Module 10
Normal Microbiota of Digestive System
- Esophagus (peristalsis), stomach (pH 2.0), and duodenum (rapid transport): relatively free of microbes
- Tongue and teeth: millions of bacteria, fungi, protozoa in saliva; viridans streptococci are most prevalent (alpha-hemolytic, g(+), adhesins)
- Lower small intestine and colon: 40% fecal mass is bacteria; microbial antagonists (compete with invaders); Bacteroides (-), Lactobacillus (+), Escherichia (-), etc.
- Obese mice: more g(+) help break down indigestible polysaccharides, releasing sugars that can be absorbed
- Lean mice: more g(-) bacteria (bacteroids)
Dental Caries, Gingivitis, and Periodontal Disease
- 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
- 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
- Treatment?- fill cavities if caught early; scaling and antibacterial rinses for gingivitis; prevent with good oral hygiene and fluoridation of water supply
Peptic Ulcers
- What?-abdominal pain; erosion of stomach, small intestine lining
- 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
- 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
- Diagnosis?- x-ray 4 ulcers & confirm in clinical specimens
- Treatment?- antimicrobials, drugs that inhibit stomach acid; eliminating ALL H. pylori increases cancer risk
Bacterial Gastroenteritis
Rank least to most severe
- Least to most severe: (1) Traveler's diarrhea, (2) Salmonellosis, (3) Shigellosis, (4) Campylobacter diarrhea, (5) Antimicrobial diarrhea, (6) Typhoid Fever, and (7) Cholera
- 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
Shigellosis
- Fever, cramps, purulent and bloody diarrhea, nausea/vomiting
- 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
- 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
- Diagnosis?- by symptoms and Shigella in stool
- Treatment?- supportive and possibly anti-microbials
Traveler’s Diarrhea
-
Who?-
E. coli
: microbiota, g(-) bacilli, ferments lactose into
gas, different strains IDed by surface Ag; nausea, vomit,
diarrhea
- Ex: E. coli O157:H7 has shiga-like toxin, T3SS: bloody diarrhea, fatal hemorrhagic colitis, RBC destruction and kidney failure; neutrophils spread throughout body
- 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
- Diagnosis?- signs and symptoms
- Treatment?- fluid and electrolyte replacement, avoid lactose; antidiarrheal drugs can prolong infection by delaying bacterial expulsion from digestive tract
Campylobacter Diarrhea
- What?- 10+ bowel movements/day, sometimes blood
- Who?- Campylobacter jejuni most common cause in US: g(-) with polar flagella; have adhesins, cytotoxins, endotoxins
- 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
- Diagnosis?- signs/symptoms + bacteria in stool
- Treatment?- usually no treatment needed; use proper hygiene after handling raw poultry
Antimicrobial Associated Diarrhea
- What?- many watery, foul-smelling stools; pseudomembranes
- 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
- How?- antimicrobial use can trigger C. diff. o vergrowth = opportunistic; toxins mediate inflammation and lesion formation
- Diagnosis?- based on bacterial toxin in stool (colonoscopy for seeing pseudomembrane helps but not definitive)
- Treatment?- more antimicrobials often required
Cholera
- What?- rice-water stool for 2-3 days; lose up to 1L fluid/hr
- 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
- How?- contaminated water or raw/undercooked seafood
- Diagnosis?- rice-water stool
- Treatment?- supportive care and tetracycline; vaccine only effective short-term; good hygiene
Salmonellosis
- What?- nonbloody diarrhea, nausea/vomit, fever, headache, pain for 1-2 weeks, rash of rose-colored spots may appear
- Who?- Salmonella enteric serotype Enteritidis and Typhimurium; g(-), motile, peritrichous bacilli
- How?- zoonosis through contaminated eggs, poultry, milk, or handling reptiles; attaches to epithelial cell, induces endocytosis, replicated in phagocytic vesicle, kills cells
- Diagnosis?- find Salmonella in stool
- Treatment?- salmonellosis usually self limiting within a week
Typhoid Fever
- What?- High fever, headache, myalgia, stomach pain, lose appetite, rose-colored spots, usually no diarrhea
-
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:
- disrupt mitochondria, inhibit phagocytosis, rearrange cytoskeletons, or induce apoptosis
- 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
- Diagnosis?- find Salmonella in stool
-
Treatment?- drugs; prevent with proper hygiene and
not letting carriers handle food (Typhoid Mary)
Bacterial Food Poisoning
- What?- nausea, vomiting, diarrhea, cramping, <24hrs
