Mechanisms of Microbial Infections Flashcards
Swine dysentery (B. hyodysenteriae)
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
Porcine enzootic pneumonia (Mycoplasma hyponeumoniae)
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
Which bacteria colonize ciliated mucosal epithelial cells for pathogenesis?
Porcine enzootic pneumonia (Mycoplasma hyponeumoniae)
Mannheimia (Pasteurella) haemolytica
Which disease uses M Cell Entry
Postweaning multisystemic wasting system (porcine circovirus type 2)
Describe the mechanism of entry for Porcine circovirus
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
What bacteria is considered a leukocyte trojan horse?
Rhodococcal pneumonia (R. equi)
MOA of Rhodococcal pneumonia (R. equi)
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.
List diseases that use dendritic cells to enter the immune system
Sheeppox and goatpox (poxviruses)
Describe the MOA for Sheeppox and goatpox (poxviruses)
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
Which pathogens use transcytosis entry?
Diamond skin disease of pigs (Erysipelothrix rhusiopathiae)
Describe the mechanism of entry that Diamond skin disease of pigs (Erysipelothrix rhusiopathiae) uses
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
Which bacterium gains entry via direct entry? (motility)
Leptospirosis
Describe the mechanism of entry of leptospirosis?
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
What organisms gains entry via nerve ending entry?
Bovine herpesvirus meningoencephalitis (bovine herpesvirus 5)
Describe exotoxins vs endotoxins
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
MOA of exotoxins and lipoteichoic acid
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
MOA of C. Botulinum, C. Tetani, Corynebacterium spp
A-B toxin system (B subunit binds to cell membrane and delivers a second molecule - A subunit into the cytoplasm
MOA of Helicobacter pylori, E. Coli, hemolysin, S. Pyogenes and Staphylococcus aureus
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
Lipoteichoic acid MOA
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
Endotoxins
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
MOA of LPS
Toxicity of LPS is attributed to Lipid A component of LPS
Immunogenicity of LPS is attributed to polysaccharide component of LPS
How does LPS evade the immune system?
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
List A-B toxins and mechanism
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
What are secretion systems?
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
Siderophores
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
What is the function of bacillibactin and petrobactin?
These are siderophres released by the bacteria B. Anthracis into the ECM and acquire iron for use by the bacterium
Describe a biofilm
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
What is Bap?
Biofilm-associated protein (Bap) has been implicated in the formation of a S. Aureus biofilm in chronic bovine mastitis
Describe bacterial capsules as a virulence factor
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
What are PAIs (pathogenicity islands)
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.
List the 4 mechanisms of antibiotic resistance
- Enzymatic deactivation
- Alteration of antibiotic binding sites
- Alteration of a metabolic pathway
- Reduced antibiotic accumulation in bacteria
List the MOA of bacterial resistance (enzymatic deactivation)
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
List the MOA of alteration of antibiotic binding sites for antibiotic resistance
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)
What is the MOA of alteration of a metabolic pathway with antibacterial resistance
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
Describe the MOA of reduce antibiotic accumulation for antibiotic resistance
Reduced antibiotic accumulation in bacteria through decreased membrane permeability to the antibiotic and/or ehnahced efflux via membrane pumps
What is the generation time (bacteria)
Is the time required for bacteria to divide or a colony of bacteria to double in number - can be as short as 15 minutes
How do bacteria transfer genes?
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
