Chapter 26: Microbial Diseases

1. Chapter 26: Microbial Diseases

2. Characterizing Microbial Diseases Microbial diseases may be classified based on several criteria: - By organism - By organ system - By route of infection or portal of entry (respiratory tract, gastrointestinal tract, genitourinary tract, conjunctiva, skin and mucous)

3. Characterizing Microbial Diseases • Pathogens can be divided into four main groups based on their route of infection: • Food-borne • Airborne • Bood-borne • Sexually transmitted

4. Many infectious diseases display similar symptoms, making diagnosis difficult. knowledge of a patient’s history sometimes helps with proper diagnosis. Travel information – Diarrheal disease Hobbies – Hunters and tularemia (Francisella tularensis) Occupation – Farmers and Q fever (Coxiella burnetti) Both tularemia and Q fever are zoonotic diseases. ZOONOTIC DISEASESare caused by infectious agents that can be transmitted between (or are shared by) animals and humans

5. Skin and Soft-Tissue Infections Skin infections can range from a simple Boil to a sever form called “flesh-eating disease”. Normal skin microbiota usually protects infections. But people with diabetes and immunesuppressive problems can quickly get skin infections, even with a minor cut. Skin infections are usually caused by G+ organisms such as Staphlyococcus sp.

6. Staphylococcus aureus (normal skin in habitant) - Boils: Organism has coagulase, produces fibrin that protects the organism from antibiotics & host immune system - Can produce toxic shock syndrome toxin (superantigens) - MRSA: Methicillin-resistant S. aureus - Major cause of nosocomial infections (in hospitals) - Some strains make exfoliative toxin (scalded skin syndrome). Skin and Soft-Tissue Infections

8. Streptococcus pyogenes - Best known for causing sore throats and immunological sequelae, such as rheumatic fever - Also necrotizing fasciitis (“flesh-eating” disease) - Many prophages on organisms genome carry virulence factors. Skin and Soft-Tissue Infections

9. Streptococcus pyogenes, Staphylococcus aureus, Vibrio vulnificus, Clostridium perfringens, Bacteroides fragilis. Such infections are more likely to occur in people with compromised immune systems, diabetes, alcoholism/drugs.

10. Table 26-1 Common infectious diseases of the skin.

11. Viruses cause a maculopapular skin rash (a flat, red area on the skin that is covered with small confluent bumps). - Usually infects through respiratory tract - Paramyxovirus: Rubeola (“measles”) - Herpes virus: Chickenpox, shingles - Togavirus: Rubella (“German measles”) Skin and Soft-Tissue Infections

12. Respiratory Tract Infections • Most frequently traveled portal of entry • Common diseases: common cold, measles, tuberculosis, influenza, smallpox, and pneumonia

13. The mucociliary escalator is primary defense. - Bordetella pertussis (cause of whooping cough) inhibits it by binding to lung cilia. Respiratory Tract Infections

14. Pneumonia is caused by many different bacteria Polymorphonuclear leukcytes (PMN) Pneumococcus pneumonia occurs mostly among elderly, immunocompramised individuals such as smokers, diabetes, and alcoholics.

15. Pneumonia • Pneumonia is a disease, not specific infection. • - Caused by many different microbes • - Streptococcus pneumoniaeis the main bacterium: • Has thick capsule that prevents phagocytosis • Can invade the bloodstream (bacteremia) and the covering of the brain (meningitis) • Many S. pneumoniae (30% strains) are resistant to penicillin.

16. Table 26-2 Selected microbes that cause respiratory tract diseases.

17. Table 26-2 Selected microbes that cause respiratory tract diseases (continued).

18. Blastomyces dermatitidis - Dimorphic fungus - Found in the soil - Infection usually associated with occupational and recreational activities - Does not usually cause an increase in WBCs - Can cause metastatic lesions Respiratory Tract Infections

19. Dimorphic fungi can have two morphologies- filamentous (hyphal) or as sperical (yeast). Portal of entry is the respiratory tract.

20. Mycobacterium tuberculosis - An acid-fast bacillus - An ancient and reemerging pathogen - Forms calcified tubercles in the lung - Can disseminate through the bloodstream - Has high mortality rate due to multidrug resistant strains and high susceptibility of HIV patients Respiratory syncytial virus - Can cause lung disease but rarely disseminates Respiratory Tract Infections

21. Gastrointestinal Tract Infections Diarrhea is characterized by frequent loose bowel movements with abdominal cramps and vomiting. A large amount of water and electrolytes are lost from the cells. Dysentery is the sever form of diarrhea involving blood and mucus. Diarrhea or gastroenteritis is due to inflammation caused by viral, bacterial, protozoal, or toxins.

22. Gastroenteritis is caused by many organisms Among bacteria, Shigella, E.coli, Vibrio cholera, Salmonella enterica, and Camphylobacter cause diarrhea Staphylococcus aureus causes food poisoning (not an infection) Eukaryotes: Entamoeba histolytica, Giardia lamblia, Cryptosporidium cause amebic dysentery. Most diarrheal diseases are viral such as Norovirus, Norwalk virus, and Rotavirus.

