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Normal Microbiota: Locations and Predominant Microbes Skin Eye (conjunctiva) Oral cavity Teeth Subgingiva Respiratory Tract Nostrils Sinuses Upper respiratory tract Lower respiratory tract Gastrointestinal Tract Upper GI Tract Small Intestine Large Intestine Urogenital Tract Predominant Microbes Staphylococcus epidermidis, Micrococcus, Corynebacterium Staphylococcus epidermidis, Propionibacterium acnes Oral cavity Streptococcus mutans, Streptococcus sanguis Anaerobic bacteria (e.g., Actinomyces) Respiratory Tract S. epidermidis, Corynebacterium, Staphylococcus aureus Usually sterile Many (non-Beta hemolytic streptococci, Neisseria) Sparse Gastrointestinal Tract Helicobacter pylori Sparse (Lactobacillus, Micrococcus) G- coliforms, G+ enterococci, Clostridium, methanogens Lactobacillus acidophilus, S. epidermidis, Enterococcus Normal Microbiota: Benefits and Detriments Benefits • Compete with pathogens for attachment sites and resources. • Stimulate cross-reactive antibodies. • Antagonize potential pathogens through the production of antimicrobial chemicals. • Synthesize vitamins (K, B12, other B vitamins) and energy. Detriments • Dental caries and gingivitis. • Opportunistic pathogens o Normal microbes in the wrong place o Normal microbes with additional genes (plasmids or prophage) o Immunocompromised individuals Steps to Pathogenicity Transmission Direct contact Indirect contact (spread by fomites) Droplet contact (airborne within 1 meter) 1. Transmission 2. Colonization 3. Evasion from host defenses 4. Toxicity Vehicle Transmission (food, water, airborne > 1M) Mechanical vector Biological vector Colonization Evasion of Host Defenses Bacterial Cell 1a. Nonspecific adhesion due to hydrophilic interactions, Brownian motion, van der Waals forces. Evading phagocytosis Invading tissues where phagocytes do not patrol “Hiding” in host antigens (staphylococcal coagulase, Treponema fibronectin) Evasion of phagolysosome digestion 1b. Specific adhesion due to binding of bacterial adhesins (e.g., surface proteins, lipoteichoic acid, lipopolysaccharide) to host cell receptor sites. 2. Secretion of Invasins which are proteins that allow bacteria to invade host tissues and/or cells. Hyaluronidase and Collagenase which break down hyaluronic acid and collagen (which connect host cells together) Inhibition of lysosome action (Salmonella, Mycobacterium, Chlamydia) Escape from phagosome (Ricketssia) Killing phagocytes (hemolysins) Induction of ineffective antibodies Antigenic variation Bacterial Kinases prevent clotting of blood. Host Tissue Neuraminidase destabilizes host cell membrane and enhances intracellular invasion. Bacterial Toxins Exotoxins Exotoxin Lysogenic conversion A-B toxin. Inhibits protein synthesis. Cytotoxin. + • Streptococcus pyogenes Membrane-disrupting. Erythrogenic. + • Clostridium botulinum A-B toxin. Neurotoxin + • Corynebacterium diphtheriae Source Gram– Source Mostly Gram+ (but also G-) Metabolic product Metabolic product LPS (Lipid A) of cell wall By-products of growing cell Chemistry Lipid Symptoms Fever?Inflammation Fever, Shock, Various but specific • C. tetani A-B toxin. Neurotoxin Toxoid Formation No Neutralized by antitoxin LDlarge 50 Relatively Yes • Vibrio cholerae A-B toxin. Enterotoxin Small • Staphylococcus aureus LD50 Chemistry Protein Superantigen. Enterotoxin. + Extent of Host Involvement Classifying Infectious Diseases • Local infection Pathogens limited to a small area of the body • Systemic infection An infection throughout the body • Bacteremia Bacteria in the blood • Septicemia Growth of bacteria in the blood • Toxemia Toxins in the blood • Viremia Viruses in the blood • Primary infection Acute infection that causes the initial illness • Secondary infection Opportunistic infection after a primary infection • Subclinical disease No noticeable signs or symptoms (inapparent infection) Communicable disease A disease that is spread from one host to another. Contagious disease A disease that is easily spread from one host to another. Noncommunicable disease A disease that is not transmitted from one host to another. Endemic disease Disease constantly present in a population. Epidemic disease Disease acquired by many hosts in a given area in a short time. Pandemic disease Worldwide epidemic. Herd immunity Immunity in most of a population. Nosocomial (Hospital-Acquired) Infections The Stages of a Disease Are acquired as a result of a hospital stay 5-15% of all hospital patients acquire nosocomial infections Why are nosocomial infections so prevalent? Pathogenic microbes present in health care settings Immunocompromised patients present in health care settings Multiple modes of transmission (air, puncture wounds, direct contact) Why are nosocomial infections so dangerous? Multiply antibiotic resistant strains Sequela Figure 14.5