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Latency

-Ability of a pathogen to quietly exist inside a host -Usually causes persistent or recurrent disease -Examples: ▪Herpes viruses (intermittent flare-ups) ▪HIV (genetic hitchhikers) -Can confer protection from drug therapies

Airborne precautions

-Airborne infection isolation room (AIIR) -Specialized pressure systems -People entering AIIRs must wear air-purifying respirators ▪Examples: -Tuberculosis -Chickenpox -Measles

Invasins

-Allow pathogens to invade host tissues -Local-acting factors -Usually membrane-associated or secreted enzymes -Mechanism of action: ▪Break down host tissues ▪Form blood clots ▪Induce the host to uptake the pathogen ▪Motility

Integumentary system

-Based on overall weight and surface area is the largest body system -Consists of skin, hair, nails, and associated glands -Blocks most microbes ▪Pathogens have developed virulence factors that penetrate the integumentary system

Many bacteria and fungi also make extracellular enzymes

-Break down nutrients in the local environment -Allows pathogens to scavenge nutrients as they damage host tissues ▪Examples: Lipases - break down lipids Proteases - break down proteins

Agents that are transmitted from person to person and kill hosts quickly usually...

-Cause high-mortality outbreaks -Are short in duration -Are geographically isolated

Respiratory tract is the most common portal of entry

-Coughing and sneezing suspends pathogens in the air as respiratory droplets -Infectious agents stirred up from dust or soil ▪However, a pathogen that enters through the respiratory tract does not necessary establish an infection there

Virulence factors damage host cells by:

-Directly damaging host cells -Provoking dangerous immune responses

Viral pathogens generate cytopathic effects when they:

-Disrupt normal host cell function -Release from the host cell -Transform normal cells into cancer cells

Antigenic mimicry

-Emulating host molecules -Capsules can resemble host carbohydrates

The pathogen's reservoir could be:

-Environmental niche (e.g., soil or water) -An organism (e.g., humans or animals) -Fomites

Any route a pathogen uses to exit its host is a portal of exit

-Feces, urine, and bodily fluids such as blood or fluids drained from wounds, vomit, saliva, mucus, or semen ▪The portal of entry used by a pathogen is often the same as the portal of exit

Digestive system pathogens

-Frequently have a fecal-oral transmission -Invade the mucosal surfaces of the GI tract -Route of entry may be the first tissue affected, but it isn't necessarily the only tissue affected

Universal and standard precautions include:

-Hand washing before and after each patient contact -Change gloves between tasks or procedures -Barrier clothing and face shields or masks -Proper management of biosharps waste -Disinfection of surfaces, laundry and garments

Examples of Type I exotoxins

-Heat-stable enterotoxins made by enterotoxigenic E. coli -Superantigens ▪Pyrogens ▪Overstimulate the immune system to cause massive inflammation that harms the host ▪Staphylococcal enterotoxin causes food poisoning (membrane disrupting)

Intracellular pathogens

-Include viruses, many protozoans, and some bacterial pathogens -Spend a majority of their time inside host cells -Examples of intracellular bacteria include: ▪Listeria monocytogenes ▪Mycobacterium tuberculosis ▪Salmonella species

The immune system and/or antibiotics kill Gram-negative pathogens, which causes...

-Increases in circulating endotoxin levels -Leads symptoms to including fever, chills, body aches, hypotension, tachycardia, increased respiratory rate, inflammation, a feeling of disorientation, nausea, and vomiting

Even if a pathogen can't avoid immune detection, it could limit the immune system's actions by:

-Interfering with phagocytosis -Suppressing the immune response

Type III exotoxins

-Intracellular toxins -Bind to a receptor and enter the cell -Most exotoxins in this group are AB toxins ▪B (binding) region ▪A (active) portion exerts effects inside

Bacteria induce cytopathic effects as they:

-Invade host cells -Release toxins -Exploit host nutrients

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

Universal and standard precautions

-Limit transmission of blood-borne pathogens -All patients are treated as potential sources of bloodborne or other infectious agents -Handling precautions exist for all bodily fluids (e.g., blood, feces, non-intact skin, excretions, secretions except sweat)

LPS consists of:

-Lipid portion (Lipid A) -Sugars

Endotoxins enter from...

-Localized infections -Systemic infections -Gram-negative microbiota are introduced to areas where they don't belong -Surgery complications

Pathogens often become attenuated when grown in cell culture

-Lose virulence factors needed to cause disease -Still infectious but weakened -Do not cause disease in an immunocompetent host -Sometimes used in vaccines

In return for a place to live, some of our microbiota...

