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