Lec#18 .pptx

PowerPoint® Lecture Presentations CHAPTER 24, 25 Microbial Interactions with humans: Symbiosis and Infections and pathogenesis © 2018 Pearson Education, Inc. Normal microflora • Hundreds of species of microorganisms grow on or in the human body! • Each person has a unique microbiome • Normal...

PowerPoint® Lecture Presentations CHAPTER 24, 25 Microbial Interactions with humans: Symbiosis and Infections and pathogenesis © 2018 Pearson Education, Inc. Normal microflora • Hundreds of species of microorganisms grow on or in the human body! • Each person has a unique microbiome • Normal microflora have a symbiotic relationship with their host • Produce beneficial products & inhibit growth of dangerous microorganisms • Host provides microenvironment that supports microbial growth • Mammals develop in a microbially sterile environment in utero – colonization begins during birth • Microbes readily colonize skin, oral cavity, upper respiratory tract & GI tract Opportunists are microbes that can cause disease in certain situations. Candida albicans, a yeast, lives in the mouth, but can cause oral disease (thrush) in people who are undergoing cancer therapy or are taking broad spectrum antibiotics. E. coli is an intestinal bacterium that can cause disease when transferred to other body regions. Oral streptococci can cause heart disease if they enter the bloodstream. Pneumocystis carinii occurs in the respiratory tract but can cause lethal pneumoniae in AIDS patients. P. 3 aeruginosa occur in soil. Microbial pathogenesis • The process by which microorganisms cause disease • Infection: Growth of microorganisms that are not normally present within the host • Disease: Tissue damage or injury that impairs host function Pathogen Transmission • four main modes of transmission • Airborne--sneezing • Contact– pregnancy (vertical transmission) • Vehicle—food • Vector borne—ticks, mosquitoes, fleas 5 Microbial pathogenesis • Pathogenicity (ability to cause disease) differs considerably among pathogens • Opportunistic pathogens cause disease only in the absence of normal host resistance • Even normal microflora may cause disease when host resistance is compromised • Pathogenicity is measured by virulence • = Relative ability of a pathogen to cause disease • Outcome of dynamic relationship between host and pathogen Measuring virulence • Experimental studies determine lethal dose50 (LD50) • Number of cells of a pathogen that kills 50% of the animals in a test group • Highly virulent pathogens show little difference in number of cells required to kill 50% vs. 100% Virulence genes Encode factors allowing pathogen to invade host •Toxins, attachment proteins, capsules Virulence Factors Pathogenicity islands Section of genome •Contain multiple virulence genes •Often encode related functions •e.g. Protein secretion system, toxin production -Transferred as a block from other organisms •Often flanked by phage or plasmid genes •Often have GC-content different from rest of genome 8 Adherence • Ability of a microorganism to attach to a cell or surface • Bacteria & viruses adhere to epithelial cells through specific interactions with molecules on host tissues • May also adhere to each other, forming a biofilm • Some bacteria secrete extracellular polymers that coat their surface and facilitate attachment • Capsules & slime layers • E.g. Bacillus anthracis contains a capsule composed of a polymer of D-glutamic acid Colonization sites • Colonization typically begins in mucous membranes • Tightly packed epithelial cells that interface with the external environment • Line urogenital, respiratory & GI tracts • Epithelial cells secret mucus • Thick liquid secretion containing proteins and glycoproteins • Retains moisture Mucus Microbial cells Epithelial cell Colonization Attachment of enteropathogenic E. coli to brush border of intestinal microvilli through a distinct capsule Attachment of Vibrio cholerae to brush border without a capsule. Capsules • Capsules are also important for protecting pathogenic bacteria from host defense mechanisms • S. pneumoniae with capsule infects lungs and leads to pneumonia • Can cause extensive host damage or even death • Nonencapsulated strains are quickly destroyed by the immune system & do not cause infection Invasion • The initial inoculum of a pathogen is usually insufficient to cause host damage • Must find appropriate nutrients & environmental conditions to multiply and cause infection • Invasion = The ability of a pathogen to enter into host cells or tissues, spread, and cause disease • Pathogen entry often begins at breaks or wounds in skin or mucous membranes • Growth may also begin on intact mucosal surfaces, especially if normal flora is compromised Infection & Disease • Infection: Any situation in which a microorganism (not a member of the local flora) is established and growing in a host • Requires that host environment supplies adequate nutrients for growth • Disease: Tissue damage or injury that impairs host function • Some pathogens remain localized