Intro to Pathogens 9/9

Question 1

Microbiota

Answer 1

Normal flora (bacteria, fungi, protozoa) that live on or within the bodies of animals and plants

• do not cause disease in healthy individuals
• have an adapted/noninvasice role by limitations of environment (commensalists or mutualists)
• extremely abundant in humans ~ 10^14

Can do good!

• Prevent or suppress pathogens
• Synthesize vitamins (Vitamin K), absorption of nutrients
• Abs produced to commensals cross-react with pathogens having related or shared Ag
• Bacteriocins
• Endotoxin release enhances immune response

Question 2

Commensalism

Answer 2

Many of the normal flora neither hurt, harm, nor benefit the carrying host.

Question 3

Mutualism

Answer 3

• Mutualisms are symbiotic interactions between two organisms in which both organisms benefit.
• One of the most important mutualistic roles of normal flora is as microbial antagonists.
• To prevent colonization by pathogens through bacterial interference

Question 4

How does normal flora become pathogenic?

Answer 4

Can become pathogenic in in tissue(s) outside their normal niche

• Penicillinase + bacteria can interfere with therapy
• Confusion in Dxs due to resemblance to some pathogens
• Streptococcus viridans seeds bloodstream following dental procedure, settles on heart valve, infectious endocarditis

Question 5

Resident and Transient Flora

Answer 5

• Resident: constant & well defined

–>Role of resident flora: Interference

• Competition for receptors or binding site on host cells
• Competition for nutrients
• Mutual inhibition by metabolic or toxic products
• Mutual inhibition by bacteriocins or antibiotics
• Transient: exposure to environment, does not cause disease or establish permanently
• Colonization: establishment of a microbial population
  Acquisition of an new organism

Question 6

Acquisition of normal flora

Answer 6

Environmental acquisition:

• In utero mammals are as sterile as any internal organ.
• Through contact with adults, older children, and the rest of their environment newborns acquire all their normal flora.

Large intestine: supports huge anaerobic populations, kept anoxic (O2 depleted) by facultative anaerobes.

• Birth canal, breast feeding, bottle feeding
• As the child grows facultative flora is acquired from oral exposure to feces.
• Strict anaerobes can colonize only after sufficient facultative organisms are established enough that oxygen concentrations are maintained at drastically reduced levels.

Question 7

characteristics of a “pathogen”

Answer 7

Two mechanisms: invasion of tissue -or- production of toxins

• Invasiveness: ability to invade host tissues
• Capsules: some bacteria produce hyrdophilic gels that inhibit phagocytosis
• Adaptation: microenviconments of the host body provide habitats for bacteria that are capable of selective tissue invasion
• Extracellular enzymes: some bacteria produce enzymes like hyaluronidase or collagenase that degrade host tissues

Question 8

Virulence:

Answer 8

the combination of invasiveness and toxigenicity

• LD = lethal dose
• LD50 = at what point 50% of the population dies - a measurement of virulence (%dead vs. dose)
• variability in virulence potential may be genotypic or phenotypic

Question 9

Potential Pathogens

Answer 9

General factors –
Age, immunization history, prior illnesses or coexisting illness, trauma, nutrition, pregnancy, emotional state

Medical care:

1. breaching of the skin (with intravenous devices or surgical incisions) or mucosal surfaces (with endotracheal tubes or bladder catheters)
2. introduction of foreign bodies
3. alteration of the natural flora with antibiotics, and treatment with immunosuppressive drugs.

Question 10

Communicability

Answer 10

= transmission of disease

Communicability: infectious disease can be transmitted either directly (e.g. person to person) or indirectly (e.g. contaminated water).

Factors involved in the communicability of an infectious agent include:

• Source, including dormant or latent infections (carriers).
• Number of infectious agents released from a host.
• Capability of surviving transit from host to host.
• Percentage of the host population that is susceptible to the agent.
• ID50 (% infected vs. dose)

Question 11

Toxigenicity (exotoxins and endotoxins)

Answer 11

• Toxigenicity: the production of toxins.
• Exotoxins: secreted proteins that are generally very toxic but heat labile. Exotoxins are found mostly in Gram-positive organisms.
• Endotoxins: complex polysaccharides (LPS) that are a part of the bacterial cell wall. These toxins are released when cells lyse, are generally heat stable, and found mostly in Gram-negative bacteria.