- Who?- S. aureus : can have 5 heat-stable enterotoxins (A-E) that stimulate intestinal muscle contractions, trigger nausea, and cause intense vomiting
- How?- outbreaks associated with social fxns
- Diagnosis?- symptoms
- Treatment?- fluid/electrolyte replacement; proper hygiene
Oral Herpes
- What?- cold sores, fever blisters
- Who?- HSV-1 ( Human herpesvirus 1 ): dsDNA enveloped polyhedral capsid; form syncytia in infected cells; latent virus reactivates
- How?- casual contact in childhood
- Diagnosis?- based on lesions
- Treatment?- no cure, topical acyclovir reduces lesion duration
Mumps
- What?- Parotitis (swelling of parotid salivary glands), face pain, fever, headache, and sore throat. Some asymptomatic
- Who?- Mumps Virus: ssRNA(-), enveloped, helical
- How?- unimmunized child contacting infected person or fomite with saliva
- Diagnosis?- Parotitis with recent exposure; serology a option
- Treatment?- supportive care and pain medication; MMR vaccine
Viral Gastroenteritis
- What?- similar to bacterial gastroenteritis
- Who?- Norovirus (ssRNA(+), naked, star-shaped) or Rotavirus (dsRNA, naked, w/glycoprotein spikes)
- How?- fecal-oral, usually in winter (close quarters); 90% nonbacterial GI infections are Norovirus
- Diagnosis?- serological test to determine which virus
- Treatment?- fluid/electrolyte replacement; vaccine for rotavirus
Hepatitis
- What?- jaundice, abdominal pain, fatigue, vomiting, appetite loss; symptoms can occur years after initial infection; host immune response causes most of the liver damage
- 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
- How?- HAV/HEV fecal-oral; HBV/HCV/HDV needles, sex
- Diagnosis?- observation of jaundice, enlarged liver, or fluid in abdomen, plus serological tests to recognize viral Ag
- Treatment?- supportive care; no cures; good hygiene, protected sex, and vaccines for HAV and HBV available
Giardiasis
- What?- often asymptomatic; greasy, frothy, and odorous diarrhea and associated symptoms can last up to a month
- 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
- How?- cyst from contaminated water; hikers/campers higher risk
- Diagnosis?- observe trophozoite or round/oval cysts in stool
- Treatment?- metronidazole (for adults) or furazolidone (for kids); 80% cure rate
Cryptosporidiosis
- What?- severe watery diarrhea for ~two weeks, headache, myalgia, cramping, nausea, fatigue, severe fluid/weight loss
- Who?- Cryptosporidium : motile, banana-shaped apicomplexan; sporozoites form thick-shelled infective oocysts
- How?- contaminated water, oral-fecal; in healthy adults it spontaneously clears within about a month
- Diagnosis?- oocysts in feces
- Treatment?- supportive; nitazoxanide shortens diarrhea time
Amebiasis
- 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
- 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
- How?- contaminated food, water, hands, oral-anal intercourse; majority develop luminal amebiasis (10% population carriers)
- Diagnosis?- observe in stool or intestinal biopsy
- Treatment?- rehydration, anti-amoebic drugs
Tapeworms
- What?- lack own digestive system; usually asymptomatic, may cause nausea, abdominal pain, weight loss, and some diarrhea
- 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
- How?- raw, undercooked pork/beef; places with poor sewage treatment; living in close contact with livestock
- Diagnosis?- proglottids in stool sample
- Treatment?- niclosamide or praziquantel; thoroughly cook meats
Pinworms
- What?- perianal itching, irritability, loss of appetite; ⅓ cases asymptomatic
- Who?- Enterobius : a nematode; female travels to perianal region, deposits eggs at night, returns to colon, eggs dislodged by scratching
- How?- most common parasitic worm in US
- Diagnosis?- identify eggs or adult pinworms
- Treatment?- anthelmintic drugs; use strict personal hygiene, don’t put things in mouth (children)
Normal Microbiota
of the
Urinary and Reproductive Systems
- Urinary Sys: urethra will have Lactobacillus and Staph. ; above urethra should be sterile
- Male reproductive system: above prostate gland sterile
- Female reproductive system: vagina well colonized depending on hormone cycle; with high estrogen Lactobacillus generally keeps it acidic
Bacterial UTIs
- What?- frequent, urgent, painful urine, may be cloudy with foul odor; usually in girls and women
- Who?- enteric g(-) bacteria, usually E. coli: has flagella (movement up urethra) and attachment fimbriae specific for bladder epithelial cells
- How?- self-inoculate fecal bacteria into urethra; usually females
- Diagnosis?- bacteria in urine
- Treatment?- usually resolves w/o treatment; may require drugs
Leptospirosis
- What?- zoonosis; abrupt fever, myalgia, muscle stiffness, and headache; sometimes nausea, vomiting, diarrhea, dry cough