after initial entry, producing a single focus of infection • Some pathogens may spread throughout the body • Bacteremia: the presence of bacteria in the bloodstream • Septicemia: bloodborne systemic infection • May lead to massive inflammation, septic shock, and death Virulence in Salmonella • Salmonella species encode a large number of virulence factors, which are often found clustered together in chromosomal pathogenicity islands • Facilitates horizontal transfer • Pathogenicity island 1 (SPI1) is a cluster of 10 genes that promote invasion • Surface adhesion proteins, trafficking & secretion of virulence proteins • SPI2 contains genes that promote systemic disease & resistance to host defenses • Additional virulence factors & antibiotic resistance genes carried on R plasmids Enterotoxin (diarrhea) Injectisome (inv and prg products form complex) Endotoxin in LPS layer (fever) Siderophores (iron uptake) Type Ι fimbriae (adherence) SPΙ2 SPΙ1 Antiphagocytic proteins induced by oxyR O antigen (inhibits phagocyte killing) Virulence plasmid Cytotoxin (inhibits host cell protein synthesis; Ca2+ efflux from host cell; adherence) Vi capsule antigen; inhibits complement binding Pathogenicity islands on chromosome Flagellum (motility) H antigen (adherence; inhibits phagocyte killing) Toxins • Toxicity: Ability of an organism to cause disease by means of a preformed toxin that inhibits host cell function or kills host cells • Exotoxins: Toxic proteins released from the pathogen as it grows, producing immediate host cell damage • Three categories: Cytolytic toxins, AB toxins, superantigen toxins • Enterotoxins: A subset of exotoxins whose activity affects the small intestine • Generally causes secretion of fluid into the intestinal lumen • Results in vomiting and diarrhea © 2008 W.W. Norton & Company, Inc. MICROBIOLOGY 1/e 18 RCSB PDB 3ANZ Staphylococcal α-toxin Cytoplasmic membrane Influx of extracellular components Efflux of cytoplasmic components α-Toxin pore Out In AB Toxins • Consist of two subunits, A and B • Work by binding to host cell receptor (B subunit) and transferring a damaging agent (A subunit) across the cell membrane • e.g. Diphtheria toxin • AB is a single subunit • B binds to receptor & proteolytic cleavage allows A to move across cell membrane • A disrupts protein synthesis by inactivating elongation factor 2 • Encoded by a viral gene from the lysogenic bacteriophage β • An example of phage conversion Toxins Subvert Host Function • AB Toxins • B subunit binds to host cell • Delivers A subunit to cell • Often 5 B subunits form a pore for A entry • A subunit has toxic activity • ADP-Ribosyltransferase • Diphtheria toxin • Cholera toxin Vibrio cholerae 21 Diphtheria Toxin Cytoplasmic membrane A EF-2 A A Receptor protein A 2* EF- A T G A A tRN T Ribosome Normal protein synthesis In EF-2* 2 EF- Amino acid B Diphtheria toxin Out B Protein synthesis stops A tRN G Botulinum toxin • Clostridium botulinum: Endospore-forming bacteria commonly found in soil • Produces highly poisonous AB exotoxins that function as neurotoxins • Frequently grows & produces toxin in improperly preserved foods • Botulism often caused by ingestion of preformed toxin • Toxin consists of two components – one that allows entry into a neuron, and one that blocks release of acetylcholine • Prevents impulse transmission and blocks muscle contraction • Infant botulism occurs in newborns under 2 months • Ingested C. botulinum endospores germinate in intestine & produce toxin • Due to lack of well-developed microflora Botulinum toxin Superantigen toxins • Stimulate significantly more immune cells than normal, resulting in an inappropriately strong inflammatory immune response • Results in extensive inflammation and tissue damage • Fever, diarrhea, vomiting, mucus production and systemic shock that may be fatal • e.g. S. aureus toxic shock syndrome toxin, which can cause systemic shock & death • e.g. S. pyogenes erythrogenic toxin, which causes scarlet fever Endotoxins • The lipopolysaccharide (LPS) portion of the cell envelope of certain gram-negative Bacteria • Structural cell-bound component rather than secreted soluble product • Lipid A portion of LPS is responsible for toxicity, while polysaccharide fraction makes complex water-soluble • Must be delivered as a unit for toxicity • LPS stimulates immune cells to release cytokines that cause fever, vomiting, diarrhea, and inflammation • Generally less toxic than exotoxins © 2008 W.W. Norton & Company, Inc. MICROBIOLOGY 1/e 28 The Compromised Host • One or more resistance mechanisms are inactive & the probability of infection is increased • Hospital patients may be compromised hosts • Invasive medical procedures, stress, anti-inflammatory drugs, immunosuppressive drugs • Healthcare-associated infections cause ~100,000 deaths /yr in US • Many factors can reduce host resistance • Smoking, excess consumption of alcohol, IV drug use, lack of sleep, poor nutrition, acute or chronic infection with another agent • Certain genetic conditions compromise the host