Question 12

Stages of pathogenic Process

Answer 12

1. Adhere
2. Must evade local immune system
3. Must replicate
4. Must evade systemic immune system (need to downregulate adaptive response)
5. Must escape body for transmission to new host

Generally:

• Intracellular pathogens generally produce chronic disease
• Extracellular pathogens generally produce acute disease

Question 13

Stages of Infections

Answer 13

1. Incubation period: replication phase – evading immune response
2. Prodrome period: Non-specific symptoms
3. Specific-illness period; Characteristic signs and symptoms
4. Recovery period
5. Latent infections

Question 14

Viruses: characteristics and replication

Answer 14

• obligate intracellular parasites
• contain DNA or RNA, ss or ds
• surrounded by protein coat (“capsid”)
• certain viruses contain an additional phospholipid bilayer (“envelope”) surrounding capside that is derived from host cell
• Viral replication:

1. virus recognizes and attaches to host (specific)
2. viruses adsorb to host cell surface via receptor molecules (often temp. indepen)
3. Penetration into host cell may occur in three ways (1. translocation of the PM, 2. pinocytosis into cytoplasmic vacuoles, 3. fusion of the PM with the viral envelope)
4. non-enveloped viruses may enter via translocation or pinocytosis; enveloped viruses enter via fusion
5. once inside, virus uncoats and rleases the viral genome for replication
6. viral nucleic acid replication results in new viral protein that are packaged and released

Question 15

Viruses: effects on host cells

Answer 15

Viruses can have one of several different effects on their cellular hosts.

Abortive infections

• result when a virus mistakenly infects a cell that does not permit viral replication

Cytolytic infections:

• lead to cell lysis and release of large numbers of virions

Persistent infections

• may be productive, latent or transforming

Question 16

Rhinovirus

Answer 16

• Rhinoviruses are the most common viral infective agents of the common cold.

Two modes of transmission:

• aerosols of respiratory droplets
• contaminated surfaces

Human rhinoviruses are composed of a single-stranded positive sense RNA & capsid. It is not enveloped.

The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.

Question 17

Bacteria: two types

Answer 17

• Unicellular prokaryote microorganisms
• found everywhere, very few are pathogens

Gram-negative bacteria have a thin layer of peptidoglycan located between the cytoplasmic membrane and a second outer membrane. This region is known as the periplasmic space.

• Lipopolysaccharides: (yellow)
  found only in Gram-negative bacteria.
  composed of lipid A, which binds the LPS in the outer membrane

Gram-positive bacteria have a thick layer of peptidoglycan external to the cytoplasmic membrane.

• Peptidoglycan:
  a polymer of alternating N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG)
• Lipoteichoic acids: (green line)
  found only in Gram-positive bacteria
  extend though the entire peptidoglycan layer and appear on the cell surface.
• *

Question 18

Bacterial structures:

Answer 18

Shapes:

• Spheres: cocci
• Rods: **bacilli **
• Slightly elongated cocci: coccobacilli
• Corkscrew-like appearance: spirochetes
• May also be arranged in pairs, clusters or chains

Surface Appendages:

Flagella: provide motility

• Flagella are composed of flagellins (proteins) that make up the long filament. This filament is connected to a hook and rings that anchor the flagella in the cell wall.
• single polar flagellum (monotrichous)
• several polar flagella (lophotrichous)
• several flagella at each end of the cell (amphitrichous)
• many flagella covering the entire cell surface (peritrichious)

Pili: These surface appendages come in two distinct forms having distinct purposes (fimbrae)

• Sex pili: involved in conjugation, the transfer of genetic information from one cell to another
• Common pili: can be found covering the cell surface. These structures provide the means for attachment to host cells and often play an important role in colonization

Capsules:

• Composed of high molecular weight polysaccharides.
• Capsule: mechanism of evasion via strongly adhering to the cell wall
• Slime layer: loosely associated

Question 19

Bacterial transmission

Answer 19

• Many bacteria rely on human-to-human contact
• Others survive in the environment short periods of time

Endospores:

• resistant to heat, radiation and drying
• dormancy for hundreds of years
• favorable conditions for growth spores germinate and return to the vegetative state.

Question 20

Aerobic vs. Anaerobic Bacteria

Answer 20

Aerobic bacteria

• requires oxygen as a terminal electron acceptor
• will not grow under anaerobic conditions

Anaerobic bacteria

• Energy is from fermentation reactions
• Oxygen can be poisonous

Facultative anaerobes

• grow under aerobic conditions and can also ferment

Question 21

Colostridium difficile (C. diff)

Answer 21

DISTINCTIVE PROPERTIES:

• Gram-positive, rod-shaped, spore-formers
• obligate anaerobes
• ubiquitous saprophytes
• part of normal flora

C. difficile produces large sub-terminal spores and two different toxins:

• Toxin A (enterotoxin causing fluid accumulation in the intestine)
• Toxin B (a cytopathic agent)
• Patients secrete large numbers of spores in feces = reservoir

