Chapters 14/15: Bacterial Pathogenesis & epidemiology Dr. Amy Rogers Office Hours: Mondays & Wednesdays 9-10 AM or by request Bacterial pathogenesis How do we catch disease? How do bacteria cause disease? Well-known bacterial pathogens Bacterial pathogenesis From your textbook: even in our worst circumstances we have always been a relatively minor interest of the vast microbial world. Pathogenicity is not the rule. Indeed, it occurs so infrequently and involves such a relatively small number of species, considering the huge population of bacteria on earth, that it has a freakish aspect. Disease usually results from inconclusive negotiations for symbiosis, an overstepping of the line by one side or the other, a biological misinterpretation of borders. Lewis Thomas 1974 (one of the 20 th century s finest science essayists) Host-microbe relationships Microbes & their hosts have evolved relationships over long periods of time Some relationships are extremely complex The microbes evolve to maximize their reproduction Extremely fast-acting lethal infections are not in the bacteria s best interest (no time to spread!) Such infections typically arise suddenly and disappear over time Many microbes that interact with humans are not pathogenic under ordinary circumstances For example, the normal flora: Commensals; opportunistic pathogens Host-microbe relationships Contamination / Colonization: Microbes are present either transiently or stably in a harmless way Infection Microbes are multiplying inappropriately in or on host s body Disease Microbial growth disrupts health or bodily functions Let s talk about infectious disease Pathogenicity: The ability of a microbe to cause disease There are varying degrees of pathogenicity, affected by: Ability to invade the host Ability to multiply within the host Ability to avoid host defenses Examples: Some bacteria will almost always cause disease if they enter a host; others will cause disease rarely, or only if the host is immunocompromised Some bacteria will cause disease only if a large number of bacteria gain entry to the host; others may need as few as 10 cells! 1
Let s talk about infectious disease Virulence: The severity of disease produced by a pathogen Example: Bacillus cereus: mild gastroenteritis; rabies virus: death Not all members of a species are equally virulent Different strains or isolates may exhibit varying degrees of virulence» Avery s rough & smooth pneumococci Early in an epidemic, a pathogen s virulence may increase as it rapidly passes from one host to the next (e.g., influenza) Virulence Attenuation: Decreased virulence The disease-producing ability of a pathogen can be weakened. Attenuated strains can be used as vaccines (e.g., rabies). Repeated passage or culturing of a microbe on laboratory media, or in laboratory animals, can produce an attenuated strain How do bacteria cause disease? 1. Access 2. Attachment 3. Colonization 4. Invasion 5. Damage 1. Access How do bacteria enter the body? Penetrate the skin or mucous membranes Sexual transmission With food Inhalation During birth With blood During surgery, or with indwelling medical devices (catheters, heart valves) Entry by inhalation: Bacterial pneumonia Streptococcus pneumoniae: (formerly called pneumococcus) #1 cause of bacterial pneumonia (infection of the lungs) all Streptococci: Gram + catalase -- Nowadays, Streptococcal pneumonia kills mostly older, debilitated people. Standard infant immunization now includes pneumococcal vaccine. S. pneumoniae also causes meningitis Entry by inhalation: Bacterial Meningitis 3 major causes (etiologic agents): Streptococcus pneumoniae Haemophilus influenzae b Neisseria meningitidis Meningitis: inflammation of the meninges (lining surrounding the brain & spinal cord). Symptoms: Nonspecific malaise; then headache, stiff neck, confusion, vomiting, coma, death Note that some viruses can also cause meningitis; generally a less severe disease 2
Bacterial meningitis: Hib H. influenzae b (Hib) primarily causes meningitis in infants #1 cause of mental retardation in U.S. Like S. pneumoniae, a vaccine is now in use Dramatic reductions (>95%) in the # of cases Bacterial meningitis: Neisseria Neisseria meningitidis: Since Hib vaccine introduced, Neisseria now is #1 cause Bacterial meningitis found in military camps, schools. Spread by respiratory droplets but close contact required. Disease progresses very rapidly (death can occur in less than one day!) Vaccine (for some strains) is available, recommended for college freshmen living in dorms Entry during birth: Group B Streptococci Entry with food: Salmonella food poisoning Group B Strep species cause disease in newborns; infection acquired during birth In adults, temporary colonization by group B strep is normal and does NOT lead to disease Pregnant women are tested for vaginal colonization by group B Strep during the last few weeks of pregnancy If positive, mother may get antibiotics during labor to prevent transmission of bacteria to baby Salmonella: factory-raised poultry; eggs; raw milk. Bacteria multiply very rapidly in warm food (reheated, or left on the buffet too long ) They do NOT change taste or appearance of food Wash food preparation areas after touching raw chicken! Also can get Salmonella from skin of pet reptiles 2. Attachment When bacteria enter the body, they may be immediately swept out by urination, coughing or sneezing, bleeding, etc. In order to initiate infection, the bacteria must attach to the host s cell surfaces. Adhesion molecules (on attachment pili, on capsules) are crucial virulence factors for some bacteria. Adhesion molecules allow attachment to receptors on specific cell membranes. Neisseria gonorrohoeae Gram cocci Gonorrhea Adhesins on attachment pili are a critical virulence factor Transmitted by sexual contact Infection can be asymptomatic, especially in women Asymptomatic infections don t get treated, get spread around instead Bacteria can migrate up the Fallopian tubes to cause pelvic inflammatory disease & infertility 3
