Module 10

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Microbiology
Chapters 23, 24
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1

Normal Microbiota of Digestive System

  1. Esophagus (peristalsis), stomach (pH 2.0), and duodenum (rapid transport): relatively free of microbes
  2. Tongue and teeth: millions of bacteria, fungi, protozoa in saliva; viridans streptococci are most prevalent (alpha-hemolytic, g(+), adhesins)
  3. Lower small intestine and colon: 40% fecal mass is bacteria; microbial antagonists (compete with invaders); Bacteroides (-), Lactobacillus (+), Escherichia (-), etc.
    1. Obese mice: more g(+) help break down indigestible polysaccharides, releasing sugars that can be absorbed
    2. Lean mice: more g(-) bacteria (bacteroids)
2

Dental Caries, Gingivitis, and Periodontal Disease

  1. What?- caries= cavities; periodontal disease = inflammation, infection of tissues surrounding/ supporting the teeth; gingivitis= inflammation of gums (swollen, bright red, and/or bleeding), a type of periodontal disease
  2. Who?- Strep. mutans : causes caries; dextran and adhesion factors allow biofilm formation on teeth = plaque; plaque bacteria ferment sugars to acids that dissolve enamel; when calcium salts mineralize plague = tartar; tartar trapped at base of tooth triggers periodontal disease
  3. Treatment?- fill cavities if caught early; scaling and antibacterial rinses for gingivitis; prevent with good oral hygiene and fluoridation of water supply
3

Peptic Ulcers

  1. What?-abdominal pain; erosion of stomach, small intestine lining
  2. Who?- Helicobacter pylori : g(-), helical, highly mobile; inhibits acid production by stomach, flagella helps burrowing, adhesins help attachment to gastric cells, urease neutralizes acid; enzymes inhibit phagocytic killing
  3. How?- Burrows into stomach lining, attaches to cell membrane, triggers inflammation & epithelial destruction with toxins & leaking gastric acid; gastric acid destroys underlying tissue = ulcer. Stress, non-steroidal anti-inflammatories (aspirin, ibuprofen, etc), alcoholism, smoking increase symptoms
  4. Diagnosis?- x-ray 4 ulcers & confirm in clinical specimens
  5. Treatment?- antimicrobials, drugs that inhibit stomach acid; eliminating ALL H. pylori increases cancer risk
4

Bacterial Gastroenteritis

Rank least to most severe

  1. Least to most severe: (1) Traveler's diarrhea, (2) Salmonellosis, (3) Shigellosis, (4) Campylobacter diarrhea, (5) Antimicrobial diarrhea, (6) Typhoid Fever, and (7) Cholera
  2. What?- inflammation of stomach or intestines (usually causing diarrhea); nausea, vomiting, diarrhea, loss of appetite, abdominal pain, and cramps; severe type is dysentery: loose frequent stools, w/ mucus and blood
5

Shigellosis

  1. Fever, cramps, purulent and bloody diarrhea, nausea/vomiting
  2. Who?- Shigella : nonmotile g(-) bacillus; virulence: T3SS and Shiga toxin, an enterotoxin that binds cells, triggers loss of electrolytes and water, and can stop host protein synthesis
  3. How?- fecal contamination; person-to-person, colonizes small then large intestine (main infection); in large intestine binds epithelia, triggers endocytosis, replicates in cytosol, uses actin comet-tail to invade neighbor cells, forms mucosal abscess as cells are killed by infection, may invade bloodstream but quickly phagocytized and killed = no bacteremia
  4. Diagnosis?- by symptoms and Shigella in stool
  5. Treatment?- supportive and possibly anti-microbials
6

Traveler’s Diarrhea

  1. Who?- E. coli : microbiota, g(-) bacilli, ferments lactose into gas, different strains IDed by surface Ag; nausea, vomit, diarrhea
    1. Ex: E. coli O157:H7 has shiga-like toxin, T3SS: bloody diarrhea, fatal hemorrhagic colitis, RBC destruction and kidney failure; neutrophils spread throughout body
  2. How?- in water with poor sanitation; diarrhea by enterotoxin causing electrolyte loss; causes disease when in upper digestive system instead of lower gut; contaminated milk, juice, ground beef for O157:H7
  3. Diagnosis?- signs and symptoms
  4. Treatment?- fluid and electrolyte replacement, avoid lactose; antidiarrheal drugs can prolong infection by delaying bacterial expulsion from digestive tract
7

