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Medical Microbiology Chapter 19 Mechanisms of Bacterial Pathogenesis Terms Pathology – study of disease  Etiology – cause of disease  Pathogenesis – manner in which a disease develops  Infection – invasion or colonization of the body by pathogenic microorganisms  Disease – change from a state of health  Diseases   How are diseases catagorized? Spread: – Communicable – Contagious – Noncommunicable  Categorization according to how often they occur in a given location: – endemic - constantly present – epidemic - disease occurring in excess of normal expectancy – Pandemic - worldwide epidemic Disease  Severity or duration: – Acute – Chronic – Latent  Extent of infection: – Local infection – Systemic infection – Bacteremia, septicemia, toxemia, viremia Disease Primary infection vs. secondary infection  Subclinical infection  Spread of Disease   Etiology or etiological agent - cause of a disease Reservoir - continual source of pathogens – human, animal, non-living  Mechanisms of Transmission: – contact transmission - from one person to another person direct  indirect (through a fomite)  droplet (sneezing, coughing and talking)  Spread of Disease (cont.) – Vehicle Transmission - transmission of disease by a medium  water, food, air – Vector Transmission - transmission of disease by an insect  Nosocomial infections Epidemiology  Epidemiology is the study of the frequency and distribution of disease – Examples The CDC  The Centers for Disease Control and Prevention (CDC) is the nation’s center for epidemiology – The CDC tracks some 50 infectious diseases nationwide – they help county and state agencies during epidemics – The CDC publishes a weekly newsletter called Morbitity and Mortality Weekly Virulence Factors  Successful pathogens have a variety of factors that contribute to their ability to cause disease – these are called virulence factors Mechanisms of Pathogenesis  Successful pathogens carry out a sequence of events: – transmission to a susceptible host – gain access to the host – adherence to the target tissue – colonization and sometimes invasion – damage to the host – exit from the host – transmission to a new host Mechanisms of Pathogenesis  Transmission – Contact, vehicle, vector, etc.  Access – Portals of Entry – Mucous membranes – Skin – Parenteral Route – through damage to the skin or mucous membranes – Table 19.1 Adherence and Invasion  Adherence: – Adhesins   Many are found on fimbriae Table 19-2 – Capsules – Biofilms  Invasion – some pathogens can cross the mucous membranes Colonization  Colonization – bacteria can evade the immune system and replicate to cause disease. – Antiphagocytic structures:  Capsule – extremely important virulence factor – They are also poorly antigenic (polysaccharides)  Cell walls (mycobacteria) – Intracellular growth – Antigenic variation – changing of antigens – Inactivation of antibodies or complement Damage  Damage: – Enzymes – Toxins – Inappropriate Immune Responses  Exaggerated inflammation (endotoxin)  Cross-reactive antibodies - strep throat and rheumatic fever/glomerulonephritis Enzymes  Enzymes are released from cells and damage host tissues – Leukocidins - kill white blood cells – Hemolysins - cause the lysis of RBCs   b hemolysin - complete breakdown of RBCs a hemolysin - incomplete breakdown of RBCs – Streptokinase/Staphylokinase - breaks down blood clots  How could this be related to virulence? Enzymes (cont.) – Coagulase - causes the formation of blood clots almost all pathogenic strains of S. aureus produce this enzyme  How does this contribute to virulence?  – Collagenase - breaks down collagen  produced by the clostridia that cause gas gangrene – Proteases, hyaluronidase, phospholipase C, etc. Endotoxin  What is endotoxin? – the lipid A portion of lipopolysaccharide (LPS) Fever - elevated body temperature  Vasodilation (leading to shock)  Inflammation  can even result in death  Exotoxins These are substances released from bacteria that damage host tissues.  Cytotoxins - cause damage to cells – Erythrogenic toxins – (S. pyogenes)  damage cells lining capillaries and cause blood to leak out under the skin (scarlet fever). Exotoxins  Enterotoxins - cause damage to the gastrointestinal tract – diarrhea and vomiting – Caused by electrolyte loss (resulting in water loss into the large intestine) Cholera and some E. coli infections (traveler’s diarrhea) – Figure 19-3 B  staphylococcal food poisoning  Exotoxins (cont.) – Some enterotoxins also kill the cells lining the intestines causing dysentery (bloody diarrhea)  bacterial dysentery (Shigella) and E. coli O157:H7 infections  Neurotoxins - inhibit the normal functioning of the nervous system – Tetanus toxin (Clostridium tetanii) blocks inhibitory nerve impulses that allow muscles to relax  Lock Jaw Exotoxins (cont.) – Botulinum toxin (Clostridium botulinum) inhibits the functioning of motor neurons causing flaccid paralysis (muscles can’t contract) – 1mg can kill 1,000,000 guinea pigs – Figure 19-3 C  Table 19-3 Superantigens  Superantigens - toxins that stimulate nonspecific activation of T-cells – These then release large amount of cytokines leading to shock – toxic shock syndrome is caused by a superantigen produced by Staphylococcus aureus – can result in death – Figure 19-4
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                            