3. Colonization Attachment alone does not cause infection. Bacteria must be able to survive and multiply at that location. Bacteria must: Tolerate physical conditions presence or absence of oxygen; dry or wet; ph; etc. Escape body defenses sweeping movement of cilia in the lungs, peristalsis in the gut; antimicrobial secretions like lysozyme, digestive enzymes; etc. Helicobacter pylori Bacteria that colonize the stomach Discovered in the 1980 s Previously it was thought the stomach was sterile due to extremely low ph Colonization causes peptic ulcers (stomach/duodenal ulcers) Peptic ulcers used to be a major medical problem (pain, bleeding, progression to stomach cancer) Helicobacter pylori Before H. pylori, ulcers were thought to be a result of excessive acid production Treatment: diet modification (avoid spicy food); acid suppression (antacids, Tagamet, Pepcid, Prilosec); minimize stress Now ulcers can be cured by eliminating H. pylori colonization PeptoBismol + antibiotics 4. Invasion Only a few pathogens cause disease by colonizing surfaces. The rest invade into deeper tissues. Various virulence factors make invasion possible. Hyaluronidase ( spreading factor ) Production of this enzyme is a major virulence factor; it digests hyaluronic acid, a gluelike substance that hold the cells of certain tissues together Invasion using hyaluronidase Invasion: Group A Streptococci All streptococci are Gram +, catalase Many species are part of the normal flora (but not Group A) Group A strep: pathogenic strep Streptococcus pyogenes Strep throat (sore throat, fever, headache) Epithelial cells line body spaces which communicate with the outside Hyaluronidase, β hemolysins (β hemolytic strep), other virulence factors 4
Strep throat Group A Streptococci Cause a wide variety of diseases Skin, wound, burn infections Depends on bacteria getting access Childbed fever (post partum infection) This highly contagious, often deadly infection was a major cause of maternal mortality before doctors paid attention to hygiene (handwashing!) 5. Damage Invasion itself is damaging and can be disease-causing. However, many pathogens produce additional molecules that contribute to virulence (disease severity). Examples: Coagulase Streptokinase Toxins Coagulase (Staphylococcus aureus): clots blood, protects the bacteria from the immune system; but also prevents spread of the bacteria Streptokinase: bacterial enzyme that dissolves blood clots, allowing bacteria to spread Streptokinase can be used as treatment for heart attacks (it will dissolve clots in the coronary arteries) Toxins Some bacteria produce toxins (poisons) Exotoxins: soluble substances secreted out of the bacteria & into the host. Endotoxin: part of the cell wall of Gram negative bacteria; released when bacteria die or divide LPS (lipopolysaccharide) Toxic effects are systemic and nonspecific (fever, low blood pressure) Compared to many exotoxins, endotoxins are relatively weak (takes a lot more endotoxin to cause disease) Exotoxins Extremely potent (tiny doses have severe effects) Most are destroyed by heat Highly specific (each one has a very specific toxic effect) Can immunize against exotoxins Examples: tetanus; botulism (botox); α and β hemolysins; cholera toxin 5
Exotoxins Special terms: Enterotoxin: an exotoxin that acts on the gut Neurotoxin: an exotoxin that acts on the nervous system Toxoid: an exotoxin that has been altered to lose its toxicity, but retains its ability to stimulate an immune response (antigenicity). Toxoids are used in some immunizations (tetanus shot) Exotoxins: Cholera Vibrio cholera Diarrheal disease spread by fecal/oral route (poor sanitation, contaminated water) Bacteria do not invade the intestinal mucosa (wall) but secrete a potent enterotoxin Causes massive (liters) secretion of electrolytes & water from the intestines (secretory diarrhea); death by dehydration within hours Simple oral rehydration therapy (sugar & salts in water) saves lives Intoxications Some bacterial diseases occur without bacteria colonizing the body at all! These intoxications occur when a preformed bacterial exotoxin enters the body and causes damage/disease Classic example: food poisoning Food poisoning: Intoxications Staphylococcal food poisoning: Not an infection (bacteria do not colonize) Staph in unrefrigerated food (e.g., potato salad) multiply and produce enterotoxin People eat the food & quickly (a few hours) get diarrhea, cramps, etc. Note that Staphylococcus aureus can also cause a variety of severe tissue infections, esp. of skin & wounds A variety of exotoxins contribute to Staph virulence Food poisoning: Intoxications: Botulism Clostridium botulinum Produces potent neurotoxin in anaerobic environment (canned foods) Likes alkaline environment of most canned vegetables (green beans, mushrooms); won t grow in acid foods (canned fruit) Destroyed by boiling food prior to eating Intoxications: Botox Because the botulism toxin produces paralysis, now used for cosmetic purposes Inject small dose into muscles of face to release wrinkles Paralysis is reversible (slowly) so must repeat over weeks to months Botulism toxin causes muscle paralysis 6
Other toxic Clostridia: Tetanus All Clostridia species are obligate anaerobes & sporeformers Clostridium tetani infects deep puncture wounds (anaerobic) releases tiny amount of exceedingly potent neurotoxin Tetanus toxin enters nerves, causes muscles to contract ( lockjaw ) Causes slow, gruesome death Can successfully immunize after infection Disease process is slow enough to give tetanus toxoid injection after you step on that rusty nail C. tetani Lockjaw Other Damage: immune-mediated Some disease resulting from bacterial infection isn t caused by the bacteria, but by the body s immune response Ch. 14: p. 385-390; 393-398; 402-407 Group A streptococci: after the infection has cleared, patient may get rheumatic fever (arthritis, heart disease) because of the immune response. Can be avoided if the original infection is treated with antibiotics (prevents a vigorous immune response). 7