1. Case Study 4 Salmonella

Front 1

How do many pathogens cause disease?

Back 1

They enter into (invade) host cells and some of these pathogens live within phagocytic cells (macrophages) whereas others live in non-phagocytic cells such as mucosal epithelial cells

Front 2

What two groups can intracellular pathogens be divided into?

Back 2

1) facultative intracellular pathogens
2) Obligate intracellular pathogens

Front 3

Faculatative intracellular pathogens

Back 3

-Can live within or outside host cells

Front 4

Obligate intracellular pathogens

Back 4

Must grow within host cells and cannot be cultivated outsider their host

Front 5

Why are intracellular environments desired by some bacterium?

Back 5

-Intracellular environment is a rich source of nutrients and energy (amino acids, ATP and other nucleoside triphosphates)
-Intracellular environment also shields them from the host's immune system (complement, antibodies, neutrophil phagocytosis) and provides protection from many antibiotics that don't penetrate host cells

Front 6

How do we deal against intracellular pathogens?

Back 6

-Cell mediated immunity
-T cell effector mechanisms and activation of macrophages

Front 7

What is salmonella an example of?

Back 7

An intracellular pathogen that hides from the host's immune defences

Front 8

Describe the structure of salmonella

Back 8

-Consist of a range of very closely related bacteria (many that cause disease in humans and animals)
-Gram-negative, flagellated, facultatively anaerobic bacilli

Front 9

What kind of antigens does salmonella possess?

Back 9

3 major ones
1) H or flagellar antigen
2) O or somatic antigen
3) K or capsular antigen

(Note, one major antigen of the capsular antigen, Vi is possessed by only a few serovars of Salmonella, primarily those that cause typhoid fever)

Front 10

How is Salmonella spread?

Back 10

It is transmitted from the feces of infected people or animals to other people or other animals via contaiminated food or drink
-Contaiminated foods are frequently of animal origin (beef, poultry, milk, eggs) but all foods including vegetables may become contaminated

Front 11

What are the two main diseases associated with Salmonella infections?

Back 11

Salmonellosis
Thyphoid fever

Front 12

What accounts for the diversity of Salmonella?

Back 12

The ability of the bacterium to undergo antigenic variation , to create variation in their genes for their H, O and K antigens through recombination, alterations in length, gene duplication and point mutations

Front 13

What are serovars?

Back 13

It is a strain differentiated by serological means

Front 14

What are serological methods?

Back 14

They employ antibodies and include aggultination tests, ELISAs and Western blots
-It is antibody binding that all serological tests ultimately detect

Front 15

What is teh premise behind serological tests?

Back 15

The basic premise is that antibodies are highly selective in terms of proteins (or other cell structures) to which they bind, to the point that they are able to distinguish the proteins expressed from one strain amongst many strains
-Recall that a strain is a subset of bacterial species differing from other bacteria of the same species by some minor but identifiable difference

Front 16

What is a sterotype?

Back 16

It is an antigenic property of a cell or virus identified by serological methods
-As a verb, serotype means to classify according to serovor or to assign to a particular serovar

Front 17

What are biovars

Back 17

They are strains that are differentiated by biochemical or other non-serological means

Front 18

What kind of virulence factors does salmonella possess?

Back 18

1) Adhesions
2) LPS
3) Capsules
4) Two type III secretion systems
5) Ability to replicate inside host cells

Front 19

Where are the genes that encode the virulence factors located in Salmonella?

Back 19

In the pathogencitiy islands found in the genome
-Pathogenicity islands are large regions of DNA (10-200 kb) that encode clusters of genes associated with virulence (toxin genes, adhesion genes, invasion genes)
-The genes may have been acquired during evolution by horizontal gene transfer and are often associated with bacteriophage or prohage genes
-These pathogenicity islands are not found in the genomes of nonpathogenic members of the same or related species

Front 20

What is SPI1

Back 20

Salmonella pathogenicitiy island 1
-Contains many genes associated with virulence as well as genes involved in regulation of these virulence genes
-Contains a group of genes called inv genes that are responsible for the membrane ruffling associated with the invasion of host cells by Calmonella
-Inv genes along iwth other genes encode a type III secretion system that is used to inject proteins (also encoded by SPI1) into cytolpalasm of eukaryotic cells to mediate invasion and inflammation

Front 21

What is the disease of salmonella?

Back 21

Salmonella enterica are involved in causing diseases of the intestines
-Three main serovars of salmonella enterica are Typhi, Typhimurium and Enteritidis

Front 22

What is a weakness of salmonella?

Back 22

It is very acid sensitive
-So individuals who produce little or no stomach acidity are at increased risk for Salmonella infections
-Large inoculum is required to infect humans with normal stomach acid but inoculum size can be reduced 100 fold when introduced with bicarbonate

Front 23

If the salmonella manage to escape being killed by the stomach acid, where do they go next?

Back 23

They pass into the small bowel where invasion into the host cell may occur

Front 24

What causes tyhpoid fever?

Back 24

S. thyphi
-It is only pathogenic to humans, no other animal host has been identified
-Major source of infection is from drinking contaminated water or consumption of food that is washed or irrigated with contamined water

Front 25

Whats a food infection

Back 25

Symptoms arise only after the pathogen has had time to replicate in the intestine
-Thus, syomptoms can develop several days after ingestion of contaiminated food or water

Front 26

What is food poisoning?

Back 26

Also called food intoxication
-Results from the ingestion of food that is contaiminted with preformed and biologically active toxins
-Bacteria produced that produced the toxins do not have to replicate in the host or even be alive in the contaminted food

Front 27

S. typhimurium does not produce any of the enterotoxins that seem to be necessary for pathogenic bacteria to cause diarrhea. How do Salmonella cause the diarrhea and pain associated with salmonellosis

Back 27

1) Bacteria inject proteins into the intestinal cell via a type III secretion system
-These injected proteins discrupt normal host cell function and promote internalization of bacteria
-INfected host cell responds by producing chemokines and other inflammatory mediators which attract neutrophils to infected area
-Neutrophils produce prostaglandin which acts on intestinal epithelial cell to increase the internal concentattion of cAMP
-INcreased levels of cAMP cause an inhibitition of the upertake of Na+ ions and increased secretion of CL- ions
-As concentration of NaCL increases in the lumen of the intestine, water is lost from the tissues into the lumen resulting in diarrhea
-Abdominal pain is due to a inflammatory response that results with the recognition of the bacterium's LPS and subsequent release of cytokines as well as that caused by SPI1 effects

Front 28

How do we diagnose salmonella infections?

Back 28

Isolation of orgnaisms from clinical specimens such as blood or stool
-Specimen is plated onto selective and differential media and identification of suspicious colonies is done by biochemical tests
-Serotype is identified by antigenic analysis of O (cell wall antigen) and H (flagella antigen) antigens using polyvalent and specific antisera