Microbio Final Exam

one health

interconnection and shared environment, people, animals, and the environment

historical development of one health: Edward Jenner

• pus from cowpox - inculate 8 year old - 1st vaccination against smallpox - used cowpox to protect agaisnt smallpox

rudolf virchow

zoonosis term

rober Koch

• kochs postulate

• anthrax

Louis pasteur

• pasteurization

• live attenuated vaccines

animals and one health

• wild animals are natural reservoirs

intermediate host

• pathogens life stages and adaptation

transmission

• airborne and contamination

salmonella case

• host restricted was worse than the host adapted

spread

• confinement

• less genetic diversity

• pathogens spread

CAFO

• confined animal feeding operations

• antibiotic use

• less diversity

• more stress impacts the gut health

• intensive animal systems close contact

• weak microbial network to fight diseases

microbiome

AMR reservoir

drivers of disease emergence

• climate change

• CAFOS

• global connectivity

• biodiveristy loss

• microbial evolution

improvements

• manure management

• cross border surveillance

intrinsic

• structural barrier - outer membrane of bacteria

acquired

• HGT resistance genes

• mutations

adaptive

• biofilms create niche for acquired HGT due to close contact easier for conjugation to happen

when and how are antibiotics used

• prophylaxis

• metaphylaxis

• growth promotion

prophylaxis

• prevention

• given to healthy animals to prevent infection

• example and animal about to undergo surgery

metaphylaxis

control

• given to an entire group when infection is detected in the herd

genetics - MGEs

• MGEs mobile genetic elements: plasmids, transposons, integrons - share resitance genes

co-selection

• exposed to heavy metals, biocides, and urban pollutants

cross resistance

• single mutation

alternatives to AMR

• fecal transplant

• probiotics

• CRISPR Cas

pathogen

• a microorganism that can cause disease (host damage)

pathogenicity

• the ability of a microorganism to cause disease

virulence

• the relative ability of a pathogen to cause diesase

• severity or degree of disease caused

virulence factor

• any trait that enhances the ability of an organims to cause disease

• toxins, capsules, enzymes

• biofilm formation

strategies pathogens use to cause host damage

• invasion - phili fimbrae attach to host cells

• exotoxins

• endotoxins

• immune evasion

exotoxins

• toxins excreted by bacteria that target specific host sites

• exmaple AB toxins and cytolytic toxins

endotoxins

• lipid A portion of LPS in gram neg bacteria - triggers inflammatory response

immune evasion

• use capsules to avoid phagocytosis

E coli

• attaches tighlty to the gut mucosa via intimin

• shiga toxins

good bacteria

• nutrient competition: microbiota eats all nutrients so pathogens starve

• niche exclusion: microbes take up space on the epithelial cell layer to prevent pathogen attachment

• antimicrobial production: secrete acids that ibhibit or kill competitors

• immune priming: stimulate natural killer cells and B lymphocytes that are ready for threats

one health and bacteria

• control animal spread = control human emergence due to interconnectedness of both

primary pathogen

• causes disease in a host regardless of the hosts resident microbiota or immune system

opportunistic pathogen

• causes disease only in the absence of normal host resistance

• target when the hosts immune system is weak

host pathogen specific interactions

• type 4 pili

• P-fimbriae

• lnlA

• lnlB

quorum sensing

As more bacteria are present, more of these signals build up.

bacteria communicating with chemicals to decide when there are enough of them to act as a team.

virulence factors

1. Enter (get into the host)

• Adhesins (help bacteria stick to cells)

• Pili / fimbriae

2. Spread (move through tissues)

• Enzymes like hyaluronidase, collagenase

3. Hide (avoid the immune system)

• Capsules (hide from phagocytes)

• Antigenic variation

• Biofilms

4. Damage (actually cause disease)

• Toxins (exotoxins, endotoxins)

• Enzymes that destroy cells

how SpA (Protein A) helps Staphylococcus aureus evade the immune system

• SpA binds the Fc region of antibodies (IgG)

• This flips the antibody around the wrong way

• Hide (avoid being eaten)

  • Because antibodies are attached incorrectly, immune cells can’t grab onto the bacteria

  👉 Result: Less phagocytosis

• SpA can bind to B cell receptors (VH3 region)

