Sumby: Bacterial Pathogenesis Flashcards by Megan Foggia

Infections and parasitic diseases are the second leading cause of death behind cardiovascular disease

True

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Are most host:bacterial relationships parasitic?

no! mutualistic and commensal relationships predominate over parasitic - humans are colonized with bacteria that is essential and beneficial

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List some roles of the human microbiome (ecological community of things that share our body space)

nutrient acquisition
stimulates innate and adaptive immune responses
helps maintain epithelial boundary functions
provides colonization resistance of pathogens

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Problems with the human microbiome can lead to multiple conditions. Give a few examples.

psoriasis
obesity
inflammatory bowel disease
colorectal carcinoma

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Give an example of how the human microbiome promotes adaptation

In Japan, some people have a gene for digesting seaweed in their microbiome. In other areas, this gene is normally just in environmental bacteria, but it was somehow transferred to humans so they could digest seaweed.

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Clostridium difficle is a bacterial infection that is usually treated via oral antibiotics. Some spores are antibiotic resistant, however, and antibiotics also damage the gut microbiome. What is one alternative treatment option for these patients?

fecal microbiota transplantation
**donor stool is homogenized and placed in the GI tract during a colonoscopy to confer a better microbiome in the patient

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What does H. pylori infection do to the diversity of the stomach microbiome?

decreases the number and abundance of other bacterial species

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time between the moment the person is exposed to the microbe (or toxin) and the appearance of symptoms (note info is an important diagnostic clue)

incubation period

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time during which nonspecific symptoms occur.

prodrome period

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time during which specific clinical signs and symptoms occur.

disease period

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time during which symptoms resolve and health is restored.

recovery period

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What are the four stages of infection? What can happen in some people after the final stage of infection has resolved?

incubation
prodrome
disease
recovery

**after the recovery period, some people will become chronic carriers of the organism and may develop latent infections

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How does human to human transmission of microbes occur?

direct contact

indirectly through a vector (mosquito or other host)

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How does human-to-non-human transmission of microbes occur?

via animals (direct contact or animal vector)
soil
water
food

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Human diseases for which animals are the reservoir are called (blank)

zoonoses

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What are the main portals of entry into the body?

respiratory tract
GI
UG

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Give a clinical example of a disease that is passed from direct human-to-human contact

gonorrhea

**sexual transmission or when giving birth

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Give a clinical example of a disease that is passed from human-to-human via non-direct contact?

cholera

**fecal–>oral

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Give a clinical example of a disease that is passed from human-to-human via the placenta.

congenital syphillis

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Give a clinical example of a disease that is passed from the soil to humans

tetanus

**spores in soil enter skin

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Give a clinical example of a disease that is passed from a water source to humans

Legionnaire’s disease

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Give 3 different examples of diseases transmitted via an animal source.

directly - cat scratch fever (bacteria enter cat scratch)
insect vector - lyme disease
animal excretion - hemolytic-uremic syndrome caused by e. coli (bacteria in cow poo is ingested in undercooked hamburger)

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Give an example of a disease caused by bacterial transmission from one OBJECT to another

staph skin infection

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How can a bacterial pathogen be successful in living in a host?

enter the host and COLONIZE
avoid the immune system
acquire nutrients and REPRODUCE
exit the host and move to a new cell (disseminate)

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Is death of the host cell common in bacterial infections?

no; host and pathogen usually strike a balance that allows for both to survive

process whereby microbes attach to host cells or tissues.

adherence

asymptomatic harboring of microbes on or in the body; commensals as well as pathogens.

colonization

epithelial barrier breached; some host damage caused by a microbe; can be subclinical.

infection

Hospital-acquired infection, | occurs in 1/10 hospital patients.

