Mechanisms of Microbial Infections

Question 1

Swine dysentery (B. hyodysenteriae)

Answer 1

A bacterial disease in which the mucus layer and thus goblet cells of the colon and cecum are the portal of entry and are the primary targets for microbial colonization and replication

Hemorrhagic diarrhea cause by bacterial hemolysins and proteases and inflammation

Mucus is a strong chemoattractant for spirochetes and is also important as a physical matrix and chemical substrate for colonization

Question 2

Porcine enzootic pneumonia (Mycoplasma hyponeumoniae)

Answer 2

Bacterial that targets cilia of ciliated mucosal epithelial cells in the respiratory system for microbial colonization and replication –> ciliostasis, lysis of the epithelial cells, reduced function of mucociliary apparatus and bronchopneumonia

**Mannheimia (Pasteurella) haemolytica also colonizes cilitated mucosal epithelial cells

Question 3

Which bacteria colonize ciliated mucosal epithelial cells for pathogenesis?

Answer 3

Porcine enzootic pneumonia (Mycoplasma hyponeumoniae)

Mannheimia (Pasteurella) haemolytica

Question 4

Which disease uses M Cell Entry

Answer 4

Postweaning multisystemic wasting system (porcine circovirus type 2)

Question 5

Describe the mechanism of entry for Porcine circovirus

Answer 5

Also called postweaning multisystemic wasting syndrome (porcine circovirus type 2)

Uses the alimentary system as its portal of entry –> crosses the mucosa using M cells that overlie Peyer’s patches (GALT)
….via M cells, the virus gaines access to an infects mucosa-associated lymphocytes and lymphs in GALT

Question 6

What bacteria is considered a leukocyte trojan horse?

Answer 6

Rhodococcal pneumonia (R. equi)

Question 7

MOA of Rhodococcal pneumonia (R. equi)

Answer 7

Bacterium crosses the mucosa and enters the respiratory system using a leukocyte (Trojan horse)
is phagocytized by mucosa-associated macrophages, carried via leukocyte trafficking to local lymphoid tissues (e.g. BALT) and then to tracheobronchial LN (regional) via afferent lymphatic vessels.

Question 8

List diseases that use dendritic cells to enter the immune system

Answer 8

Sheeppox and goatpox (poxviruses)

Question 9

Describe the MOA for Sheeppox and goatpox (poxviruses)

Answer 9

Viral diseases that use dendritic cells w/in mucosae of the respiratory and alimentary system as portals of entry and travel via leukocyte trafficking to lymphoid tissues

Question 10

Which pathogens use transcytosis entry?

Answer 10

Diamond skin disease of pigs (Erysipelothrix rhusiopathiae)

Question 11

Describe the mechanism of entry that Diamond skin disease of pigs (Erysipelothrix rhusiopathiae) uses

Answer 11

Transcytosis entry

Bacterium interacts w/ the cell membrane at the luminal surface of the cell, enters a vesicle formed by an invagination of the membrane, crosses teh interior of the cell in teh vesicle, fuses w/ the basolateral membranes of the cell and is then ejected from teh vesicle into the tissues

Question 12

Which bacterium gains entry via direct entry? (motility)

Answer 12

Leptospirosis

Question 13

Describe the mechanism of entry of leptospirosis?

Answer 13

Direct entry (motility) to cross mucosae

Is a highly motile spirochete and is able to move directly through mucosae or skin epithelial cells or between the cells via intracellular junctional complexes and reach well-vascularize ECM tissues

Question 14

What organisms gains entry via nerve ending entry?

Answer 14

Bovine herpesvirus meningoencephalitis (bovine herpesvirus 5)

Question 15

Describe exotoxins vs endotoxins

Answer 15

Exotoxins are secreted by living Gram-positive bacteria. (E.g. lipoteichoic acid from dead gram-positive bacteria)

Endotoxins are released from dead Gram-negative bacteria

Question 16

MOA of exotoxins and lipoteichoic acid

Answer 16

usually from gram-positive bacteria

Some act directly on cells and cause cytolysis

Others act via the A-B toxin system and bind to cell membranes w/ a receptor (B subunit) and deliver a second toxic molecule (A subunit) into the cytoplasm (e.g. C. Botulinum, C. Tetani, Corynebacterium)

Surface acting exotosins

Question 17

MOA of C. Botulinum, C. Tetani, Corynebacterium spp

Answer 17

A-B toxin system (B subunit binds to cell membrane and delivers a second molecule - A subunit into the cytoplasm

Question 18

MOA of Helicobacter pylori, E. Coli, hemolysin, S. Pyogenes and Staphylococcus aureus

Answer 18

Surface-acting exotoxins

Bind to cell membranes and form pores through which cell lysis occurs
S. Aureus also has pore-forming cytotoxins called alpha-toxin

Question 19

Lipoteichoic acid MOA

Answer 19

Binds to endothelial cells, interacts w/ circulating antibodies, activates the complement cascade, triggers release of ROS and N species, acid hydrolases, highly cationic proteinases, bactericidal cationic peptides, growth factors, and cytotoxic cytokines from neutrophils and macrophages

Question 20

Endotoxins

Answer 20

General term used to characterize any outer membrane-associated toxin of the cell wall
= gram-negative bacteria (e.g. E coli, Salmonella, Pseudomonas, Haemophilus, Bordetella)

most commonly refers to LPS complex

Question 21

MOA of LPS

Answer 21

Toxicity of LPS is attributed to Lipid A component of LPS

Immunogenicity of LPS is attributed to polysaccharide component of LPS

Question 22

How does LPS evade the immune system?