• This causes abnormal activation or death of B cell

apoptosis vs phagocytosis

Apoptosis is programmed cell death (suicide) where cells break into membrane-bound bodies, while phagocytosis is the process where immune cells consume and digest these dead cells or foreign particles

nematodes

roundworm

life cycle

L1

L2

L3 * infectious stage

L4

L5/ adult stage

what stages happen in the definitive final host

L3

L4

L5

hypobiosis

• state of developmental arrest

• metabolic dormancy

transmisison routes

• oral

• skin penetration

• transmammary

• transplacental

• vector borne

• pratenic host

vector borne

• mosquitoes

• essential for completion of life cycle

paratenic host

• not essential for completion of life cycle

direct

outside the host

indirect

parasitize intermediate vector host

common larval migration patterns

• Mucosal - larvae - gut (mucosa) 

• Tracheal - gut/skin - lymph/ blood - lungs - gut 

• Hepato-tracheal - gut/skin - lymph blood - liver - lungs - gut 

• Somatic - gut/skin - lymph/blood - various tissues (results in larval arrest) 

Treatment:

• Anthelmintic drugs are primary. Resistance is a growing concern.

Strongylids 

• Ostertagia - common parasite for cattle 

Ascarids - three lips 

• Perforation of the gut 

  • This allows digestive contents (food, acid, bacteria, stool) to leak into the abdominal cavity, causing severe infection (peritonitis) or sepsis

• Milk spot in swine  

• Drug efficacy 

• Seasonal treatment 

• Switching action classes 

• Pasture rotation 

• Refugia - refuge of parasite that remain drug susceptible 

• Targeted selective treatment

one health perspective with parasites

• Elimination requires treating humans and animals.

• Environmental sanitation is critical.

• Zoonotic parasites jump between species.

MAMPs

microbe-associated molecular patterns (MAMPs)

inflammation

early component of healing after an injury

the 5 pillars of inflammation

1. Calor (Warmth/Fever)

2. Rubor (Redness/Erythema)

3. Tumor (Swelling/Oedema)

4. Dolor (Pain)

5. Functio laesa (Loss of function)

• Pattern Recognition Receptors (PRRs):

• Includes TLRs, RLRs, and NLRs.

• Sensors on host cells (like macrophages) that detect "invaders."

• Microbial Signals (PAMPs/MAMPs):

• LPS: Found in Gram-negative bacteria.

• Peptidoglycans: Found in Gram-positive bacteria.

• SCFA (Short Chain Fatty Acids): Commensal metabolites that can inhibit neutrophil activation to maintain balance.

cytokines

• Pro-inflammatory cytokines: IL-1, IL-6, IL-8, and TNF.

Sequential Steps of inflammation

• Release: Histamine and prostaglandins are released.

• Dilation: Capillaries dilate and clotting begins.

• Recruitment: Chemotactic factors attract phagocytic cells.

• Consumption: Phagocytes (neutrophils, macrophages) consume pathogens and debris.

• Phagocytes

neutrophils and macrophages

phagocytosis

a process used by certain cells in the body to engulf and digest large particles, such as bacteria, dead cells, or debris.

Cells that perform phagocytosis

• Macrophages

• Neutrophils

• Dendritic cells

• NK cells (natural killing cells)

Dendritic cells

are professional antigen-presenting cells that bridge the innate and adaptive immune systems. They detect, capture, and process antigens from pathogens or damaged cells and present them to T lymphocytes, thereby initiating and modulating immune responses.

Antigen uptake, processing, and presentation via MHC molecules to T cells.

Neutrophils

a type of white blood cell and the most abundant form of granulocytes in mammalian blood. As key components of the innate immune system, they act as rapid responders to microbial infection and inflammation, eliminating pathogens through phagocytosis and enzymatic destruction.

• Acute vs. Chronic:

• Acute: Fast onset, lasts days, involves neutrophils, results in healing or abscess.

• Chronic: Delayed onset, lasts months/years, involves mononuclear cells (monocytes, lymphocytes), results in tissue destruction or fibrosis.

The Big Myth

•  It is FALSE that eliminating all microbes is the best way to heal.

• Microbial sensing is necessary to promote wound

  healing

• The 4 Phases of Healing:

• Hemostasis: Immediate clotting and vessel constriction.

• Inflammation: Innate immune activation to clear pathogens (1–6 days).

• Proliferation: Granulation tissue forms and wound edges contract.