23. Most gastroenteritis is caused by viruses. Rotaviruses (dsRNAreovirus) - Highly infectious -Can cause lethal dehydration Antibiotics ineffective on viruses Some gastroenteritis resolve themselve In some cases treating with antibiotic triggers the diarreah For example: antibiotic, clindamycin kills normal microbiota, except naturally resistant Clostridium difficile that causes gastrointestinal disease! Gastrointestinal Tract Infections

24. Gastrointestinal Tract Infections • Enterobacterial toxin-producing • strains • Inject toxin via Type III secretion • Bacteria invade epithelial mucosa (considered intracellular pathogens). • -Salmonella, Shigella, enteroinvasiveE. coli (EIEC) • -EIEC and Shigella produce Shiga toxin. • - Blocks host protein synthesis, damages endothelia • - Capillary damage, loss of blood, clots Intracellular pathogen

25. Gastrointestinal Tract Infections • Bacteria remaining outside epithelial cells (considered not intracellular pathogens) • -E. coli: EHEC (O157:H7), ETEC, EAEC • - Entero-hemorrhagic, -toxigenic, -aggregative • - O157=serotype of LPS; H7=serotype of flagella Attachment of E.coli O157:H7 to intestinal cell wall

26. Gastrointestinal Tract Infections • Other bacterial agents of disease • Campylobacter jejuni • - Most frequent bacterial cause of diarrhea • Vibriocholerae = Cholera • S. aureus food poisoning • Secreted toxin is cause without infection. • Protozoa major cause of diarrheal desease • -Entamoebahistolytica, Cryptosporidium parvum, Giardialamblia

27. For many years, formation of gastric ulcers was blamed on eating spicy food and stress. In 1980, Robin Warren and Barry Marshal discovered that Helicobacter pylori as the causative agent of peptic ulcer. Received a Nobel Prize in 2005. • Helicobacter pylori = Gastric ulcers • - Secretes urease: urea → NH4+ • - Neutralizes stomach acid • - Burrows into protective mucous layer

28. The urinary tract includes the kidneys, ureters, urinary bladder, and urethra. - Active infection of the urinary tract occurs in one of three basic ways: - Descending infection from the kidneys - Ascending infection to the kidney - Infection from the urethra to the bladder Most UTIs are caused by Gram-negative rods from the GI tract. - Only 5% are caused by Gram-positive bacteria and fungi. Genitourinary Tract Infections

29. Schematic representation of pathways of renal infection

30. Uropathogenic strains of E. coli (UPEC) - Causes about 75% of UTIs - Invade the bladder up from the urethra - Have P-type pili, with a terminal receptor for the P antigen - Have five unique pathogenicity islands Genitourinary Tract Infections

31. Sexually Transmitted Diseases Syphilis - Caused by the spirochete Treponema pallidum - Primary syphilis: Chancre at site of infection - Secondary syphilis: Generalized rash - Tertiary syphilis: Effects on heart and CNS lips penis vulva cervix vagina tongue Primary syphilis

32. Sexually Transmitted Diseases Chlamydia - Most frequently reported STD in U.S. - Caused by unusual Gram-negative bacteria - Chlamydia trachomatis - Chlamydia pneumoniae - Obligate intracellular pathogens - Both cause STDs, as well as pneumonia and trachoma of the eye. Figure 26.12

33. Sexually Transmitted Diseases Gonorrhea - Caused by the Gram-negative diplococcus Neisseria gonorrhoeae - Most infected men exhibit symptoms, while most women are asymptomatic. - Binds to CD4+ T cells, inhibiting T-cell activation Figure 26.13

34. Sexually Transmitted Diseases • Acquired Immunodeficiency Syndrome • - HIV: A lentiviral retrovirus • - Attacks CD4+ T cells, glial cells • - First stage: AIDS-related complex • - Fever, headache, rash • - Second stage—AIDS • - Depletion of T cells • - Opportunistic infections • - Oral candidiasis • - Pneumocystosis • - Third stage: AIDS-related dementia • - Fourth stage: Rare cancers • - Kaposi’s sarcoma via herpes virus type 8 infection Figure 26.14

35. Sexually Transmitted Diseases Trichomoniasis - ~ 2–3 million infections per year in the U.S. - Caused by Trichomonas vaginalis, a flagellated protozoan - No cyst; transmitted via trophozoite stage - Feeds on bacteria in the vagina - pH increases - Treated with metronidazole

36. Malaria • Most devastating infectious disease known • - Causes 1–3 million deaths per year • - Four protozoan Plasmodium species • - P. falciparum is the most deadly. • - Infect liver, red blood cells (RBCs) • - New merozoites are released every 48–72 hours. • - Many parasites are killed in each generation. • - Others switch protein placed on RBC surface. • - 60 var genes encode different surface proteins. • - It constantly eludes immune system.

37. Malaria: cycle of Plasmodium falciparum transmission between mosquito and human.

38. Figure 26.22A & B Schizont releases merozoites from lysed RBC

39. Systemic Infections • Septicemia disseminating throughout body • Plague • - Bacterium Yersinia pestis • - Bite of flea introduces organism. • - Moves to lymph nodes = Bubonic plague • - Moves to bloodstream = Septicemic plague • - Inhaled = Pneumonic plague • - Highly infectious • - Virulence factors inhibit phagocytosis. • - Type III secretion system injects proteins.

40. Figure 26.23

41. Figure 26.24

42. Systemic Infections • Lyme Disease • - Caused by Borrelia burgdorferi,a spirochete • - Transmitted by ticks • - Bacterium can travel to any part of the body. • - Has three stages: • - Stage 1: A bull’s-eye rash (erythema migrans) • - Stage 2: Joint, muscle, and nerve pain • - Stage 3: Arthritis, with WBCs in the joint fluid • - Treatment with antibiotics is recommended for all stages.

43. Figure 26.25

44. Systemic Infections • Other bacterial infections • - Rickettsia prowazekii – Epidemic typhus • - Salmonella typhi– Typhoid fever • - Francisella tularensis– Tularemia • Blood-borne viruses • - HAV: Hepatitis A – picornavirus (ssRNA) • - HBV: Hepatitis B – hepadnavirus (dsDNA) • - HCV: Hepatitis C – flavivirus (ssRNA) • - All three cause liver infections.