- Who?- Leptospira : g(-) spirochete, aerobic, highly motile; chemotaxic toward hemoglobin, evades Ab-complement activity, and has adhesins
- 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
- Diagnosis?- specific Ab test (doesn’t gram stain well)
- Treatment?- intravenous penicillin for severe, oral drugs otherwise; vaccine available for livestock and pets
Staphylococcal Toxic Shock Syndrome
- What?- sudden onset fever, chills, vomiting, diarrhea, low blood pressure, confusion, severe red rash; shock if untreated (50% mortality rate)
- Who?-strains of S. aureus : exotoxin causes overactive T-cells to trigger mass inflammation; absorption of toxin into blood causes toxic shock
- How?- usually in menstruating females using tampons
- Diagnosis?- by signs/symptoms; a medical emergency
- Treatment?- remove foreign material and antimicrobial drugs; avoid tampons or use less absorbent tampons
Bacterial Vaginosis
- What?- white vaginal discharge with “fishy” odor, no -itis = no inflammation
- Who?- various anaerobic bacteria replacing normal lactobacilli microbiota
- How?- associated w/multiple sexual partners, vaginal douching
- Diagnosis?- signs/symptoms and clue cells
- Treatment?- oral or vaginal metronidazole
Vaginal Candidiasis
- What?- yeast infection; severe itching and burning in vagina
- Who?- Candida albicans
- How?- opportunistic overgrowth by normal microbiota, due to vaginal pH or microbiota changes; can become systemic in immunocompromised; can transmit between people
- Diagnosis?- ID of Candida in presence of symptoms
- Treatment?- azole or fluconazole; avoid
Gonorrhea (the “Clap”)
- What?- men: painful urination and pus-filled discharge; women: often asymptomatic, pelvic inflammatory disease may develop, fertility problems
- 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
- How?- Only affects humans; risk increases w/ frequent sexual encounters
- Diagnosis?- g(-) diplococci in pus from urethra; genetic probes for asymptomatic infections
- Treatment?- broad-spectrum cephalosporins (many resistant strains); no long-term immunity; no vaccine
Syphilis
- 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)
- 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)
- How?- sexual contact; not very contagious; sometimes vertical transmission; abx usually stop it before tertiary syphilis
- Diagnosis?- primary, secondary, and latent with Ab test; tertiary difficult to diagnose
- Treatment?- penicillin for all but tertiary
Chlamydia
- What?- women usually asymptomatic; men painful urination, pus discharge (like gonorrhea); genital lesion and bubo in groin
- Who?- Chlamydia : nonmotile; obligate intracellular; no cell wall, two membranes, g(-); “elementary bodies” are infectious form and “reticulate bodies” are reproductive form;
- 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
- Diagnosis?- chlamydial DNA by PCR
- Treatment?- Abx
Chancroid
- What?- soft chancres (ulcers), painful upon urination in women
- Who?- Haemophilus : small, pleomorphic g(-) bacteria; obligate parasite requires heme and NAD+ from environment; produces toxin that kills epithelial cells
- How?- rare in US, usually acquired during international travel
- Diagnosis?- soft, painful lesion and presence of bacteria
- Treatment?- antimicrobial drugs
Genital Herpes
- What?- small blisters around genitals or rectum
- 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
- Diagnosis?- characteristic lesions
- Treatment?- acyclovir and other antivirals reduce symptoms; condoms often provide little protection
Genital Warts
- What?- warts on genitalia and surrounding area
- Who?- human papillomavirus (HPV): can cause various cancers by integrating DNA
- 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
- Diagnosis?- presence of warts
- Treatment?- can remove warts; vaccine for HPV strain associated with cervical cancer
AIDS
- What?- die of associated opportunistic diseases
- 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
- How?- replication: attach, entry and uncoating, DNA synthesis, integration, synthesis of RNA and proteins, release, assembly and maturation
- Diagnosis?- Ab to HIV indicates HIV but not AIDS; small % individuals long-term non-progressors=latent entire life=no AIDS
- Treatment?- Antiretroviral therapy (ART), cocktail of drugs
Trichomoniasis
- What?- foul-smelling yellow-green vaginal discharge and vaginal irritation, lesions in females. Males usually asymptomatic
- 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
- How?- STD; most common curable STD in women; increases HIV risk
- Diagnosis?- presence in clinical samples
- Treatment?- single dose oral metronidazole; no long-term immunity