Campylobacter Diarrhea

  1. What?- 10+ bowel movements/day, sometimes blood
  2. Who?- Campylobacter jejuni most common cause in US: g(-) with polar flagella; have adhesins, cytotoxins, endotoxins
  3. How?- zoonotic from poultry, other mammals; survives in cells when endocytosed; non-motile mutants are avirulent; invade J, I, and colon causing bleeding lesions and inflammation
  4. Diagnosis?- signs/symptoms + bacteria in stool
  5. Treatment?- usually no treatment needed; use proper hygiene after handling raw poultry
8

Antimicrobial Associated Diarrhea

  1. What?- many watery, foul-smelling stools; pseudomembranes
  2. Who?- Clostridium difficile : g(+), anaerobic bacillus, can be normal microbiota; two toxins, A and B: toxin A breaks tight junctions b/w epithelial cells causing inflammation and fluid loss, while toxin B is cytotoxic and causes lesions
  3. How?- antimicrobial use can trigger C. diff. o vergrowth = opportunistic; toxins mediate inflammation and lesion formation
  4. Diagnosis?- based on bacterial toxin in stool (colonoscopy for seeing pseudomembrane helps but not definitive)
  5. Treatment?- more antimicrobials often required
9

Cholera

  1. What?- rice-water stool for 2-3 days; lose up to 1L fluid/hr
  2. Who?- Vibrio cholerae : g(-) w/polar flagella; normally found in salt water; Cholera toxin (enterotoxin) subunit A1 enters epithelial cell, activates adenylate cyclase to convert ATP to cAMP, this causes cell to secrete electrolytes into intestinal lumen, water follows into lumen = diarrhea; high infective dose due to lack of acid resistance genes
  3. How?- contaminated water or raw/undercooked seafood
  4. Diagnosis?- rice-water stool
  5. Treatment?- supportive care and tetracycline; vaccine only effective short-term; good hygiene
10

Salmonellosis

  1. What?- nonbloody diarrhea, nausea/vomit, fever, headache, pain for 1-2 weeks, rash of rose-colored spots may appear
  2. Who?- Salmonella enteric serotype Enteritidis and Typhimurium; g(-), motile, peritrichous bacilli
  3. How?- zoonosis through contaminated eggs, poultry, milk, or handling reptiles; attaches to epithelial cell, induces endocytosis, replicated in phagocytic vesicle, kills cells
  4. Diagnosis?- find Salmonella in stool
  5. Treatment?- salmonellosis usually self limiting within a week
11

Typhoid Fever

  1. What?- High fever, headache, myalgia, stomach pain, lose appetite, rose-colored spots, usually no diarrhea
  2. Who?- Salmonella enteric serotype Typhi and Paratyphi; g(-), motile, peritrichous bacilli; tolerate stomach acid, pass into small intestines, attach to epithelial cells, and use T3SS to deliver toxins that:
    1. disrupt mitochondria, inhibit phagocytosis, rearrange cytoskeletons, or induce apoptosis
  3. fecal-oral route: typhoid fever from contaminated food and water; can move into bloodstream, cause bacteremia, and be carried by phagocytes to establish semi-permanent infections
  4. Diagnosis?- find Salmonella in stool
  5. Treatment?- drugs; prevent with proper hygiene and not letting carriers handle food (Typhoid Mary)
12

Bacterial Food Poisoning

  1. What?- nausea, vomiting, diarrhea, cramping, <24hrs
  2. Who?- S. aureus : can have 5 heat-stable enterotoxins (A-E) that stimulate intestinal muscle contractions, trigger nausea, and cause intense vomiting
  3. How?- outbreaks associated with social fxns
  4. Diagnosis?- symptoms
  5. Treatment?- fluid/electrolyte replacement; proper hygiene
13

Oral Herpes

  1. What?- cold sores, fever blisters
  2. Who?- HSV-1 ( Human herpesvirus 1 ): dsDNA enveloped polyhedral capsid; form syncytia in infected cells; latent virus reactivates
  3. How?- casual contact in childhood
  4. Diagnosis?- based on lesions
  5. Treatment?- no cure, topical acyclovir reduces lesion duration
14

