bacteriology 2+3 (host-pathogen-enviornment)

Host-pathogen-environment interaction

Disease results from the interplay of host, pathogen, and environment (overlap of all three = disease)

Rain scald/rain rot example

Cattle/horses (susceptible host) + Dermatophilus congolensis (from contaminated environment) + rain (skin maceration lets bacteria invade) = exudative dermatitis on the top-line

Factors making a host susceptible

Genetic predisposition/epigenetics, comorbidities (immunocompromised vs immunocompetent), concurrent medication, barrier breakdown (dysbiosis), age, nutrition, stress

Age and susceptibility

Immature immune system in young patients; immunosenescence in aged patients

Pyoderma example (host focus)

Dog on immunosuppressive drugs for allergic dermatitis + seasonal allergy flare allows overgrowth of Staphylococcus pseudintermedius (past normal flora) = bacterial pyoderma

What makes a microbe a pathogen

Can be opportunistic (from environment or host), virulence of the microbe, burden (exposure level), and ability to reach its preferred site of infection (dysbiosis, iatrogenic infections)

Virulence vs host compromise

Low virulence requires host compromise or high exposure; high virulence can cause disease in an immunocompetent animal even at low exposure

Burden (pathogen)

Exposure level (high vs low) can change disease outcome; usually affected by the environment and sometimes host susceptibility

Pathogenic E. coli calf diarrhea example

Naïve calf gut microbiome + virulent E. coli with specific virulence factors (past normal flora) + poor hygiene/contaminated pens = diarrhea; commensal E. coli do not cause disease

Environmental factors affecting disease

Weather, climate change, contaminated food/water, shipping animals to new locations, contact with wildlife or other domestic species, husbandry, geographic exposure

Weather and pathogens

Wet seasons can lead to overgrowth of pathogens; dry seasons can lead to dissemination of pathogens

Climate change and disease

Alters microbial growth and vector abundance

Geographic exposure

Not all veterinary pathogens are in the US, and different pathogens are distributed across the US

Chlamydia felis environment example

Young cat (susceptible) + C. felis spread by direct contact with infected ocular secretions + multi-cat shelter/cattery (close contact) = conjunctivitis

Microbiome

Community of microorganisms (bacteria, fungi, viruses) living together in a particular habitat; environments have microbiomes too

Normal flora and microbiome

Microbes that are part of the microbiome are considered normal flora; depends highly on location and on host species

Commensal

Organism that lives in/on a host without causing disease; most bacteria normally in the intestine, on skin, and on mucous membranes; can also be symbiotic

Pathogen

Microorganism capable of causing disease in a susceptible host; does not always cause disease

Pathogens and normal flora vs carrier state

Pathogens may be part of normal flora (present in MOST animals in a population) or live in only a proportion of animals (= carrier state)

Normal flora / opportunistic infection

Bacteria normally found in healthy animals at particular sites; cause disease when host defenses are compromised or they enter normally sterile sites; widespread and impractical to eliminate (e.g., Streptococcus equi subsp. zooepidemicus in equine upper respiratory tract)

Carrier state

Animal harbors a specific pathogen without necessarily showing clinical disease; may shed and transmit to susceptible animals; identifying/managing carriers is critical to controlling contagious pathogens (e.g., S. equi subsp. equi in asymptomatic horses after strangles)

Nonsterile sites (normal flora)

Gastrointestinal tract, lower urogenital tract, upper respiratory tract, skin, oral cavity, external ear and ocular surface (conjunctiva)

Sterile sites

Blood, cerebrospinal fluid, bone, brain, heart, liver, and spleen

Clinical importance of sterile sites

Bacteria recovered from a normally sterile site may indicate infection; contamination during sample collection must also be considered

Colonization

Presence and growth of bacteria at a body site without necessarily causing disease

Infection

Organisms establish themselves within a host and may result in tissue injury or host response; not all infections produce clinical signs

Primary (true/obligate) pathogen

Can cause disease in otherwise healthy hosts

Opportunistic pathogen

Typically requires altered host defenses or access to susceptible tissues to cause disease

Endogenous infection

Arises from bacteria living on the host (skin, mucous membranes, GI tract), i.e., commensals

Exogenous infection

Arises from external sources (contaminated food/water, contact with an infected individual); tends to be environmental (e.g., Aspergillus)

Nosocomial infection

Hospital-acquired infection; can carry higher incidence of antimicrobial resistance

Pathogenicity

Capacity of a bacterium to produce disease in a host; qualitative term (all or none)

Virulence

Degree of pathogenicity (disease-producing power) at a particular infection site within a particular host species; quantifies pathogenicity

Factors that change virulence

Number of infecting organisms, host defense, and individual virulence factors; varies by genus, species, strain, and infection site (e.g., some E. coli strains are virulent only in the intestine)

Highly virulent pathogen

Can cause disease with few bacteria and/or little host tissue compromise

Weakly virulent pathogen

Needs many bacteria and/or a lot of host tissue compromise to cause disease

Predisposing factors to infection

Tissue damage (trauma, burns, wounds, surgery), impaired host defense, introduction of microbes to sites where they are not normally found, disturbance of normal flora (antibiotics, nutrition)

Main cause of opportunistic infections

Impairment of host defense (from comorbidities, some medications, age)

First line of defense

Nonspecific: microbiome/normal flora, skin (physical barrier), chemical barriers (sweat, sebum, tears); prevents most pathogens from establishing infection

Second line of defense

Nonspecific cellular barrier/innate immune system (neutrophils, macrophages, dendritic cells)

Third line of defense

Specific cellular barrier/adaptive immunity (T and B cells, antibody)

