of infection For human pathogens entry into the body can occur through Respiratory- Gastro-intestinal- Urinary- or Genital-tracts Or by insect bites or by accidental or surgical trauma to the skin Many opportunistic pathogens are carried as part of the normal human flora – acts as a ready source of infection in the compromised host For primary pathogens transmission is more complex : Transmission of Bordetella pertussis (respiratory pathogen) requires contact with infectious material since this organism survives poorly in the environment while for sexually transmitted diseases e.g. Neisseria gonorrhoeae direct person-to-person mucosal contact is required – man is the only natural host for this pathogen which dies rapidly in the environment  Medically important Pathogens and their Environment For many gastro-intestinal pathogens e.g. Salmonella, Shigella and Campylobacter species the primary source is environmental, and infection follows ingestion of contaminated food or water These (and other) pathogens hence need to remain viable in different environmental conditions The environments that can be colonised by a pathogen are critical in determining its reservoirs and potential modes of transmission Importantly individual bacteria are not restricted to a single physiological state but can respond to environmental stimuli and undergo adaptive responses which confer improved capacity for survival in adverse conditions Bacterial pathogen physiology with respect to its environment Constraints of the physical environment: Temperature adaptation (Lecture 1) pH tolerance (Lecture 2) Anaerobiosis (Lecture 3) MICROBIAL PATHOGENS Prof Dave Scanlan Additional References: Lecture 1 Zhang Y., and Gross C.A. (2021) Cold shock response in bacteria. Ann. Rev. Genetics 55: 377-400. Bierne H., and Cossart P. (2007) Listeria monocytogenes surface proteins from genome predictions to function. Microbiol. Mol. Biol. Rev. 71: 377-397. Hamon, M., Bierne, H., and Cossart, P. (2006) Listeria monocytogenes: a multifaceted model. Nature Rev. Microbiol. 4: 423-434. Swanson MS, Hammer BK (2000). Legionella pneumophila pathogenesis: A fateful journey from amoebae to macrophages. Ann. Rev. Microbiol. 54: 567-613. Lecture 2 Ernst PB, Gold BD (2000) The disease spectrum of Helicobacter pylori : The immunopathogenesis of gastroduodenal ulcer and gastric cancer. Ann. Rev. Microbiol. 54: 615-640. Booth IR, Cash P, O'Byrne C. (2002) Sensing and adapting to acid stress. Antonie van Leeuwenhoek 81: 33-42. Cotter, P.D., and Hill, C. (2003) Surviving the acid test: responses of Gram-positive bacteria to low pH. Microbiol. Mol. Biol. Rev. 67: 429-453. Lecture 3 Bacterial Pathogenesis: A Molecular Approach. Salyers, AA and Whitt DD 2 nd Edition, ASM Press. Chapter 24 Clostridium The Effect of Temperature on Growth and Pathogenicity Terminology Psychrophiles Optimal Growth Temperatures Listeria Legionella  Terms used to describe microorganisms in relation to temperature requirements for growth Group Minimum Optimum Maximum Comments Grow best at Psychrophile below 0C 10-15C below 20C relatively low T Able to grow at low T Psychrotroph 0C 15-30C above 25C but prefer moderate T Most bacteria esp. those living in Mesophile 10-15C 30-40C below 45C association with warm-blooded animals Among all above 100C thermophiles is wide Thermophile 45C 45-70C (boiling) variation in optimum and maximum T Most bacteria will grow over a temperature range of about 30 C. The curves exhibit three cardinal points: minimum, optimum and maximum temperatures for growth. There is a steady increase in growth rate between the minimum and optimum temperatures, but slightly past the optimum a critical thermolabile cellular event occurs, and the growth rates plunge rapidly as the maximum T is approached. Growth rate versus temperature for different classes of bacteria  Minimum, maximum and optimum temperature for growth of certain bacteria and archaea Bacterium Minimum Optimum Maximum Listeria monocytogenes 1 30-37 45 Vibrio marinus 4 15 30 Vibrio cholerae 18-37 Pseudomonas maltophila 4 35 41 Thiobacillus novellus 5 25-30 42 Staphylococcus aureus 10 30-37 45 Escherichia coli 8 37 45 Clostridium kluyveri 19 35 37 Streptococcus pyogenes 20 37 40 Streptococcus pneumoniae 25 37 42 Bacillus flavothermus 30 60 72 Thermus aquaticus 40 70-72 79 Methanococcus jannaschii 60 85 90 Solfolobus acidocaldarius 70 75-85 90 Pyrobacterium brockii 80 102-105 115 Cold shock and adaptation e.g. in E.coli a downshift in T causes a transient inhibition of most protein synthesis – causes a growth lag known as the acclimation phase during the acclimation phase a group of cold shock proteins (Csp) are dramatically induced Some of these cold shock proteins are essential for the cell to resume growth at low temperature Bioessays (1998) 20: 49-57  E. coli Cold Shock Proteins Protein Putative function Class I (>10-fold induction) CspA family CspA RNA chaperone CspB RNA/DNA chaperone (?) CspG RNA/DNA chaperone (?) CsdA 70-kDa ribosome-associated protein (RNA unwinding activity) Rbf A 15-kDa 30S ribosomal binding factor NusA Involved in termination and anti-termination PNP Ribonuclease Class II (