Term
| What microenviornmental changes are known to cause coordinate regulation of virulence gene expression? |
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Definition
1) pH
2) Temperature
3) Nutrition (iron)
4) Osmolarity |
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Term
| How do "Two Component Regulatory Systems" generally sense environmental change? |
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Definition
**1 two-component system can regulate another within the same bacteria**
1) Sensor protein- transmembrane protein that undergoes conformational change to activate cytoplasmic Histidine kinase domain
2) Transcriptional regulator- Phosphorylated by activated sensor leading to transcriptional activation/repression of virulence genes |
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Term
| What 2-component system is seen in Salmonella? |
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Definition
PhoP/PhoQ system- necessary for survival
PhoQ is sensor and PhoP is transcriptional regulator
1) when Salmonella enter phagocytes, low Mg activates PhoQ, which phosphorylates PhoP
2) PhoP increases expression of "pag" (intracellular survival) genes and represses "prg" genes (extracellular survival).
3) pag genes give resistance to antimicrobial peptides through PrmA/PrmB system, which causes expression of enzmes that modify LPS to prevent it from binding antimicrobials (also produces protective membrane proteins) |
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Term
| How is Salmonella a good example of one 2-component system regulating another? |
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Definition
1) PhoQ/PhoP is active when bacteria is phagocytosed, leading to expression of pag and repression of prg genes
2) PhoQ/PhoP activation leads to PrmA/PrmB activation, which causes production of enzymes that modify LPS so that is will not bind antimicrobial peptides. |
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Term
| How do "Quorum Sensing Systems" generally sense environmental change? |
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Definition
Method of sensing "pathogen density" in order to adjust virulence factors
1) Production/Secretion of autoinducer in response to proper density leads to activation of transcriptional regulator
2) Transcriptional regulator increases virulence gene expression (theres enough of us, time to do our stuff!) |
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Term
| How does "Quorum Sensing" function in Pseudomonas aeruginosa? |
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Definition
2 different levels of transcriptional regulation
1) Proper bacterial density leads to PAI-1 induction, which activates LASR (transcriptional regulator)
2) LASR activates exoA (Exotoxin A) and PAI-2 (second regulator)
3) PAI-2 activates RhiR
4) RhIR activates vg1 and vg2 (Virulence factors 1 and 2) |
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Term
| How does Cross-talk between Quorum-Sensing and Two-Component Regulatory systems occur in S. aureus? |
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Definition
Autoinducer (AIP) binds and activates sensor of 2-component system (AgrC)
** If this occurs between cells, binding of AIP occurs, but activation DOES NOT, causing decreased toxin expression** |
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Term
A patient presents with dark urine and vomiting, as well as "rose spots" on her stomach.
What is the reservoir/transmission of the pathogen causing these symptoms? |
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Definition
S. typhi (enterobacteria- gram (-), motile rod that is oxidase-negative and facultatively anaerobic.
1) Human reservoir with important human carriers
2) Spread by fecal-oral contamination. |
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Term
| What is the different between reservoir and transmission in nontyphoid salmonella and S. typhi? |
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Definition
Reservoir- Non-typhoid salmonella has zoonotic reservoir in food animals and pets, while S. typhi is only humans
Transmission- Nontyphoid salmonella is acquired by ingestion of food, water, and person-to-person by fecal-oral, while S. typhi is ONLY fecal-oral |
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Term
| What virulence factors are associated with S. typhi? |
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Definition
**SAME AS NON-TYPHOID EXCEPT FOR Vi ANTIGEN)
1) LPS (inflammation)
2) Type III secretion
- Inv/Spa (early entry to intestinal epithelia)
- Spi/Ssa (survival inside macrophages)
3) PhoP/PhoQ (intracellular survival)
4) PagC outer membrane protein to resist antimicrobial peptides
5) Adhesins (fimbrial and afimbrial)
6) Vi antigen: polysacharide capsule
7) Flagella |
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Term
| What virulence factors are associated with non-typhoid Salmonella? |
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Definition
**SAME AS TYPHI, BUT WITHOUT Vi ANTIGEN)
1) LPS (inflammation)
2) Type III secretion
- Inv/Spa (early entry to intestinal epithelia)
- Spi/Ssa (survival inside macrophages)
3) PhoP/PhoQ (intracellular survival)
4) PagC outer membrane protein to resist antimicrobial peptides
5) Adhesins (fimbrial and afimbrial)
6) Flagella |
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Term
| What is the pathogenesis of Non-typhoid Salmonella? |
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Definition
SHORT
1) Ingest to SI epithelium
2) Invade (Inv/Spa) M cells and enterocytes
3) Migrate to basal side in endosomes
4) Enter lamina propria and eaten by macrophages (PhoP/PhoQ)
5) Inlammation (immunocompetent) or Dissemination (AIDS or Sickle Cell)
Explanation
1) After ingestion, bacteria enter SI and adhere to epithelium
2) Invade using Inv/Spa, trigger membrane ruffling, and internalized by M cells and enterocytes
3) Remain in endosomes, which translocate to basal side of cell
4) After contact with basal membrane, Salmonella cell released into Lamina propria, where it is eaten by macrophages (using PhoP/PhoQ to adjust to acid and LPS modifications)
5) In immunocompetent, you get inflammatory response with fever, cramps and diarrhea, but NOT SPREAD
In immunocompromised, dissemination occurs leading to septicemia and death in AIDS patients or children with Sickle Cell (also osteomyelitis). |
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Term
| What is the pathogenesis of Salmonella Typhi? |
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Definition
SHORT
1) Ingest to SI epithelium
2) Invade (Inv/Spa) M cells and enterocytes
3) Migrate to basal side in endosomes
4) Crosses to lamina propria and disseminates to reticuloendothelial tissue
5) Replicate and emerge in blood and bile (full blown Typhoid)
6) Enter intestines via bile, triggering strong inflammatory response leading to hemorrhage, perforation and possibly peritonitis (10-20% mortality without treatment |
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Term
| How does the pathogenesis of S. typhi differ from that of non-typhoid salmonella? |
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Definition
Both begin with ingestion, travel to SI, invasion of M cell and enterocytes, migration to basal side of cell in endosome and entry into lamina propria.
1) At lamina propria, S. typhi quickly disseminates to reticuloendothelial tissue for multiplication and release in blood and bile, after which a secondary infection of intestine causes severe inflammation
2) At lamina propria, non-Typhoid salmonella usually causes local inflammatory response, except in case of AIDS or Sickle Cell, where disseminated disease may be seen (septicemia and maybe death) |
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Term
| Which population is an important carrier population for S. typhi? |
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Definition
| People with gallstones that can shed viable bacteria in their feces and be the source of new infections. |
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Term
| How do you diagnose/treat Salmonella? |
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Definition
- Lactose-negative bacteria on MacConkey and biochemicals
- For nontyphoid use stool culture (or blood if septicemia expected)
- For typhoid Salmonella, use blood cultures before stool or urine (also look for "rose spots" on stomach) |
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Term
| How do you treat Salmonella infection? |
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Definition
1) Nontyphoid (controversial for gastroenteritis, but generally symptomatic if not antibiotic)
2) Septiciemia in either salmonella needs Antimicrobials (may not eliminate carrier state, so may need to remove ALL GALL STONES)
3) DONT USE intestinal motility inhibitors (lomotil)
** Live attenuated vaccine and Vi capsular vaccine available for travelers!** |
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Term
| How can travelers protect themselves from Salmonella poisoning? |
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Definition
1) Live attenuated vaccine and Vi capsular vaccine available for travelers!
2) Hygiene and Cooking Practices. |
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