Nosocomial infection

tissue destruction with specific signs and | symptoms.

disease

a microbe with the inherent capability of causing infection and disease in a host with an intact immune system.

pathogen

microbe that usually causes disease only in immunocompromised hosts

opportunistic pathogen

the ability of a microorganism to produce infection and disease in a host

pathogenicity

term that provides a quantitative measure of pathogenicity, or the likelihood of causing disease

virulence

gene products that enable a microbe to establish itself on or in a host (e.g. exotoxins)

virulence factors

Pathogens can show different virulence levels. Give an example of a pathogen with low virulence.

streptococcus salivarius

Give an example of a pathogen with moderate virulence.

escherichia coli **in colon, can cause urinary infections

Give an example of a pathogen with high virulence.

bordetella pertussis **causes whooping cough

Give an example of a pathogen with extremely high virulence.

yersinia pestis **cause of plague

this microbe causes a bloody diarrhea 16 hours to 2 days after ingestion of contaminated foods.

salmonella spp.

this microbe causes a bloody diarrhea 12 hours to 6 days after ingestion of contaminated foods.

shigella spp.

this microbe is a frequent skin colonizer, can contaminate food during preparation and secrete heat-stable enterotoxins. The toxins enter the blood and affect the vomiting control center of the brain, inducing vomiting 1 to 6 hours following ingestion.

staph. aureus

What are some things that make a bacteria virulent?

adhesins - can attach readily to host cells surface capsules or slime layers - prevent phagocytosis secretions - toxins exotoxins - cytotoxic proteins, degradative enzymes, superantigens endotoxins

(blank) facilitate adherence to human cells. They are fibers that extend from the surface of bacteria that mediate attachment to specific host cell or tissue components

fimbriae or pili

What are some adhesins that can promote pathogen adherence to host cells

Collagen-binding proteins Fibrinogen-binding proteins Fibronectin-binding proteins Laminin-binding proteins

(blank) or “slime layers” can promote pathogen adherence,

capsules **ex: strep. pyogenes binds epithelial cells via capsule - host cells have hyaluronic-acid-binding protein that binds the capsule

This is another name for the bacterial polysaccharide capsule or slime layer

glycocalyx

How does the polysaccharide capsule enhance immune evasion?

1. inhibits PAMPS on the microbe from binding recognized by pattern recognition receptors 2. inhibits C3b from binding to the microbe and also keeps phagocytic cells from binding to C3b on the microbe

What is a biofilm?

bacterial cells embedded in extracellular polymeric substance (a mixture of extracellular DNA, proteins, and polysaccharides) **part of the infectious cycle for many bacterial pathogens

How do biofilms assist pathogenic bacteria?

they help the bacteria to resist antibiotic treatments they trap nutrients for bacterial growth they allow bacteria to adhere to environmental surfaces and resist flushing they allow bacteria to live in close association w other bacteria they enhance immune evasion

What is a bacterial secretion system?

when a bacteria injects various effector molecules (toxins, enzymes) into the host cell cytoplasm and alters the cell's machinery or communication

What is the most common type of bacterial secretion system? Describe what this entails.

Type 3 secretion system; secretion apparatus is assembled in the bacterial cell wall that forms a needle to penetrate the host cell membrane - effector proteins in the bacterium can now be injected into the cytoplasm of the host cell (injectosome)

