MIC 301 Exam 3

Commensal

microbiota colonize a host in a typically non-harmful coexistence (benign)

Mutalistic

both benefit (i.e., vitamin production, immune system modulation, barrier against pathogens, nutrition, habitat)

Pathogenic

capable of causing disease

Positive effects of host-microbiome symbiosis

confers resistance to colonization by pathogens
-regulates the cardiovascular system
-supports host defense functions
-has anti-inflammatory properties
-provides additional metabolic potential
-has antioxidant activity
-maintains a healthy digestive tract

normal human microbiota (aka normal flora)

resident colonizing microbes (commensals) of our skin, respiratory, genitourinary, and digest system

-develops, expands, and evolves throughout life and plays a critical role in human health

-modified by many factors and has a close relationship with physiologic functions and development of diseases in different systems

The b acteria in our microbiomes are essential to human health and aid in biological processes such as:

extracting energy from food
-providing essential vitamins
-regulating our immune system
-regulating our glucose levels and metabolism
-protecting us against disease-causing microbes

Dysbiosis

disruption of normal microbiota balance that can compromise health

-increase risk for infections and disease

the immune system recognizes and responds to our normal microbiota

this defense system is critical to protect us from infection and disease

-our microbiota is critical for training our immune system

-childhood exposure to a variety of microorganisms is necessary for proper immune system development

Dysbiosis of the oral microbiome

can lead to periodontal disease

Pathogenicity

the ability of a microbe to infect a host and/or cause disease/damage

-host damage results from host-pathogen interactions

virulence

degree or extent of disease/damage that a pathogen causes (disease severity) or the ability of the pathogen to multiply within the host (pathogen's infectivity)

Host-Microbe Interactions

influence pathogenicity and virulence

-host properties (e.g., immune fitness, normal microbiota balance) combined with pathogenicity of the microorganism (virulence factors)

Virulence factors

mechanisms used by pathogens and/or components they produce to: infect, invade, damage host tissues, overcome defenses, or achieve transmission to a new host

-pathogens develop new virulence factors in response to the host and selective pressures

For a pathogen to persist in a population...

-it must endure over time
-it must find a balance between breaking down defenses and living within an individual host
-it must get readily transmitted to a new host

Pathogens that kill hosts quickly usually..

- cause high-mortality outbreaks
- are geographically isolated
- are short-lived in duration or in a host/population

The goal of being a successful pathogen...

is to get transmitted to a new host to continue your life cycle

Making virulence factors requires

an energy investment

-pathogens only benefit/maintain a particular virulence factor when it bestows a benefit

The enviornment heavily influences?

production of virulence factors

Pathogens often become attenuated when grown in the lab

lose virulence factors needed to cause disease
-still infectious but weakened
-do not cause disease in an immunocompetent host
-sometimes used in vaccines

Examples of bacterial virulence factors

avoidance and/or inhibition of the host's immune response
-entry into and exit out of host cells and/or tissues
-substances produced by or derived from microbes that have adverse host effects
-attachment of host cells; includes colonization of host
-obtained from the host for viability and multiplication

toxins

promote infection and disease by directly damaging host tissue or by disabling the immune system

toxigenic

microbes that make toxins

toxemia

toxins in the bloodstream

endotoxins

lipid A portion of LPS within the Gram-negative bacterial outer membrane; released upon cell lysis; inflammatory

Exotoxins

proteins (often enzymes) produced and actively secreted by growing cells; active in low concentrations

septic shock

characterized by fever, chills, fatigue, malaise, tachycardia, and hypotension
-causes life-threatening drop in blood pressure and multiorgan failure
-in the U.S., affects - 1 million people per year (fatal up to 1/2 of cases)

Endotoxins treatment issues

lipid-based endotoxins, not readily neutralized
-no vaccines to prevent/protect available
-appropriate antibiotic therapy is critical

type 1: membrane-acting extracellular toxins

the toxin binds at the host plasma membrane to generate a signal that changes host cell gene expression
-Toxin does not enter cell

Type II membrane damaging toxins

toxins disrupt host cell membranes by forming pores or breaking down membrane lipids
-results in cell lysis

Type III:
Intracellular toxins

binding portion (B) of the toxin binds to the plasma membrane
-toxin enters cell, often by endocytosis
-active portion (A) enters the host cell and exerts an effect

For a pathogen to establish disease it must first

infect the host

Infectious dose-50 (ID50)

number of pathogens needed to establish an infection in 50% of exposed hosts
-more infectious pathogens have a lower ID50
-HOWEVER: highly infectious does not equal especially dangerous

Lethal dose-50 (LD50)

amount of toxin needed to kill 50% of affected hosts that are not treated
-lower LD50= higher virulence

ID50 and LD50 can change based on:

