LECTURE - Campylobacter and Helicobacter

Question 1

leading cause of GI infection in NA and number one in Canada

Answer 1

Campylobacter

Question 2

Characteristics of C. jejuni

Answer 2

• microaerophilic
• grows at 42C
• darting motility on wet mount vi polar flagella
• can develop coccoid, viable non-cultivatable (VNC) forms if eg. temp is reduced; resolved by passage through chickens
• see two polar flagella (TEM)
• most common human isolate
• causes colitis

Question 3

reservoir of Campylobacter infections

Answer 3

• intracellular capabilities (hides in cells) and is a way for it to be transmitted
• chickens are major reservoir (just like salmonella)
• invasive in humans but not in chickens

Question 4

result of Campylobacter infections

Answer 4

• GI disease
• ranges from asymptomatic carriage to life-threatening toxic megacolon
• typical disease: nausea, lower ab cramping and diarrhea (Watery or bloody) with fecal leukocytes and erythrocytes in patients
• recurrent or chronic infections can occur in immunocompromised patients
• very similar to salmonella

Question 5

Campylobacter presentation in developed vs developing countries

Answer 5

• developed: severe inflammatory diarrhea
• developing: mild, non-inflammatory diarrhea is more typical
• microbiome and hygiene hypothesis?

Question 6

Guillain-Barre syndrome

Answer 6

• sequelae of Campylobacter
• ascending bilateral flaccid paralysis, with various sensory signs, symmetric hand and arm weakness, w some involvement of the cranial nerves, sometimes leading to respiratory insufficiency
• serotype HS:19
• Abs to LPS to nerve gangliosides

Question 7

Reiter’s syndrome

Answer 7

• sequelae of Campylobacter

- a reactive arthritis, associated with HLA-B27

Question 8

Camylobacter antibiotic resistance

Answer 8

• most cases do not need antibiotics but immunocompromised could benefit
• Erythromycin and azithromycin are drugs of choice; Ciprofloxacin resistance is now common
• poultry = common source of infection therefore antibiotics use in chickens is bad (enrofloxacin)

Question 9

How C. jejuni causes disease

Answer 9

• far end (distal) of SI and into colon; invasive
• can also grow happily outside of cell but can also affect amoebae in freshwater
• four key determinants for invasion of host cells

Question 10

Four key determinants for invasion of host cells by C. jejuni

Answer 10

• motility and chemotaxis
• adhesion (no pili, nut other surface lipoproteins)
• LOS, LPS, capsule, N- and O- glycosylation of proteins; proteins that have sugars on them are common
• flagellar (type III-like) and type IV secretion systems

Question 11

genomic variability of C. jejuni

Answer 11

• small genome (1.7 Mbp)
• naturally competent; can acquire DNA through transformation from other strains of C. jejuni = juggles around genomes
• hyper-variable sequences allow slipped-strand mispairing and intragenomic recombination and variation; lack of known DNA repair genes may add to variation

Question 12

Features of H. pylori

Answer 12

• gram neg curved rod
• oxidase positive
• 4-7 polar, membrane-sheathed flagella
• microaeropilic
• few regulatory genes (only 4 two-component systems)
• chronic infection

Question 13

___ structures of C. jejuni can display molecular mimicry of neuronal gangliosides, which is linked to …

Answer 13

LOS; Guillain–Barré syndrome and Miller–Fisher syndrome

Question 14

The flagellin is modified by …

Answer 14

O‑linked glycosylation = required for flagellar assembly and is, therefore, important for motility, virulence and epithelial cell adherence and invasion

Question 15

N-linked glycosylation

Answer 15

N‑linked-glycosylation system modifies some periplasmic and outer membrane proteins. The N‑linked glycan is also important for colonization and epithelial cell adherence and invasion, but the role of this glycan in these processes is unclear.

Question 16

FAFLP

Answer 16

• used as a way to identify different strains of Campylobacter jejuni
• strains do not tend to segregate by their animal source. In other words, almost any FAFLP type isolated from human disease can be found in most any animal.

Question 17

genomic variability in C. jejuni

Answer 17

• small genome, about 1700 kbp (1.7 Mbp).
• naturally competent; can acquire DNA through transformation from other strains of C. jejuni.
• hyper-variable sequences allow slipped-strand mispairing and intragenomic recombination and variation. Lack of known DNA repair genes may add to variation

it’s hard to pin down reproducible phenotypic traits in Campylobacter like O and H antigens, because the genomes are constantly rearranging and changing the nature of the antigens that would be used to characterize strains

Question 18

The prevalence of Helicobacter pylori in developing and Western countries.

Answer 18

In developed countries, H. pylori is decreasing in prevalence so that most of the infections are in people over 50 years of age who likely acquired the infection during childhood. The infection in young persons is only seen in immigrants from high-risk countries.

Question 19

Diagnosis of H. pylori

Answer 19

• breath Test: 14C or 13C urea is ingested and production of 14CO2 or 13CO2 is measured
• fecal antigen test (this is simple and non-invasive, so has become the preferred test for Hp here)
• serum antibody test

Question 20

Triple Therapy for Eradication of H. pylori

Answer 20

• a proton pump inhibitor e.g., omeprazole, inhibits H+/K+ ATPase.
• clarithromycin (a macrolide antibiotic)
• metronidazole/Amoxicillin…for 7-14 days.

(Bismuth can also be used in combination with some of these drugs).

Question 21

Functions of Ureease, CagA, VacA, and LPS

Answer 21

H. pylori then injects the CagA protein into the host cells by a type IV secretion system and releases other toxic factors such as H. pylori neutrophil-activating protein (HP-NAP) and VacA. VacA induces alterations of tight junctions and the formation of large vacuoles. Vacuoles are evident in cells in culture and in the stomach epithelial cells of human and mouse biopsies, although they are not apparent in gerbils. The neutrophil activating protein HP-NAP crosses the epithelial lining and recruits neutrophils and monocytes, which extravasate and cause tissue damage by releasing reactive oxygen intermediates (ROIs). Injected CagA proteins cause alteration of the cytoskeleton, pedestal formation and signal the nucleus to release proinflammatory lymphokines, which amplify the inflammatory reaction with recruitment of lymphocytes and further induce the release of ROIs. The combined toxic activity of VacA and of ROIs leads to tissue damage that is enhanced by loosening of the protective mucus layer and acid permeation.