Innate immunity

Immediate/fast response; no memory; prevents most potential pathogens from establishing infection; key cells are neutrophils, macrophages, dendritic cells

Adaptive (specific) immunity

Takes days to weeks to develop; highly antigen-specific; has memory (strong secondary response on re-exposure); key cells are lymphocytes (T and B cells)

Innate defense components

Skin (physical), mucus/mucous membranes, phagocytes (macrophages/RES, neutrophils/PMNs), natural resistance of tissues, inflammatory response including fever

Antibody-mediated immunity (AMI)

Destruction of extracellular bacteria via lysis, opsonization and phagocytosis, and toxin neutralization

Cell-mediated immunity (CMI)

Activates macrophages to control intracellular bacteria and cytotoxic T cells to eliminate infected host cells

Bridge between innate and adaptive immunity

Dendritic cells

Internal host stressors

Species, sex (pregnancy), age (very young/very old), endocrine changes, immunosuppression

External host stressors

Extremes of temperature, nutritional deficiencies, overcrowding, transportation, change in feed, weaning

Why identify predisposing factors

Must be identified in every case of infection to properly treat and control disease

Horizontal transmission

Between animals/individuals of the same generation: direct contact (incl. sexual), respiratory droplets or airborne particles, indirect contact via fomites/food/water, vector-borne

Vertical transmission

Dam to offspring: transplacental, exposure during birth, or through milk

Contagious infection

Infection transmissible from one animal to another, directly or indirectly

Fomite

Contaminated intermediate object that transmits a pathogen by indirect contact

Vector

Any living creature that can pass an infection to another living creature; tend to be arthropods (insects, ticks, mites, fleas)

Reservoir

Supply of a pathogen; typically another animal (birds, rodents, other wildlife)

Amplifying host

Allows a pathogen to replicate rapidly and in high concentrations

Dead-end (incidental) host

Does not develop sufficient pathogen levels to transmit to an insect vector

Bridge vector

Acquires pathogen from an infected wild animal and then transmits it to a human or secondary host

Enzootic (sylvatic/jungle) cycle

Transmission between reservoir hosts and primary/enzootic insect vectors; reservoirs maintain the pathogen, often without severe disease

Epizootic (rural) cycle

Transmission between domestic animals (amplifying hosts) and primary/accessory insect vectors; amplifying host has enough pathogen that a vector will probably become infectious during a blood meal

Urban cycle

Humans are the source of infection with enough pathogen for vectors to become infected and amplify within the human population

Outbreak

Unexpected increase in disease cases within a defined population or location (e.g., farm, herd, hospital)

Epidemic

Increase in disease cases above what is normally expected in a particular population or geographic area

Endemic

Disease consistently present at an expected baseline level within a particular population or region

Pandemic

Epidemic that spreads across multiple countries or continents, affecting large populations

Four traits of a "good" pathogen

Attach and colonize, invade/gain access to the body, evade host innate defenses, produce molecules that cause dysfunction or damage (lysis); all modulated by virulence factors

Adhesins

Virulence factors used for colonization; bacteria-specific and tend to determine infection location (e.g., E. coli fimbriae/pili attach to bladder and GI epithelial cells)

Invasins

Virulence factors that let bacteria enter host cells or invade tissues; some are enzymes that break down host tissue and facilitate spread

Invasin examples

Salmonella invasion-associated proteins enter intestinal epithelial cells; some Streptococcus species produce hyaluronidases and fibrinolysins that facilitate tissue spread

Capsule (immune evasion)

Protects against host defenses: prevents/reduces phagocytosis, interferes with complement deposition and opsonization, shields surface antigens from immune recognition; mostly polysaccharide, some protein

Biofilms (immune evasion)

Shield bacteria from the host immune response

Obligate intracellular parasite

Requires host cells for replication, although infectious forms may survive extracellularly (e.g., Chlamydia)

Facultative intracellular parasite

Invades cells but does not require an intracellular environment for growth (e.g., Listeria monocytogenes, Salmonella)

Antigenic variation

Ability of an organism to systematically alter proteins displayed to the host immune system, creating a constantly changing population that is hard to eliminate (e.g., Borrelia burgdorferi)

Phase variation

On-off expression of a particular antigen

Antigenic variation vs phase variation

Antigenic variation = expression of alternative forms of an antigen; phase variation = on-off expression of an antigen

Superantigens

Antigens that cause excessive, nonspecific T-cell activation and massive cytokine release; can activate up to 20% of T cells vs <0.001% for normal antigens

Superantigen effects

Nonspecific T-cell response impairs adaptive immunity; T cells release large IFNγ, activating macrophages to overproduce IL-1β, IL-6, and TNFα; can cause shock and multiple organ failure

Endotoxin (LPS)

Gram-negative outer membrane component; lipid A causes most endotoxic activity; released during growth or lysis; recognized by CD14/TLR4/MD-2; excess activation causes TNF-α, IL-1β, IL-6 release, septic shock, and multiple organ dysfunction

Exotoxins

Protein toxins from gram-positive and gram-negative bacteria; most heat-labile (some heat-stable); localized or systemic effects; classified as neurotoxins, enterotoxins, cytotoxins

Siderophores

Iron-binding molecules synthesized when iron is absent; bind iron with very high affinity so bacteria can compete with host transferrin and lactoferrin

Host iron withholding

Iron in blood is bound to hemoglobin (erythrocytes) or transferrin (plasma); iron in milk and secretions (tears, saliva, bronchial mucus, bile, GI fluid) is bound to lactoferrin

Bacterial iron requirement

Most bacteria require iron for growth and scavenge it from the host using siderophores