-species affected
-host's immune fitness
-route of exposure

Five steps to infection

1. enter the host
2. adhere to host tissues
3. invade tissues and obtain nutrients
4. replicate while warding off immune defenses
5. transmit to a new host

portal of entry

any site that a pathogen uses to enter the host

-determined by the mode of transmission
-mucous membranes are the most common portal of entry
-maybe site where disease develops (but not necessarily)
-some pathogens have >1 portals of entry

Respiratory Mucosa (including ocular)

most common portal of entry
-microbes transmitted by CONTACT with mucosa of mouth/eyes/nose or INHALATION of respiratory droplets, aerosols, or dust particles

Skin

largest body system
-physical protective barrie
-has to be penetrated for infection to occur

GI mucosa

infections frequently due to fecal-oral transmission via contaminated food, water, or fingers
- disease may occur elsewhere

Urogenital systems

most STIs are acquired thru mucosa; some through the skin
-urinary tract infections often normal flora

parental

introduced directly into bloodstream intravenously or by injection

Transplacental

some pathogens exhibit vertical transmission
- spread from mother to developing child in utero

Attachment between pathogen and host dependent on:

Surface molecules on pathogens termed adhesions that bind to specific surface receptors on certain host cells
-pili
-species and tissue tropism

Pili (fimbriae)

bacterial adhesins that assemble into hair-like appendages and extend from the cell surface; other adhesins are directly associated with the microbial cell surface

Species and tropisms

due to specificity for attachment to a particular host cell surface marker

tropism

Preference of a pathogen for a specific host and/or a specific tissue within the host
-Most microbes exhibit some level of tropism, but this factor can change over time
-Pathogenic microbes require specific host/microbial features to interact with certain host tissues and establish an infection
-Many host factors (i.e., age, gender, overall health, life habits) impact whether infection and/or disease develops

Adherence is Critical for Infection

if adhesins and/or receptors can be altered or masked to interfere with attachment, infection (and therefore disease) can be prevented or controlled

Bacteria alternate between two distinct life phases:

Planktonic (free-floating)
-biofilm-associated (multicellular communities of attached sessile cells)

Planktonic bacterial attachment and colonization of surfaces is critical during

the development of a sustainable, persistent population within a mature biofilm

Biofilms

are cooperative communities of adherent microbes encased in a protective, sticky, slimy, matrix layer

-Multiple layers develop; residents of the innermost layers are highly protected
- Can form on almost any surface, especially prevalent in aqueous enviroments
- Share nutrients, protected from environmental stressors

Microbes within the biofilm periodically detach and are released as free-growing planktonic cells;

results in recurrence of disease and/or spread to new areas to begin process again

EPS matrix

contains a wide variety of polysaccharides, proteins, glycoproteins,
glycolipids, extracellular DNA (eDNA) of microbial origin

Quorum Sensing (QS)

cell-to-cell chemical communication system allowing microbes encased within the biofilm to coordinate activities/alter gene expression to benefit the community

Biofilms are important factors affecting human health

~ 90% of human bacterial/fungal infections originate from biofilms
- Microbes resident in biofilms are >1000X more resistant to antibiotics and disinfectants

Biofilm formation is linked

treatment-refractory infections as well as persistent, recurrent, and chronic infections

-bacteria and yeast adhere to damaged tissues and implant medical devices

Invasins

Membrane-associatedorsecreted enzyme virulence factors that function to assist microbial invasion

-Actlocallytodamagehostcells&/or have immediate effect of facilitating the growth and spread of the pathogen

most cellular pathogens require ___ to survive

iron

-Little iron freely circulates in host tissues/blood
- To acquire/remove iron from host iron transport proteins (transferrin, lactoferrin, heme, etc.) bacteria produce:
a) Membrane bound iron-binding proteins &/or
b) Secreted iron-binding siderophores

Many bacteria and fungi also make

extracellular enzymes

-break down nutrients in the local environment
-allow pathogens to scavenge nutrients as they damage host tissues

Lipases

break down lipids

Proteases

break down proteins

nucleases

break down nucleic acids

cytopathic effects

As pathogens establish an infection and/or invade, death or damage occurs to host cells and tissues

cellular pathogens

Induce cytopathic effects as they
-invade host cells,
-release toxins,
-exploit host nutrients

Viral pathogens

generate cytopathic effects when they
-disrupt normal host cell function
-release from the host cell
-transform normal cells into cancer cells

The immune system

also inflicts damage on the body as a by-product of fighting infections

e.g.; intracellular infections result in the immune system killing of pathogen-infected host cells
- Damage from chronic inflammation due to chronic infection

A pathogen must evade host immune defenses

The host has evolved mechanisms to fight infections; pathogens have countermeasures to escape host defenses. Back-and-forth battle.

