INFECTIONS OF THE GI TRACT

Question 1

1What are the major presentations of gastro-intestinal infections? Please, describe the clinical symptoms for one of them and give 2 examples for associated pathogens.

Answer 1

Usually GIT infections are present with gastrointerstinal symptoms like diarrhoea and abdominal pain. They may spread to other parts of the body (extraintestinal infections)

Diarrhoea is the passing loose fluid stools more than 3times a day or more than the individuals regular frequency of passing stool.
pathogens- Vibrio cholera, Rotavirus and Escherichia coli.

Question 2

What is a zoonotic disease?

Answer 2

A zoonotic disease is an infection or disease that is transmissible from animals to humans under natural conditions. This can be from domestic animals, wild animals, pets or even food. Rabies, Anthrax and bird flu.

Question 3

Name 3 intestinal signals, what they are an indicator for and a pathogen that senses them.

Answer 3

Metabolic signals
S. enterica Bile acids, SCFA, fucose - Proximity to epithelial surface
- Location to preferred regions along the GI tract
Physico-chemical signals
Salmonella pH, osmolarity, oxygen tension - Transition from lumen to tissue (salmonella)
- Proximity to epithelial surface (Salmonella)
Mechanical signals
E. coli Attachment, viscosity - Target cell contact (E. coli)
- Transition from lumen to mucus layer (Vibrio)
Example: V. cholerae and bile sensing.

Question 4

What is a type-3-secretion system? Please, describe the mechanism of action and name 2 pathogenic species, that employ them during infection.

Answer 4

Multi-protein complex, spanning inner/outer bacterial membrane, anchored to the host membrane through the translocon, direct delivery of effector proteins into host cytosol to induce uptake and modulate host physiology (e.g. Salmonella, pathogenic E. coli, Yersinia, Xanthomonas,Pseudomonas). The translocon (also known as a translocator or translocation channel) is a complex of proteins associated with the translocation of polypeptides across membranes.

Question 5

What is the full taxonomic name of Salmonella Typhimurium?

Answer 5

Salmonella enterica ssp. enterica (I) serovar Typhimurium

Question 6

Name 2 Salmonella-Serotypes, that cause extra-intestinal infections and that are restricted to humans.

Answer 6

S. Typhi
S. Paratyphi A
S. Paratyphi C

Question 7

Explain one mechanism how extra-intestinal Salmonella serotypes evade immune recognition. Name the corresponding serotype.

Answer 7

Typhoid fever caused by Salmonella enterica serovar (S.) Typhi differs in its clinical presentation from gastroenteritis caused by S. Typhimurium and other non-typhoidal Salmonella serovars. The different clinical presentations are attributed in part to the virulence-associated capsular polysaccharide (Vi antigen) of S. Typhi, which prevents phagocytes from triggering a respiratory burst by preventing antibody-mediated complement activation. Paradoxically, the Vi antigen is absent from S. Paratyphi A, which causes a disease that is indistinguishable from typhoid fever. Here, we show that evasion of the phagocyte respiratory burst by S. Paratyphi A required very long O antigen chains containing the O2 antigen to inhibit antibody binding. We conclude that the ability to avoid the phagocyte respiratory burst is a property distinguishing typhoidal from non-typhoidal Salmonella serovars that was acquired by S. Typhi and S. Paratyphi A independently through convergent evolution.
Reminder of convergent evolution; the independent development of similar traits or features (as of body structure or behavior) in unrelated or distantly related species or lineages that typically occupy similar environments or ecological niches

Question 8

Please describe the composition and mechanism of action of the cholera toxin of Vibrio cholerae.

Answer 8

CT is made up of two types of subunits. The larger A subunit is located centrally, while the five B subunits are located peripherally. The A subunit consists of two domains (A1 and A2). In both the toxins, the upper A1 domain of the wedge-shaped A subunit is held above the plane of the doughnut-shaped pentameric B subunits by the tethering A2 domain, which in case of CT, is an alpha helix for almost its entire length. The carboxy-terminal of the A2 passes through the opening created by the doughnut arrangement of the B subunits. The four carboxy-terminal residues of the A2 chain are Lys-Asp-Glu-Leu (K-D-E-L).
Cholera toxin, by acting as a classical A-B type toxin, leads to ADP-ribosylation of G protein, and constitutive activation of AC, thereby giving rise to increased levels of cyclic AMP within the host cell. As a result, electrolyte imbalance occurs due to a rapid efflux of chloride ions by the cystic fibrosis trans-membrane conductance regulator (CFTR), decreased influx of sodium ions, leading to massive water efflux through the intestinal cells, thereby causing severe diarrhoea and vomiting, the cardinal clinical signs of cholera. Diarrhoea, if untreated, leads to severe dehydration, electrolyte abnormalities and metabolic acidosis, almost inevitably resulting in death.

Question 9

Why can O-antigens not be used for serotyping of C. difficile isolates?

Question 10

What are the characteristic differences between cytotoxic and cytotonic toxins. Which diarrheal manifestation are they associated with?

Answer 10

Cytotonic refers to no structural damage of the cell. For example, toxins which causes secretory diarrhea are cytotonic toxins (Vibrio cholerae). Related to the Inflammatory dierrhea type.
On the other side, cytotoxic toxins cause profound changes to cell morphology and lead eventually to cell death. In some cases, fulminant colitis and pseudomembraneous colitis can develop (Clostridoides difficile). Related to the secretory diarrhea.