Can’t compete with normal intestinal flora

Antibiotic-associated colitis:
Diarrhea, cramps, pseudomembranous colitis (PC)

Question 22

Fugi: Basic Properties

Answer 22

Grow as either yeasts or mold…

Yeast:

• single cell (oval or round)
• Form bacterial-like colony

Mold:

• (long filament (hyphae)
• Form a mat (mycelium)

Thermally dimorphic fungi:

• Change often occurs when free living form becomes parasitic
• At ambient temperature – mold
• In host tissues – yeast
• Candida is exception and forms reversed (in host tissue it’s a mold)
• Most fungi are aerobes
• Some facultative anaerobes; no strict anaerobes
• Require preformed carbon sources

Structure:

• Cell walls: contain Chitin
• cell membranes: contain ergosterol and zymosterol

Question 23

Medical Mycoses

Answer 23

Mycoses = fungal infection

Superficial Mycoses

• dead layers of skin, hair – mostly
• Cosmetic- don’t do major harm
• limited to outer layers of skin/hair b/c it likes off products of keratin as C source

Cutaneous Mycoses

• epidermis, hair, nails

Sub-cutaneous

• nails, deeper skin layers
• due to chronic infections or ganulomatous lesions - fungi enters through broken skin
• ex. Meduro foot disease: caused by free-living saprophytic fungi entering through broken skin.

Systemic or deep mycoses

• Internal organs
• Opportunistic infections in immunocompromised host
• No human-to-human transmission
• Restricted to geographical niche
• Most infections are sub-clinical

Commonalities of Fungal infections:

• patient can remember trauma (bite, splinter, thorn)
• location of problem relates to wounds
• etiological agents: from soil or decaying vegitation
• treatment: excision/amputation

Question 24

Candida Albicans

Answer 24

• (most abundant fungus on body, part of natural flora, and is abundant in GI tract)
• Grows as both yeast and filamentous cells- likes to grow in warm moist places
• Opportunistic: in immunocompromised individs
• Grows in biofilms on implantable devices
• Superficial: thrush (oropharynx), vaginitis (yeast infections)
• Systemic: Candidemia (fungemia) - can occur in normal healthy person if normal flora has gotten into a place where it shouldn’t be

Question 25

Parasitic Taxomonic Groups

Answer 25

Protozoans * Single-celled organisms with a true, membrane bound nucleus Metazoans --\>Helminthes (worms) * Nematodes * Platyhelminthes (Cestodes, Trematodes) Arthropods * Insects (lice)

Question 26

parasitic definitions

Answer 26

- Host: The organism from which a parasite obtains it’s nutrients - Definitive host (primary): The final host or host in which the parasite reaches sexual maturity - Intermediate host (secondary): Host in which a parasite passes through it’s larval or asexual stage - Accidental host: host other than the usual or normal host - Reservoir host: Host other than the normal host in which a parasite is capable of living and serving as a source of infestation - Vector: A carrier, usually an arthropod or insect, that transmits the causative agent of disease from infected to non-infected. Modes of transmission: * Direct (ingestion, skin penetration, inhalation, person-to-person) * Indirect (vectors, transplantation/transfusions) Single-host Parasites: only transmitted from human-to-human contact (oral-fecal) Multiple-host parasites: require 2 or more hosts to complete lifecycle * sexual parasite stage: definitive host * asexual/larval stage: intermediate host * can be limited to geographical area

Question 27

Protazoan Parasites

Answer 27

i. e. giardia - eukaryotic - trophozoites: active growing form - fragile - cysts: the dormant infective form; resilient

Question 28

Nematodes

Answer 28

Roundworms: * spindle-shaped * tough outer cuticle Organ systems: * muscular * nervous * reproductive * GI * parasatize the intestinal tract, blood and/or tissues - Sexes are separate

Question 29

Soil-transmitted Helminthiases (STH)

Answer 29

* 1.4 billion infected with Ascaris alone * Heaviest burden in 5-14 y/o * Most have concurrent infections * All linked to contaminated environment * Each species has separate signs & symptoms but overlapping themes: intestinal bleeding, malabsorption of nutrients, impaired growth, loss of appetite, diarrhea/dysentary, intestinal obstruction

Question 30

Platyheliminthes

Answer 30

- tape worms - flattened riboon shaped bodies - neck generates reproductive segments "proglottids" - no vascular or repsiratory systems

Question 31

FMT

Answer 31

the use of fecal microbiota to treat Clostridium difficile infections that are not responsive to standard therapies. Restoration of normal fecal microbiota Believed to work by bacterial interference & production of bacteriocidins