-A pathogen must evade the defenses of the immune system so it can replicate (and achieve transmission to the next host) - "tug of war"

antigen masking

pathogen covered in host factors to avoid immune detection

antigen mimicry

pathogen's antigens resemble host molecules, helping it evade immune detection

antigen variation

pathogen switches its antigens, thwarting the mounting immune response

intracellular pathogens

-include viruses, many protozoans, and some bacterial pathogens
-spend a majority of their time inside host cells

Latency

The ability of a pathogen to remain dormant; stay "under the radar"
-Usually causes a persistent or recurrent disease; "strike and retreat"
-Can confer protection from drug therapies (usually target replication)

suppressing immune response

Target immune cells directly to disrupt function
- Make proteases to break down immune effectors like antibodies
- Interfere with signals and factors that activate specific immune responses

reservoir

habitat where pathogen is typically found

Animate or inanimate source when pathogen is normally lives and reproduces (human, non-human animal, plant, environmental niche, fomite)
- Identification useful in preventing disease and stopping large outbreaks
+Control disease by eliminating/protecting against exposure to pathogen's reservoir

Human to human

STIs
-measles, polio, smallpox
-respiratory pathogens

Animal to Human

plague (rat, rat flea)
-ebola (bats, monkeys)
-rabies

Environment to human

Chlorea, V. vulnificans (water )
-tetanus (soil)
-legionnaire's disease (water)

Portal of exit

any route a pathogen uses to exit its host
-maybe the same as the portal of entry; not always

-often the infectious symptoms (or lack of) a pathogen generates facilitate transmission

-bodily fluids produced during an illness are often rich in infectious pathogens

Biosafety levels (BSL) 1-4

are based on numerous criteria, with the following key considerations:
- Level of infectivity
- Extent of disease caused and mortality rates
- Mode of transmission
- Availability of preventions and treatments

BSL 1 & 2

most laboratories, hospitals, health care settings

BSL 3 and 4

restricted to approved clinical/research facilities

Standard Precautions

designed to limit transmission of pathogens

-All patients are treated as potential sources of infectious agents
- Handling precautions exist for all patient samples to prevent the potential transmission of infections
§ All bodily fluids, excretions, & secretions (e.g., blood, urine, feces, vomit, mucous, pus, discharge)
§ All bodily tissues; includes breached skin (rashes, wounds) and mucous membranes

universal/standard precautions in all health care facilities

Hand washing before and after each patient contact
- Wear gloves and change gloves between tasks or procedures
- Barrier clothing and face shields or masks (PPE) as needed
- Proper management of biosharps waste
- Disinfection of surfaces, equipment, laundry and garments
- Receive proper training and periodic retraining on all procedures

transmission precautions

Used in addition to Standard Precautions for patients infected with certain infectious agents for which additional precautions are needed to prevent infection transmission by fomites and/or health care workers.
- 3 main types - contact, droplet, and airborne disease - one/multiple implemented dependent on the specific infectious agent

contact precautions

wound/skin infections
-resistant infections
-infectious diarrhea

-limit patient transport, special attention to hand washing, gloves at all times, gown at all times, increased disinfection; single-use patient equipment

Droplet precautions

respiratory infections
-coughing, sneezing
-IAV, pertussis, meningitis

-limit patient contact, surgical mask at all times

Airborne precautions

tuberculosis, rubeola (measles), Covid-19

-limit patient transport, air-purifying (N95 respirator), place patient in AIIR facility

immune response

a physiological process coordinated by the immune system to eliminate antigens

immune

specific protection conferred by the adaptive immune responses

susceptible

not immune to a given pathogen and it may cause infection

innate immunity

inborn, ancient protection existing in one form or another in all eukaryotic organisms
-Generalized responses
-Non-specific immunity

Adaptive immunity

Only in vertebrate animals
-Matures over time
-Responses tailor to pathogens
-Typically requires 4-7 days to fully activate
-Exhibits memory

What are the benefits of our normal microbiota?

compete for nutrients with pathogens
-compete for space with pathogens
-make substances that may directly damage pathogens
-generate an environment that limits pathogen survival

First line of defense

aim to prevent pathogen entry

Mechanical barriers

rinse, flush, or trap pathogens to limit their spread into the body

Mechanical barrier examples

Tears washing debris/pathogens from eyes
-Urine flushing microbes out of the body
-Saliva limits what microbes adhere
-Mucus membranes trap microbes-line all body entrances as well as the stomach, intestines, lungs, and bladder
-Mucociliary escalator sweeps away from the lungs and toward the mouth by ciliated cells

mucociliary escalator

sweeps away from the lungs and toward the mouth by ciliated cells

Chemical barriers

may directly attack invaders or establish environments that limit pathogen survival in or on a particular tissue

Chemical barrier examples

Lysozymes
-Hydrochloric acid in the stomach
-Skin is relatively dry, salty, and slightly acidic
-Fatty acids in sweat and earwax

Lysozyme

found in secretion (e.g., tears, breast milk) and breaks down bacterial cell walls (does nothing against viruses or fungi)

antimicrobial proteins (AMPs)

Proteins that destroy a wide spectrum of viruses, parasites, bacteria, and fungi
-So far, more than 880 have been found!
-Rare for microbes to develop resistance against AMPs