• Remodeling: Scar tissue replaces granulation; processes are silenced.

Hemostasis:

•  Immediate clotting and vessel constriction.

Inflammation:

•  Innate immune activation to clear pathogens (1–6 days).

Proliferation:

•  Granulation tissue forms and wound edges contract.

Remodeling:

•  Scar tissue replaces granulation; processes are silenced.

Dysbiosis:

• An imbalance (like an overabundance of S. aureus) causes persistent inflammation.

Biofilms:

• : Drug-resistant bacterial "shields" that cause wounds to stagnate in the inflammatory phase, preventing repair.

Staphylococcus

epidermidis in wound healing

Induces TLR2 signaling

via lipoteichoic acid from

cell wall

• Limits inflammation

• Accelerates transition

from inflammation

phase to proliferation

phase

§ Triggers T-cell activation

§ Drives AMP production

§ Promotes re-

epithelialization

Staphylococcus aureus impair wound healing

Overabundance = high

rates of skin infection

§ Secretes pore-forming

toxins

• Drives pro-inflammatory

responses

• Damages tissues &

increases vascular

permeability

§ Forms biofilms with anti-

phagocytic activity

Impaired wound healing

Scar tissue can accumulate

§ Persistent inflammation, delayed healing

§ Duration and amount of inflammation

§ Excessive inflammation, delays transition to proliferative phase

• Infiltration and proliferation of bacteria

• Necrosis

• Drug resistant biofilms

• Inability of cells to response to reparative stimuli

Acute inflammation

Intravascular coagulation

§ Capillary leakage

§ Vasoreactivity

§ Leukocyte infiltration

Chronic inflammation

Microvessel angiogenesis

§ Structural remodeling

§ Lymphocyte homing

High-Fiber Diets:

• Promote diversity and the growth of beneficial, saccharolytic (sugar-breaking) bacteria like Prevotella.

Western Diets:

• High in saturated fats and simple sugars; these typically reduce microbial diversity and favor pro-inflammatory taxa.

Short-Chain Fatty Acids (SCFAs)

 Produced when microbes ferment dietary fiber.

•  Key SCFAs include:

• Butyrate: Primary energy source for colon cells; maintains gut barrier integrity.

• Propionate & Acetate: Regulate appetite and improve insulin sensitivity.

Butyrate:

•  Primary energy source for colon cells; maintains gut barrier integrity.

Propionate & Acetate:

• Regulate appetite and improve insulin sensitivity.

Secondary Bile Acids:

Microbes transform primary bile acids (from the liver), which then signal through host receptors to regulate glucose and lipid metabolism.

Germ-Free (GF) Models:

• Animals raised without any microbes are generally leaner and resistant to diet-induced obesity compared to "conventional" animals.

• Fecal Microbiota Transplants (FMT):

• From Obese to Lean: Transferring the microbiome from an obese mouse into a lean GF mouse causes the recipient to gain fat, even on a standard diet.

• Human-to-Mouse: Transplanting microbes from obese humans into mice induces metabolic dysfunction in the animals.

• Clinical Findings: In humans, transferring "lean" donor microbiota to patients with metabolic syndrome can temporarily improve insulin sensitivity.

Barrier Disruption:

• A poor diet or loss of beneficial microbes (like Akkermansia) thins the protective mucus layer.

Metabolic Endotoxemia:

•  When the gut barrier is "leaky," Lipopolysaccharides (LPS) from bacteria enter the bloodstream.

Systemic Inflammation:

 LPS triggers pattern recognition receptors (like TLR4), leading to chronic, low-grade inflammation in the liver and adipose tissue—a root cause of insulin resistance.

Bile Acid Imbalance:

• Dysbiosis disrupts the transformation of bile acids, leading to poor activation of the FXR and TGR5 receptors, which are critical for healthy liver and fat metabolism. 

Impaired SCFA Signaling:

• Reduced fiber leads to lower SCFA levels, which means less activation of G-protein coupled receptors (GPR41/43) that normally help control glucose and energy expenditure.

Standard environment

+ Microbes

low fat diet - lean

high fat diet - obese

Germ-free environment

- Microbes

low fat or high fat diet

lean mouse

Differences in microbiota of obese mice

Obesity associates with shifts in the ratio of

Firmicutes to Bacteroidetes (F:B ratio). However, this

pattern is not universal across human populations.