Term
| How do pathogens compensate for the inherent instability of many mobile genetic elements and the need to maintain different mobile element simultaneously? |
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Definition
1) Integrate into the chromosome for stability
- Phage (lysogeny in Cholera and Diphtheria)
- Transposons (integration)
2) Mobile elements acquire many complementary virulence genes
- Pathogenicity islands |
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Term
| What is the role of lysogeny in Diphtheria? |
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Definition
Gene encoding diptheria toxin is carried on beta-phage, which infects Corynebecterium, and is stably maintained (without producing progeny).
- Virulence gene is integrated into host bacteria and expressed under low-iron conditions to inhibit protein synthesis by ADP-ribosylating eIF2 |
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Term
| How does Iron regulate expression of C. diphtheriae toxin? |
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Definition
Remember, beta-phage mediated integration of toxin gene.
1) Under low-iron conditions, toxin is transcribed and 2DTXR:Fe2+ dimers dissociate
2) Under high-iron conditions, no toxin is produced. |
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Term
A patient presents with thick gray adherent pseudomembranes over the tonsils and throat.
A pathogen is isolated using selective media with tellurite salts. Samples indicate, gram-positive, club-shaped rods in "chinese letter" formations.
What is the pathogenesis of this pathogen? |
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Definition
Corynebacterium diphtheriae
**NOT INVASIVE, but can be absorbed in mucosal epithelium**
1) Colonization of nasopharynx (inhaled) or cutaneous surface (settle on skin at site of wound) through aerosole droplets
2) 1-7 days after toxin production begins, localized necrosis develops (malaise, soar throat and enlarged cervical lymph nodes)
3) Necrosis leads to pseudomembrane formation, which can ultimately block respiration and cause death |
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Term
| How do you diagnose/treat Dipththeria? |
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Definition
1) Diagnosis made on clinical grounds (pseudomembrane and cervical lymph nodes) and conformed in the lab with culture and toxin testing
2) Antitoxin and antimicrobials (prevent with DPT) |
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Term
How can pathogenicity islands be transferred between bacteria?
What bacteria is an example of this? |
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Definition
Lysogenic infection with V. cholera (toxin increases cAMP through ADP-ribosylation of Gs)
V. cholerae phage binds toxin-coregulated pilus (TCP) and carries cholera toxin, accessory enterotoxins and adhesins |
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Term
A patient returning from Peru exhibits voluminous, watery diarrhea (painless). He is lightheaded and severely dehydrated.
No white blood cells are found in stool, but gram-negative comma-shaped rods are present.
What is the reservoir/transmission of this pathogen? |
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Definition
V. cholerae (motile, oxidase-positive, facultatively anaerobic)
- O1 serotype is most important, with O139 also being important
1) Estuary waters and colonized, asymptomatic people
2) Pandemics with contaminated food/water through fecal-oral route. |
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Term
| What virulence factors are associated with Vibrio cholerae? |
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Definition
1) Cholera toxin ADP-ribosylates Gs subunit leading to increases in adenylate cyclase and cAMP in intestine (massive fluid/electrolyte loss).
2) Accessory enterotoxins
- ZOT for tight junctions
- ACE for ion channels)
3) Colonization factors
-Toxin-coregulated pilus (TCP) for attachment to epithelium
- Fimbrial and afimbrial adhesions (O139 polysacharide capsule), LPS
- Flagella
4) Virulence factor expression regulators
- TcpP, ToxR and ToxS membrane proteins act together to activate ToxT transcription
- ToxT binds promotors of virulence genes |
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Term
| How is virulence factor gene expression regulated in V. cholerae? |
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Definition
1) TcpP, ToxR and ToxS membrane proteins act together to activate ToxT transcription
2) ToxT binds promotors of virulence genes such as PctxAB and Ptcp to make Toxin and TCP, respectively |
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Term
| What is special about the O139 strain of V. cholerae? |
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Definition
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Term
| What is the pathogenesis of the pathogen that causes "rice-water" diarrhea without fecal leucocytes? |
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Definition
**NOT INVASIVE (like Diphtheria)
1) After ingestion, V. cholerae move through intestinal mucus with flagella and attach to enterocytes with TCP
2) Produce CT, which binds to enterocyte and increases cAMP, which binds kinases that activate ion channels (CFTR)
3) Massive fluid/electrolyte loss (moderate to severe diarrhea) occurs hours/days later.
4) Fluid loss causes sunken eyes, poor skin turgor, cardiac issues and shock.
**In Cholera gravis, diarrheal fluid loss is 1L/h, with "rice-water" excrement** |
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Term
| How do you diagnose/treat Cholera? |
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Definition
1) CLINICAL followed by lab confirmation
2) Rapidly restore fluid/electrolytes, perhaps with IV fluids and use Azithromicin to lessen severity/duration. |
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Term
True or False:
Cholera toxin is "halotolerant" |
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Definition
| True- resists elevated NaCl (survives gastric acid). |
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