Mumps

  1. What?- Parotitis (swelling of parotid salivary glands), face pain, fever, headache, and sore throat. Some asymptomatic
  2. Who?- Mumps Virus: ssRNA(-), enveloped, helical
  3. How?- unimmunized child contacting infected person or fomite with saliva
  4. Diagnosis?- Parotitis with recent exposure; serology a option
  5. Treatment?- supportive care and pain medication; MMR vaccine
15

Viral Gastroenteritis

  1. What?- similar to bacterial gastroenteritis
  2. Who?- Norovirus (ssRNA(+), naked, star-shaped) or Rotavirus (dsRNA, naked, w/glycoprotein spikes)
  3. How?- fecal-oral, usually in winter (close quarters); 90% nonbacterial GI infections are Norovirus
  4. Diagnosis?- serological test to determine which virus
  5. Treatment?- fluid/electrolyte replacement; vaccine for rotavirus
16

Hepatitis

  1. What?- jaundice, abdominal pain, fatigue, vomiting, appetite loss; symptoms can occur years after initial infection; host immune response causes most of the liver damage
  2. Who?- different viruses, different genre, all affect liver. Hep A Virus (HAV): survives on surfaces, hard to disinfect, fecal-oral, infectious, mild condition. HBV: Replicates in and released into blood by liver cells. HCV: Lacks replication proofreading, therefore high mutation rate and unable to ever clear infection; very bad HDV: Uses HBV capsid so can only infect people with HBV. HEV: fecal-oral, mild condition
  3. How?- HAV/HEV fecal-oral; HBV/HCV/HDV needles, sex
  4. Diagnosis?- observation of jaundice, enlarged liver, or fluid in abdomen, plus serological tests to recognize viral Ag
  5. Treatment?- supportive care; no cures; good hygiene, protected sex, and vaccines for HAV and HBV available
17

Giardiasis

  1. What?- often asymptomatic; greasy, frothy, and odorous diarrhea and associated symptoms can last up to a month
  2. Who?- Giardia : diplomonad flagellate; motile feeding trophozoite and dormant cyst forms; blocks intestinal absorption so more nutrients for bacteria, causing massive gas; doesn’t invade inside intestinal wall
  3. How?- cyst from contaminated water; hikers/campers higher risk
  4. Diagnosis?- observe trophozoite or round/oval cysts in stool
  5. Treatment?- metronidazole (for adults) or furazolidone (for kids); 80% cure rate
18

Cryptosporidiosis

  1. What?- severe watery diarrhea for ~two weeks, headache, myalgia, cramping, nausea, fatigue, severe fluid/weight loss
  2. Who?- Cryptosporidium : motile, banana-shaped apicomplexan; sporozoites form thick-shelled infective oocysts
  3. How?- contaminated water, oral-fecal; in healthy adults it spontaneously clears within about a month
  4. Diagnosis?- oocysts in feces
  5. Treatment?- supportive; nitazoxanide shortens diarrhea time
19

Amebiasis

  1. What?- Lumenal amebiasis: asymptomatic. Invasive amebic dysentery: severe diarrhea, colitis, appendicitis, bloody mucus-containing stool, pain. Invasive extraintestinal amebiasis: necrotic lesions in various organs, death
  2. Who?- Entamoeba histolytica : infective, resistant, chitin-shelled cysts develop into trophozoites in peritoneal cavity or blood causing symptoms; adhesion proteins, proteases, ion-channel creating proteins, and toxic proteins
  3. How?- contaminated food, water, hands, oral-anal intercourse; majority develop luminal amebiasis (10% population carriers)
  4. Diagnosis?- observe in stool or intestinal biopsy
  5. Treatment?- rehydration, anti-amoebic drugs
20

Tapeworms

  1. What?- lack own digestive system; usually asymptomatic, may cause nausea, abdominal pain, weight loss, and some diarrhea
  2. Who?- Taenia : two species, beef or pork; up to 4m long; eggs/gravid proglottids pass in human stool, consumed by pigs, eggs hatch into larvae, travel to pig muscle and form cysticerci, human ingests raw/undercooked meat, cysticercus excysts, attaches to mucosa of intestine, matures, forms new proglottids
  3. How?- raw, undercooked pork/beef; places with poor sewage treatment; living in close contact with livestock
  4. Diagnosis?- proglottids in stool sample
  5. Treatment?- niclosamide or praziquantel; thoroughly cook meats
21

