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Organism Classification Based upon morphology and biochemical characteristics Nature of the cell wall (rigid, flexible, absent) Shape (cocci, bacilli) Staining characteristics (gram-positive or gram-negative) Oxygen requirements (aerobe, anaerobe, facultative) Classification...

Organism Classification Based upon morphology and biochemical characteristics Nature of the cell wall (rigid, flexible, absent) Shape (cocci, bacilli) Staining characteristics (gram-positive or gram-negative) Oxygen requirements (aerobe, anaerobe, facultative) Classification Aerobic Anaerobic Oxygen Effect ------------------------------ ---------------------- ----------- -------------------------- 1\) **Obligate aerobe** Growth No growth Required 2\) **Obligate anaerobe** No growth Growth Prevents growth 3\) **Facultative anaerobe** Growth Growth Faster growth 4\) **Microaerophile** Growth (unless high) No growth Required but \< 20% 5\) **Aerotolerant** Growth Growth Not required or utilized Ability to form spores Free-living (can be cultured) vs. non-free living (obligate intracellular parasites) Organism-specific tests (coagulase, oxidase) Definitive classification of genus according to base sequence of the DNA Example: *Pseudomonas cepacia* *Burkholderia cepacia* Example: *Pseudomonas maltophilia* *Xanthomonas maltophilia* *Stenotrophomonas maltophilia* Normal flora (human microbiome) Organisms (bacteria/fungi) that are permanent residents of certain anatomic sites (nonpathogenic) Commensals -- derive benefit from host without causing harm (low virulence) Carrier state -- presence of an organism that is a potential pathogen without overt symptoms Colonization -- acquisition of a new organism that could infectious disease Sites: Skin, oropharynx, colon, vagina (vary in number and type of organism) Normally sterile sites: CNS, Blood, Lower respiratory tract, liver, spleen, kidneys, bladder, stomach due to pH, body cavities Viruses and parasites [not] considered normal flora (may be present as asymptomatic disease) Role of normal microbiome in health Protective host defense mechanism (colonization resistance) -- protects from growth of pathogens Antibiotic therapy leading to *clostridium difficile* infection Nutritional function -- produce B vitamins and vitamin K Antibiotic therapy leading to a change in INR in a patient receiving warfarin Role of normal microbiota in disease Immunocompromised / debilitated patients Presence in location outside their normal location Key Members of the Normal Flora +-----------------+-----------------+-----------------+-----------------+ | Etiology | Key Organism(s) | Key Infections | Other | | | | | Organism(s) | +=================+=================+=================+=================+ | Skin | *Staphylococcus | Prosthetic | *Propionibacter | | | epidermidis | heart valves | ium | | | Staphylococcus | | acnes* | | | aureus* | Prosthetic | | | | | Joint | *Corynebacteriu | | | *Streptococcus | | m | | | sp.* | Surgical site | species* | | | | infections | | +-----------------+-----------------+-----------------+-----------------+ | Oropharynx | *Streptococcus | Endocarditis | *Staphylococcus | | (mouth) | (viridans | | aureus (nasal)* | | | group) | Dental plague | | | | Neisseria | (caries -- *S. | *Peptostreptoco | | | species* | mutans*) | ccus | | | | | sp. (oral | | | *Corynebacteriu | | anaerobes)* | | | m | | | | | sp. | | *Prevotella and | | | (diptheroids)* | | Fusobacterium | | | | | sp.* | | | *S. | | | | | epidermidis* | | *Eikenella | | | | | corrodens* | | | *Haemophilus | | (human bites) | | | sp.* | | | +-----------------+-----------------+-----------------+-----------------+ | Small intestine | *Streptococci | Bacteremia | *N/A* | | | sp.* | | | | | | | | | | *Lactobaccillus | | | | | species* | | | | | | | | | | *Candida | | | | | albicans* | | | +-----------------+-----------------+-----------------+-----------------+ | Large intestine | *Bacteroides | Urinary tract | *Pseudomonas | | (colon) | fragilis* | infections (*E. | aeruginosa* | | | (other | coli*) | | | | anaerobes) | | *Clostridium | | | | Peritonitis | difficile* | | | *Escherichia | (*B. fragilis*) | | | | coli* | | *Candida | | | (coliforms) | Endocarditis | albicans* | | | | (*E. faecalis)* | | | | *Enterococcus | | | | | faecalis* | | | | | | | | | | *Lactobacillus | | | | | species* | | | +-----------------+-----------------+-----------------+-----------------+ | Genitourinary | *Lactobacillus | Rarely cause | *Candida | | tract | species* | infection | albicans-yeast | | | (vagina) | | infection* | | | | | | | | *Gardnerella | | *Group B | | | vaginalis* | | Streptococcus* | | | (vagina) | | | | | | | *Staphylococcus | | | Staphylococcus | | aureus* | | | sp. (urethra) | | | | | | | *Staphylococcus | | | | | saphrophyticus* | | | | | | | | | | *Fecal flora* | +-----------------+-----------------+-----------------+-----------------+ Pathogenesis- can cause disease Definitions: [Pathogen] -- capable of causing disease Opportunistic -- capable of causing disease in patient with reduced host defenses (includes normal flora) Virulence -- likelihood of causing disease ([virulence factors] of the organism play a significant role) LD~50~ -- number of organism (inoculum) needed to kill 50% of the infected hosts ID~50~ -- number of organisms needed to infect 50% of the exposed hosts Acquisition of the infection Balance between the organism and the host defense Number of organisms (inoculum) Virulence of the organism (also influences type of infection) Innate and acquired immunity Asymptomatic (inapparent) infection -- exposure to the organism, but the host defense prevents symptomatic disease Type of infections "Infection" -- may be symptomatic or asymptomatic Main mechanisms of symptoms Toxin production -- does not require actual presence of the organism Exotoxin -- polypeptides released by the organism Endotoxin -- lipopolysaccharides (LPS) from cell wall Invasion and proliferation of the organism with resulting [inflammatory response] Infection-related terms Communicable -- ability to be spread from host to host Contagious -- highly communicable Epidemic -- occurring more frequently than usual Pandemic -- worldwide distribution Endemic -- constantly present at a low level in a population Latent -- Asymptomatic period where the organism is dormant -- reactivation and recurrence at any time Pathogenic staging Transmission through a portal of entry (unless acquired through normal flora or colonization) Evasion of the primary host defense **Adherence to mucous membranes** **Colonization at the site of adherence** **Symptoms by toxin or generalize inflammatory response** Host response will occur during the **bolded** steps Disease progression or resolution Transmission \*WILL BE TEST QUESTIONS\* Interruption of the chain of transmission critical in infection control Human-to-Human Direct contact Indirect contact (air, fecal-oral) Transplacental (**vertical**) -- transplacetal, birth canal, breast milk bloodborne Nonhuman sources Fomites -- inanimate objects that serve as a source for bacteria Soil and water sources Food Insect vectors Animal (Zoonotic) sources (direct, vector, excrement) Portals of entry (respiratory tract, gastrointestinal tract, genital tract, skin) Adherence to cell surfaces mediated by [adhesins (WONT BE ON TEST)] Pili, capsules, glycocalyces Biofilm -- polysaccharide and protein complex produced by bacteria Protects from immune system Decreased antibiotic penetration Curli -- protein that promotes adherence and activates factor XII allow thrombus formation Invasion, inflammation and Intracellular survival (often clustered into pathogenicity islands) WONT BE ON TEST Virulence factors (enzymes) promoting invasion Collagenase and hyaluronidase Coagulase Immunoglobulin A (IgA) protease Leukocidins Virulence factors limiting host defense Polysaccharide capsule (prevents opsonization) M protein -- antiphagocytic Protein A -- binds IgG and inhibits complement activation Types of inflammation Pyogenic -- neutrophils Granulomatous -- macrophages and T cells Intracellular invasion Invasins -- allow binding of organism to host cell Actin microfilaments (actin rockets) -- allow movement from host cell to host cell Intracellular survival Inhibits fusion of phagosome with lysosome Inhibits phagosome acidification Escape from the phagosome Toxin production Exotoxins Secretion systems -- can be secreted into the environment or directly into a host cell (injectosomes) A-B subunits (Active and Binding units) Important mechanisms ADP-ribosylation -- can increase or decrease cAMP through G~s~ or G~i~ factors Superantigen -- overproduction of cytokines Protease Lecinthinase -- disrupts cell membrane Neurotoxin Enterotoxin Examples of organisms includes: *Clostridium sp.; Bacillus anthracis; Staphylococcus aureus; Streptococcus pyogenes; Escherichia coli; Shigella dysenteriae; Vibrio cholerae; Bordetella pertussis* Sites of toxin effects: gastrointestinal tract; nervous system; respiratory tract; skin/soft tissue/muscle; systemic effects Endotoxins (primarily Lipid A) Lead to generalized effects of fever, capillary leak, vasodilation and hypotension Macrophage activation Interleukin-1 (IL-1) fever Tumor necrosis factor (TNF) fever, capillary leak Nitric oxide vasodilation Complement activation C3a capillary leak and vasodilation C5a neutrophil chemotaxis Tissue factor activation Coagulation cascade disseminated intravascular coagulation Gram positive organisms -- similar effect due to lipoteichoic acid Comparison of toxins Property Exotoxin Endotoxin --------------------- ------------------------------- ----------------------------------- Source Gram(+) and Gram(--) bacteria Cell wall of gram(--) bacteria Secreted Yes No Chemistry Polypeptide Lipopolysaccharide Gene Plasmid or bacteriophage Bacterial chromosome Toxicity High Low Effects Vary by toxin Fever, inflammation Mechanism of action Vary by toxin Inflammatory mediators (TNF, IL1) Antigenicity Induces antibodies Poorly antigenic Vaccines Toxoids used as vaccine None Heat stability Heat labile Stable Typical diseases Tetanus, Botulism, Diphtheria Gram(--) sepsis, meningococcemia Other Factors Different strains of the same bacteria can cause different infections -- depends upon what virulence factors are present Immunopathogenesis -- results in an autoimmune reaction with certain tissues (nephron, heart valves) Cancer Typical stages of infection

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