Enteropathogens & Gram- Rods [Part I] (Kirn) - 4/27/16 Flashcards
What are the major GI related bacterial categories and their characteristics?
- Enterobacteriaceae:
- Short thick rods
- Peritrichous flagella
- Oxidase negative - Vibro (closely-related)
- Curved rods, polar flagella
- Oxidase positive - Campylobacter, Helicobacter
- Curved or spiral shape
- Not closely-related to other enteric bacteria
What is the epidemiology of infectious enteropathogens?
Habitat: Intestine
Spread: Oral-Fecal transmission
Classic “Four F’s” - Feces, Fingers, Flies, and Food (and water)
What are the intestinal defense that bacteria must overcome (5)?
- Gastric acid (kills many bacteria)
- Intestinal motility (removes bacteria; anti-motility drugs may prolong illness)
- Normal flora (blocks colonization by pathogens)
- Mucosal immunity (IgA)
- Inflammation (Phagocytes, complement)
What is serotyping?
- Antigens: H (Flagella), O (LPS), K (‘Kapsule’)
- Epidemiologic tool to survey - different serological types differ in virulence (vibrio cholerae, salmonella, E. coli)
What are the three types of intestinal infections (gastroenteritis)?
- Non-inflammatory: bacteria in lumen
- watery diarrhea; no white blood cells in feces; no fever
- virulence factors: adhesions, exotoxins (exotoxin = toxin deliberately secreted, vs. endotoxin, i.e. LPS layer of gram negative organisms)
- exotoxins stimulate salt transport CTFR (pump chloride into lumen… water follows it –> massive diarrhea - up to 20L stool per day)
- Vibrio cholerae, toxin-producing E. coli –> virulence: toxin coregulated pilus - Inflammatory: bacteria INVADE wall
- Diarrhea, often bloody; wbc in feces; fever
- virulence factors: adhesions, cytotoxins, cell invasion (invade and kill enterocytes –> induce their own phagocytosis via Type III system)
- Diarrhea from local production of inflammatory mediators by enterocytes and neutrophils
- Prototypic examples: Shigella (only affects humans.. transfer is from person to person), Salmonella, invasive E. coli, Campylobacter - Penetrating: bacteria BEYOND wall
E. coli that cause diarrhea - three types with different virulence factors
- Enterotoxigenic E. coli [ETEC]
- Most adults immune to local ETEC
- NOT immune to ETEC elsewhere
- Most common cause of ‘Traveler’s diarrhea’
- Adhere to intestinal mucosa via pili
- Two exotoxins, distinguished by heat sensitivity
- Disease is a little less severe than what we see for cholera toxin
- Enteropathogenic E. coli [EPEC]
- Adhere to surface of enterocytes
- Utilizes Type III secretion system (basically like a syringe) - injects proteins into cytosol –> cytoskeletal rearrangement
- Brush border disappears (“attaching and effacing lesion”)
- ‘Pedestal’ that cups bacterium produced - Shiga toxin producing E. coli [STEC]
- EPEC that produces Shiga-like toxin (SLT)
- Also referred to as enterohemorrhagic E. coli (EHEC)
- So has EHEC properties + produces Shiga toxin
- Predominant serotype: O157:H7
- Principal host of O157:H7 is cattle
- Outbreaks from fecal contamination of hamburgers (grinding), apple cider, water
What is Shigella? Characteristics? Mechanism of infection?
Bacillary dysentery characterized by:
- Frequent, painful , low-volume stools containing blood, wbc, mucus; abdominal cramps
- Four ‘species’ defined by O-antigen
1) S. dysenteriae (most virulent, least common)
2) S. flexneri
3) S. boydii
4) S. sonnei (least virulent, most common)
Mechanism of infection:
- Transcytosis by M cells (invade and kill cells of intestinal mucosa)
- Invade enterocytes via basolateral surface –> induce phagocytosis by Type III system –> Lyse phagocytic vacuole –> bacteria enter cytosol –> proteins on bacterial surface induce actin polymerization –> Actin ‘tail’ pushes bacteria through plasma membrane into adjacent cells
Shiga toxin:
- A subunit of AB5 structure cleaves RNA of large ribosomal subunit at specific position, inactivating ribosome
- Isolates w/o toxin produce dysentery but less severe
- Major role of toxin is systemic: Hemolytic-uremic syndrome (HUS)–microvascular damage in kidney, red cell lysis
Non-typhoidal Salmonella
- Human infections mostly from meat, eggs
- Causes Gastroenteritis (=Enterocolitis)
- Exit lumen via M cells, invade enterocytes, multiply locally
- Induce apoptosis in macrophages via Type III system
- Non-bloody diarrhea, fever, nausea, vomiting
Campylobacter jejuni (campy = curved)
- Wide spectrum of disease
- “Gullwing” morphology on gram stain
- Cytotoxin
- Common, not recognized until recently, transmitted from contaminated food (chicken)
- Poor growth on media used for recovery of intestinal pathogens
Helicobacter and peptic ulcers
Treatment: surgery, stress relief, antacids
Now it is clear that H. pylori is not only associated with peptic ulcers but also MALT lymphoma
H. pylori escapes stomach acid:
- Resides below mucus layer
- Urease converts urea to ammonia (basic)
- Pathogenic strains: Type IV secretion system exports cytotoxin
- Chronic infection/inflammation: stomach cancer, gastric lymphoma
Diagnosis:
- Gastric biopsy
- ‘Breath test’ - patients ingest 14C or 13C-urea (urease convrts urea to ammona + CO2) –> measure exhaled CO2
- Stool antigen assays
Treatment: antibiotics + bismuth salt [pepto-bismol] + H+ pump inhibitor to reduce gastric acid, speed healing
What is penetrating disease?
- Early: +/- diarrhea (bacteria in small intestine)
- Later: Systemic febrile illness (bacteria invade/exit large intestine)
- Virulence factors: adhesins, cell invasion, inhibition/killing of phagocytes
- Invade intestinal wall, spread: 1) to local lymph nodes (Yersinia), and 2) systemically (typhoidal Salmonella)
Penetrating = Enteropathogenic Yersinia:
- Y. enterocolitica
- Y. pseudotuberculosis
Intestine –> local lymph nodes
Type III system translocates proteins that inhibit phagocytosis
Painful inflammation of lymph nodes, may mimic appendicitis
Grow at 4 degrees Celsius (refrigerated foods: milk, blood products, etc…)
Penetrating = Typhoidal Salmonella
S. Typhi unique to humans*
Capsule = Vi (virulence) antigen (characteristic of S. Typhi)*
Penetrate intestine via M cells
Do not cause macrophage apoptosis
Multiply inside phagocytic vacuole
Spread throughout body
May be cultured from bone marrow
Can establish chronic carrier state in gall bladder (scars, stones pre-dispose)
Carrier can shed Salmonella for years
What are the four major categories of Extra-Intestinal Infections?
- UTI
- Septicemia and Meningitis
- Nosocomial [Hospital-Acquired] Infections
- Opportunistic infections
UTI
- E. coli: >80% of uncomplicated UTI
- Cystitis [infection of bladder]: urgency, frequency, dysuria
- Pyelonephritis [infection of kidney]: P-fimbrae–bacteria adhere to UT epithelium