Answer 22

Outer membrane = protective barrier that

(1) impedes phagocytosis by macrophages
(2) facilitates colonization of target cells
(3) participates in the process of genomic variation - in which the outer membrane acquires naive polysaccharide components and evades host innate and acquired immune responses

Question 23

List A-B toxins and mechanism

Answer 23

Bacillus anthracis (anthrax)
C. Botulinum (botulism) 

Produce exotoxin (virulence factor) called A-B toxin

 1. B part acts as a ligand and facilitates cell-surface recognition of target cells and entry of the A part into the cell
 2. A enters via endocytosis

Question 24

What are secretion systems?

Answer 24

6 types have been described

Bacterial organelles that secrete or inject bacterial-derived toxins into the cytoplasm of target cells

• Type III best known (Salmonella, E. Coli)*
  
  • injects like a needle, specialized bacterial protein toxins like exotoxins into the cytoplasm of cells
  • these proteins then disrupt cell signal transduction and other cellular processes —> cell lysis

Question 25

Siderophores

Answer 25

Virulence factors that mediate the release of iron from intracellular iron stores

some bacterial require iron for colonization of mucosae and iron is plentiful in cells, but unavailable to bacterial b/c it is tightly bound to heme, ferritin, transferrin, or lactoferrin molecules

Ex. E. Coli and Salmonella spp —> this molecule scavenges bound iron from animal cells and makes it available for the bacteria

Ex B. Anthracis releases 2 siderophores (bacillibactin and petrobactin) into teh ECM, where they acquire iron for use by the bacterium

Question 26

What is the function of bacillibactin and petrobactin?

Answer 26

These are siderophres released by the bacteria B. Anthracis into the ECM and acquire iron for use by the bacterium

Question 27

Describe a biofilm

Answer 27

A virulence factor that forms an exopolysaccharide matrix called a biofilm on mucosal surfaces lining the oral and nasal cavities and the mammary duct system

Bap (biofilm-associated protein) has been implicated in the formation of a S. Aureus biofilm in chronic bovine mastitis

Question 28

What is Bap?

Answer 28

Biofilm-associated protein (Bap) has been implicated in the formation of a S. Aureus biofilm in chronic bovine mastitis

Question 29

Describe bacterial capsules as a virulence factor

Answer 29

Capsules are secreted by the bacterium and are tightly adhered to the bacterial cell wall

Aid in adhesion to mucosae and skin and are a reserve of nutrients, including water

Common in Gram-negative bacteria like E. Coli and Salmonella spp but can also occur in fungi like Cryptococcus neoformans

Question 30

What are PAIs (pathogenicity islands)

Answer 30

Clusters of genes that code for virulence facctors found in bacterial chromosomes

Virulence plasmids are clusters of self0replicating extrachromosomal genes for virulence factors located in plasmids w/in the cytoplasm of bacteria. Most bacteria have only 1 chromosome but may contain hundreds of copies of a specific virulence plasmid.

Question 31

List the 4 mechanisms of antibiotic resistance

Answer 31

1. Enzymatic deactivation
2. Alteration of antibiotic binding sites
3. Alteration of a metabolic pathway
4. Reduced antibiotic accumulation in bacteria

Question 32

List the MOA of bacterial resistance (enzymatic deactivation)

Answer 32

Occurs w/ beta-lactamases and extended-spectrum B0lactamases (resistant to cephalosporins and monobactams) produced by the bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa, E coli, Salmonella typhimurium

Question 33

List the MOA of alteration of antibiotic binding sites for antibiotic resistance

Answer 33

Penicillin-binding proteins (PBPs) such as occurs in infections with MRSA and other penicillin/methicillin oxacillin-resistant bacteria such as Strep pneumonia, vancomycin-resistant enterococci (VRE), and penicillin resistance S. Pneumonia (PRSP)

Question 34

What is the MOA of alteration of a metabolic pathway with antibacterial resistance

Answer 34

Sulfonamide-resistant bacteria that use preformed folic acid in place of para-aminobenzoic acid (PABA) a precursor for the synthesis of folic acid in bacteria inhibited by sulfonamides

Question 35

Describe the MOA of reduce antibiotic accumulation for antibiotic resistance

Answer 35

Reduced antibiotic accumulation in bacteria through decreased membrane permeability to the antibiotic and/or ehnahced efflux via membrane pumps

Question 36

What is the generation time (bacteria)

Answer 36

Is the time required for bacteria to divide or a colony of bacteria to double in number - can be as short as 15 minutes

Question 37

How do bacteria transfer genes?

Answer 37

Vertical gene transfer - pass to offspring (asexual reproduction) during DNA replication, this transfer results in offspring fully resistant to an antibiotic (ex antibiotic resistance transfer)

Horizontal gene transfer - direct bacteria-bacteria contact (conjugation) vis plasmids; chromosomal DNA (transofmration), bacteria-specific viruses (bacteriophages) that transfer DNA (transduction) between 2 closely related bacteria