Pinworms

  1. What?- perianal itching, irritability, loss of appetite; ⅓ cases asymptomatic
  2. Who?- Enterobius : a nematode; female travels to perianal region, deposits eggs at night, returns to colon, eggs dislodged by scratching
  3. How?- most common parasitic worm in US
  4. Diagnosis?- identify eggs or adult pinworms
  5. Treatment?- anthelmintic drugs; use strict personal hygiene, don’t put things in mouth (children)
22

Normal Microbiota

of the

Urinary and Reproductive Systems

  1. Urinary Sys: urethra will have Lactobacillus and Staph. ; above urethra should be sterile
  2. Male reproductive system: above prostate gland sterile
  3. Female reproductive system: vagina well colonized depending on hormone cycle; with high estrogen Lactobacillus generally keeps it acidic
23

Bacterial UTIs

  1. What?- frequent, urgent, painful urine, may be cloudy with foul odor; usually in girls and women
  2. Who?- enteric g(-) bacteria, usually E. coli: has flagella (movement up urethra) and attachment fimbriae specific for bladder epithelial cells
  3. How?- self-inoculate fecal bacteria into urethra; usually females
  4. Diagnosis?- bacteria in urine
  5. Treatment?- usually resolves w/o treatment; may require drugs
24

Leptospirosis

  1. What?- zoonosis; abrupt fever, myalgia, muscle stiffness, and headache; sometimes nausea, vomiting, diarrhea, dry cough
  2. Who?- Leptospira : g(-) spirochete, aerobic, highly motile; chemotaxic toward hemoglobin, evades Ab-complement activity, and has adhesins
  3. How?- via contaminated water and around animals; penetrates mucous membranes or microabrasions, corkscrews into blood then throughout body, eventually bacteremia resolves with only the kidney colonized
  4. Diagnosis?- specific Ab test (doesn’t gram stain well)
  5. Treatment?- intravenous penicillin for severe, oral drugs otherwise; vaccine available for livestock and pets
25

Staphylococcal Toxic Shock Syndrome

  1. What?- sudden onset fever, chills, vomiting, diarrhea, low blood pressure, confusion, severe red rash; shock if untreated (50% mortality rate)
  2. Who?-strains of S. aureus : exotoxin causes overactive T-cells to trigger mass inflammation; absorption of toxin into blood causes toxic shock
  3. How?- usually in menstruating females using tampons
  4. Diagnosis?- by signs/symptoms; a medical emergency
  5. Treatment?- remove foreign material and antimicrobial drugs; avoid tampons or use less absorbent tampons
26

Bacterial Vaginosis

  1. What?- white vaginal discharge with “fishy” odor, no -itis = no inflammation
  2. Who?- various anaerobic bacteria replacing normal lactobacilli microbiota
  3. How?- associated w/multiple sexual partners, vaginal douching
  4. Diagnosis?- signs/symptoms and clue cells
  5. Treatment?- oral or vaginal metronidazole
27

Vaginal Candidiasis

  1. What?- yeast infection; severe itching and burning in vagina
  2. Who?- Candida albicans
  3. How?- opportunistic overgrowth by normal microbiota, due to vaginal pH or microbiota changes; can become systemic in immunocompromised; can transmit between people
  4. Diagnosis?- ID of Candida in presence of symptoms
  5. Treatment?- azole or fluconazole; avoid
28

Gonorrhea (the “Clap”)

  1. What?- men: painful urination and pus-filled discharge; women: often asymptomatic, pelvic inflammatory disease may develop, fertility problems
  2. Who?- Neisseria gonorrhoeae : g(-), often diplococci with polysaccharide capsule and endotoxin; attaches to epithelial cells of mucous membranes, phagocytosed by neutrophils but survives and reproduces within them, traveling around the body; has highly variable surface Ag
  3. How?- Only affects humans; risk increases w/ frequent sexual encounters
  4. Diagnosis?- g(-) diplococci in pus from urethra; genetic probes for asymptomatic infections
  5. Treatment?- broad-spectrum cephalosporins (many resistant strains); no long-term immunity; no vaccine
29