-Manufacture vitamins for us -Compete with potential pathogens -Promote immune system maturation ▪These microbes have mutualistic relations with us ▪Disrupting normal microbiota balance can compromise a patient's health

Type I exotoxins

-Membrane-acting extracellular toxins -Bind to target via receptors on the surface -Propagate a signaling cascade via the receptor -Evokes changes in gene expression -Leads to diverse outcomes ▪Range from temporarily altered cell physiology to cell death

Type II exotoxins

-Membrane-damaging toxins -Disrupt the host cell plasma membrane -Forms pores or removes phosphate head groups from phospholipids -Destabilizes the membrane -Cause cell lysis

Contact precautions

-Minimize transmission of infectious agents spread by fomites and healthcare workers -Barrier gowns and gloves worn -Disinfection practices increase -Patient transport is limited -Noncritical equipment dedicated for single-patient use -Examples: MRSA and C. difficile

Virulence factors are often logically linked to transmission

-Most STI associated pathogens evolve virulence factors that allow them to be infectious but minimally symptomatic

The immune system recognizes our normal microbiota's presence

-Mounts a moderate response to it -Normally a balanced communication between our immune system and resident microbes

Exotoxins are named based on the organism that makes it or the type of cells it targets

-Neurotoxins - affect the nervous system -Enterotoxins - target the GI tract -Hepatotoxins - affect the liver -Nephrotoxins - damage the kidneys ▪To date, >200 exotoxins have been described ▪Exotoxins are often classified into three main families based on their mode of action

Treating lipid-based endotoxins...

-Not readily neutralized -No vaccines to protect against them ▪Necessary to ensure that endotoxins don't contaminate anything used in patient care (e.g., drugs, implanted devices, etc.)

Infectious dose-50 (ID50)

-Number of cells or virions needed to establish an infection in 50% of exposed hosts -More infectious pathogens have a lower ID50 ▪Just because a pathogen is highly infectious doesn't mean it is especially dangerous -For a pathogen to establish disease it must first infect the host

Third, a pathogen must invade tissues and obtain nutrients

-Once a pathogen enters the host and adheres to tissues, it must obtain nutrients ▪Following adhesion, the pathogen has several options: -Stay on the surface of the host cell -Pass through cells to invade deeper tissues -Enter cells to reside as an intracellular pathogen ▪As pathogens invade, they tend to damage host tissues and generate cytopathic effects

Pathogens get in through....

-Otic entry -Abrasions -Physically boring through skin -Invade the conjunctiva -Bites -Cuts -Injections -Surgical incisions

Immune suppression

-Pathogens suppress immune function by: ▪Directly targeting immune system cells ▪Making proteases that break down host antibodies ▪Interfering with transcription of interleukins ▪Interfering with the molecular signaling that activates parts of the immune response

Antigenic variation

-Periodically altering the surface molecules -Prevents a rapid immune response ▪Causes include: -Mutations in the genome -Change in protein expression

Interference of phagocytosis

-Phagocytes engulf and then destroy pathogens with hydrolytic enzymes -Some pathogens avoid phagocytosis by: ▪Making a capsule ▪Bursting free of the phagosome ▪Blocking fusion of the phagosome with the lysosome ▪Neutralizing enzymes of the phagocytes ▪Damaging phagocytic cells using toxins -Pathogen may have evolved to thrive inside the harsh environment of the phagolysosome

Transmission precautions

-Prevent direct contact, droplet, and airborne disease transmission -Apply when a specific infectious agent is suspected or known to be present -Signage is posted to inform healthcare providers and visitors of necessary precautions

Droplet precautions

-Procedural mask when in the patient's room -Limit patient transport -During transport the patient wears a mask ▪Example: -Rubella -Influenza -Pertussis

ID50 and LD50 can change based on:

-Species affected -Host's immune fitness -Route of exposure ▪Note: LD50 and ID50 measures usually come from animal studies, so they are not a perfect predictor of what would occur in people

Most healthcare facilities have an infection control team that strives to limit infection risks for healthcare workers and patients

-Standard precautions -Transmission precautions

Exotoxins

-Toxic -Soluble proteins -Affect a wide range of cells -Made by both Gram-positive and Gram-negative bacteria

Antigenic masking

-Upon entering the host, the pathogen may conceal antigenic features -Coats itself with host molecules

To establish an infection, a successful pathogen must complete five general tasks:

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

safely replicate

A pathogen must evade the immune system so it can...

Lethal dose-50 (LD50)

Amount of toxin needed to kill 50% of affected hosts that are not treated

Pathogens can damage host cells and generate CYTOPATHIC EFFECTS

Cytocidal - kill the cell Noncytocidal - damage the cell

Type 3 toxins (A-B toxins)

DIPHTHERIA TOXIN - Cytotoxin that blocks protein synthesis BOTULINUM TOXIN - Neurotoxin causes flaccid paralysis TETANUS TOXIN - Neurotoxin causes contractile paralysis (lock jaw) VIBRIO TOXIN - Enterotoxin cholera induces watery diarrhea

Two classes of toxins:

Endotoxins Exotoxins

Toxigenic

microbes that make toxins

Dysbiosis:

microbiota disruption ▪Examples: -Course of antibiotics kills off normal microbiota in the gut -Allows Clostridium difficile (usually present in small numbers in the intestines) to suddenly flourish and cause disease

Toxins:

molecules that generate a range of adverse host effects such as tissue damage and suppressed immune response

Tropism:

preference of a pathogen for a specific host (and even a specific tissue within the host) ▪All microbes typically require specific host features to establish infection ▪Most microbes exhibit some level of tropism, but this factor can change over time ▪Most emerging pathogens expanded host or tissue range to become able to infect humans ▪Even when a pathogen successfully invades its preferred host and makes its way to its favored tissue, that doesn't necessarily mean it will cause disease ▪Many host factors, from age and gender to overall health and life habits, impact whether disease develops

Toxemia:

toxins in the bloodstream

Virulence factors:

ways pathogens overcome our defenses (e.g., features that help microbes adhere to host cells, invade host tissues, etc.)