What is this: a protein that promotes bacterial invasion of tissues or cells

invasin

What are two types of invasins?

``` extracellular proteins (ex: hyaluronidase of Strep. pyogenes which splits the epithelial cells of tissues) intracellular proteins (ex: IpaB of Shigella flexneri) ```

Some bacteria bind to cell surface (blank) and induce their own endocytosis; some bacteria escape the (blank), and others multiply in the (blank). Bacteria may remain intracellular, or move through the cell and escape into the (blank) (transcytosis).

receptors; vacuole; phagolysosome; submucosa

These are microorganisms that synthesize proteins that are toxic to their hosts; they are excreted into the environment or are found associated with the microbial surface; usually have some degree of host cell specificity

exotoxins

Exotoxins are antigenic and induce antibodies called (blank). Exotoxins can be modified to form (blank), which are antigenic but not toxic (e.g., tetanus toxoid vaccine).

antitoxins; toxoids

What are the 4 classifications of exotoxins?

Type 1: cell surface active (superantigens like toxic shock syndrome toxin) Type 2: membrane damaging (Clostridial alpha-toxin with phospholipase activity) Type 3: intracellular (cholera toxin) Type 4: extracellular damaging (hyaluronidase, collagenase)

Describe the mode of action of the cholera toxin.

The cholera toxin has an A1 and an A2 domain. The A1 domain is cleaved from A2, making A1 catalytically active. ADP ribosylates Gs, which results in continuous activation of adenylate cyclase which leads to high cAMP levels. Increased cAMP activates the CFTRs causing a dramatic efflux of ions and water leading to diarrhea.

bind simultaneously to T cell receptors and MHC class II molecules outside of the normal peptide-binding groove. Hyper-stimulate T cells to secrete cytokines (cytokine storm). Up to 20% of all peripheral T cells can be stimulated.

superantigens ex: S. aureus: Toxic shock syndrome toxin Staph. enterotoxins S. pyogenes: Strep. pyrogenic exotoxins

lipopolysaccharides (LPS) located in the outer membrane of Gram-negative bacteria; they are not secreted by bacteria; poorly antigenic

endotoxins

What is the toxic component of LPS? What does this do?

Lipid A; induces the overproduction of cytokines and inflammatory mediators from macrophages leading to septic shock (fever, hypotension, multi-organ system failure)

What two cascades does LPS activate?

coagulation **disseminated intravascular coagulatioon | complement **increased vascular permeability

What makes E. Coli uropathogenic?

fimbriae **fimbriae are significant virulence determinants of uropathogenic E. coli, the most common cause of urinary tract infections. These fimbriae mediate attachment of uropathogenic strains to uroepithelial cells

What makes the capsule of Klebsiella pneumoniae virulent?

it resists phagocytosis

What kind of environmental factors may control expression of virulence genes?

temp pH osmolarity

In Corynebacterium diphtheria, the gene for diphtheria toxin is regulated by (blank)

iron concentration

In Borrelia burgdorferi, expression of surface proteins is regulated by (blank)

temperature

the production and release by individual bacteria of molecules called autoinducers that modulate gene expression in response to the density of a bacterial population.

Quorum sensing

What does bacterial quorum sensing do?

facilitates coordinated responses by bacterial populations Ex: if there are a lot of bacteria in a colony, this may lead to a coordinated response like biofilm formation

Some virulence factors are present in all isolates of a given pathogenic species, part of the “core” (blank). Some virulence factors are variably present between isolates, usually encoded on (blank) (e.g. plasmids, bacteriophages, pathogenicity islands [PAIs]). Different isolates of the same bacterial species can have widely different (blank) characteristics.

chromosome; mobile genetic elements; virulence

How do most bacterial plasmids replicate? What genes might plasmids carry? Do all pathogen isolates have plasmids?

extra-chromosomally; may contain genes for virulence factors or Ab resistance; no, some have many some have non

Plasmids have essential roles in the ability of this bacteria to cause disease

Bacillus anthracis

What are the two stages of bacteriophage replication? Which form of phage is likely to encode virulence factors?

lytic or lysogenic; lysogenic

collections of genes, many of which encode virulence factors, that are clustered together on the bacterial chromosome

pathogenicity islands

How are pathogenicity islands usually acquired?

via horizontal gene transfer or conjugation

What determines the E.Coli pathotype?

mobile genetic elements

What can antibiotic treatment of E.Coli infection lead to?

hemolytic uremic syndrome **the result of rapid/premature death of RBCs, the remnants of which clog the kidneys and lead to renal failure

There is also evidence that Ab increase (blank) by E.Coli

Shiga-like toxin

List a few ways in which bacteria defend against host immunologic clearance

``` encapsulation antigenic mimicry antigenic variation anti-Ig proteases destruction of phagocytes inhibition of chemotaxis/phagocytosis/phago-lysosomal fusion ```

This organism expresses an arsenal of virulence factors to thwart the host immune response

GAS

What are two ways in which bacteria can avoid opsonization via antigenic variation?

1. phase variation: expression of surface proteins switched on or off 2. antigenic variation: surface antigens switched from one type to another

List a few intracellular bacterial pathogens that avoid humoral immunity

``` Mycobacterium spp. Brucella spp. Francisella spp. Rickettsia spp. Legionella pneumophila ```

How do some microorgansisms inhibit killing following phagocytosis?

1. inhibition of phago-lysosomal fusion 2. resistance to lysosomal enzymes 3. escape from phagolysosome to cytoplasm