Syphilis

  1. What?- 4 stages: Primary: small, painless, hard, red lesions; VERY infectious. Secondary: sore throat, headache, non-itchy rash. Latent: no symptoms. Tertiary: dementia, blindness, paralysis, heart failure, and gummas (swollen rubbery lesions)
  2. Who?- Treponema : helical, thin spirochete (poor gram-stain, use special silver stain); only lives in people; can’t be pure cultured in lab; has adhesions and glycocalyx (protects from phagocytosis)
  3. How?- sexual contact; not very contagious; sometimes vertical transmission; abx usually stop it before tertiary syphilis
  4. Diagnosis?- primary, secondary, and latent with Ab test; tertiary difficult to diagnose
  5. Treatment?- penicillin for all but tertiary
30

Chlamydia

  1. What?- women usually asymptomatic; men painful urination, pus discharge (like gonorrhea); genital lesion and bubo in groin
  2. Who?- Chlamydia : nonmotile; obligate intracellular; no cell wall, two membranes, g(-); “elementary bodies” are infectious form and “reticulate bodies” are reproductive form;
  3. How?- enters through scrapes and cuts; infects lining of mucous membranes (respiratory, reproductive, anus, or rectum); lesions at infection site often overlooked since small, painless, and quickly healing; most commonly reported STD in US
  4. Diagnosis?- chlamydial DNA by PCR
  5. Treatment?- Abx
31

Chancroid

  1. What?- soft chancres (ulcers), painful upon urination in women
  2. Who?- Haemophilus : small, pleomorphic g(-) bacteria; obligate parasite requires heme and NAD+ from environment; produces toxin that kills epithelial cells
  3. How?- rare in US, usually acquired during international travel
  4. Diagnosis?- soft, painful lesion and presence of bacteria
  5. Treatment?- antimicrobial drugs
32

Genital Herpes

  1. What?- small blisters around genitals or rectum
  2. Who?- Human herpesvirus 2 : dsDNA, polyhedral, enveloped virus; can be latent in nerve cells; attaches and fuses with host cell membrane; kills epithelial cells at infection site; blisters may form away from infection site; vertical transmission possible; asymptomatic can pass virus
  3. Diagnosis?- characteristic lesions
  4. Treatment?- acyclovir and other antivirals reduce symptoms; condoms often provide little protection
33

Genital Warts

  1. What?- warts on genitalia and surrounding area
  2. Who?- human papillomavirus (HPV): can cause various cancers by integrating DNA
  3. How?- invade skin and mucous membranes during sex; 3-4 month incubation; cytotoxic T cells eventually recognize and destroy infected cells so warts disappear over time; most common STD in US
  4. Diagnosis?- presence of warts
  5. Treatment?- can remove warts; vaccine for HPV strain associated with cervical cancer
34

AIDS

  1. What?- die of associated opportunistic diseases
  2. Who?- HIV (retrovirus): ssRNA; HIV-1 common in US and Europe, HIV-2 common in W. Africa; has reverse transcriptase, integrase, tRNA, protease in capsid; enveloped with glycoproteins; attacks CD4+ helper T cells
  3. How?- replication: attach, entry and uncoating, DNA synthesis, integration, synthesis of RNA and proteins, release, assembly and maturation
  4. Diagnosis?- Ab to HIV indicates HIV but not AIDS; small % individuals long-term non-progressors=latent entire life=no AIDS
  5. Treatment?- Antiretroviral therapy (ART), cocktail of drugs
35

Trichomoniasis

  1. What?- foul-smelling yellow-green vaginal discharge and vaginal irritation, lesions in females. Males usually asymptomatic
  2. Who?- Trichomonas : leaf-shaped protozoa with 5 flagella; in humans only; reproduces at pH 5-6, so lactobacilli colonization good with pH 4-4.5; no cysts; don’t survive long in environment
  3. How?- STD; most common curable STD in women; increases HIV risk
  4. Diagnosis?- presence in clinical samples
  5. Treatment?- single dose oral metronidazole; no long-term immunity