Second, a pathogen must adhere to host tissues

▪After entering a host, the pathogen must next adhere to host tissues ▪Initial adhesion is often nonspecific, such as through hydrophobic interactions ▪After nonspecific anchoring, the agent may target an exact surface molecule on the host cell ▪Species and tissue tropism is due to specificity for a particular host cell surface marker

There are four biosafety levels:

▪BSL-1 ▪BSL-2 ▪BSL-3 ▪BSL-4

Biofilms and Quorum Sensing

▪Bacteria form BIOFILMS on almost any natural or manmade surface ▪According to the NIH, 60-80% of human infections originate from biofilms

Host-microbe interactions influence virulence

▪Classic virulence factors include pathogen toxicity, aggressiveness, and transmission ▪Virulence is also associated with host properties (e.g. immune fitness, normal microbiota balance) ▪Pathogens develop new virulence factors in response to the host and selective pressures

Biosafety levels dictate appropriate on-the-job behaviors in healthcare

▪Healthcare and laboratory personnel regularly come in close proximity with biological hazards ▪Not all agents present the same level of danger

Virulent versus Attenuated Pathogens

▪Making virulence factors requires an energy investment ▪Pathogens only develop and keep a particular virulence factor when it bestows a benefit ▪Environment heavily influences production of virulence factors

Tools to Obtain Nutrients: Siderophores and Extracellular Enzymes

▪Most cellular pathogens require iron to survive ▪In humans, very little iron freely circulates in tissues and blood -Transferrin binds to iron and shuttles it to tissues ▪Many bacteria produce siderophores that snatch iron from transferrin

Urogenital Tract and Transplacental Entry

▪Most sexually transmitted pathogens enter through the mucosal lining of the vagina or cervix in women or the urethra in men ▪Certain sexually transmitted pathogens invade through the skin of the genitalia ▪Pathogens that cause urinary tract infections invade the urethra in men and women ▪Some pathogens exhibit vertical transmission by transplacental entry

Common places for healthcare-acquired biofilm formation include:

Implanted devices (e.g., catheters, implanted prosthetic joints) Rocky deposits in the kidneys (kidney stones) or gallbladder (gallstones)

Sometimes the symptoms a pathogen generates facilitate transmission to others

Itchiness Sneezing Coughing Diarrhea

If present in sufficient quantities, ENDOTOXIN causes septic shock

May kill the host as organs fail In the U.S., septic shock affects 1 million people per year (deadly in up ½ of cases)

diseases of portal of entry

OTIC - P. Aeruginosa SKIN - S. Aureus URINARY- E.Coli TRANSPLACENTAL - HIV & Toxoplasmosis G.I. TRACT - Cholera, Salmonella RESPIRATORY- Measles, Influenza PARENTERAL - Hepatitis

transmission to a new host

The last crucial step in a pathogen's success is

Lipid A region of LPS is called endotoxin

Toxic to us and other animals -Mainly released when Gram-negative bacteria die

Pathogenicity:

ability of a microbe to cause disease

Portal of entry:

any site that a pathogen uses to enter the host -Mucous membranes are the most common portal of entry -Site where disease develops (but not necessarily the only or the main site affected) -Some pathogens have >1 portals of entry

Opportunistic pathogens

are agents of disease under certain circumstances ▪Examples: -Escherichia coli in the appendix enters the abdominal cavity -Weakened immune system allows yeast infections

Adhesins (adhesion factors)

are virulence factors used to stick to host cells in a specific or nonspecific manner -Bacterial adhesins include cell wall components, capsules, fimbriae and pili, a variety of plasma membrane-associated molecules

Normal microbiota

colonize our skin, areas of the digestive, genital, urinary, and respiratory systems

Virulence:

describes the degree or extent of disease that a pathogen causes

Pathogens:

disease-causing microbes ▪Pathogen have adaptations that allow them to interact with certain host tissues -Dangerous to the host

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

Examples: -Tissue damage that develops in tuberculosis is due to the immune system attacking cells infected with the bacteria -Most viral infections result in the immune system killing virus-infected cells

Due to differences in host factors, a harmless species of the normal microbiota in one host may be pathogenic in another

For example: -Group B streptococci (GBS) infections ~30% of women harbor GBS as normal commensals in the vagina -Associated with sepsis, meningitis, and pneumonia in newborns -Pregnant women are screened for GBS

Lipopolysaccharide (LPS)

Gram-negative bacteria have an outer membrane rich in ....

what does it make viruses, fungi, protozoa, algae and helminths pathogenic?

VIRUSES - cause cytopathic effects FUNGI - produces toxins like spores PROTOZOANS & HELMINTHS- The mere presence will damage tissue ALGAE - Produces toxins

Endotoxemia:

endotoxin in the bloodstream