Micro

3/5/25:

Impact of Gut microbiota:

Balance of t regulatory cells. 

Germ free mice: when mice that are born via c-section in a totally sterile environment, and on occasion treat the mother with antibacterial. This allows you to regulate what the mouse is colonized with, so you can study specific bacteria/bacterial families of interest.

Knock-out mice and knock-in mice are two types of mice that we manipulate the genes of. 

Impact of gut microbiota: early life

Microbiome is different between c-section infants and standard birth, vaginal birth infants have microbiomes closer related to the mother. Breastfed infants have more commensal bacteria, as breast milk has oligosaccharides that promote their colonization. 

Changes in the microbiome occur whenever the infant puts anything in their mouth, or any first infections. As the infant develops and the diet changes so does the microbiome, as well as the person develops you are introduced to different colonization events. 

Link between the gut microbiota and immune system has long been studied, and it has been found to be important for adaptive immune response. 

IBD- which has evidence that it may be transmitted to family members. 

Impact of microorganisms: obesity and nervous

Obesity:

• Normal mice have 40 percent more fat than germ-free mice with the same diet

• When germ-free mice were given normal mouse microbiota, they started gaining weight.

• Mice that are genetically obese have different microbiota than normal mice

• Obese mice have more firmicutes compared to bacteroides

Skin microbiota: 1 million resident bacteria per square centimeter of skin

3/7/25(23.4-6):

*Exam wednesday

Symbiotic relationships, prebiotics, probiotics, consortia, 

*Infection does not equal disease, it simply means the bacteria colonizes the organism. 

3/10/25(23.7-10; 23.14-16):

3/12/25:

Lignin- non-digestible components of plants

Quorum sensing- bacteria will produce autoinducers that act either on the same bacteria or neighboring bacteria, to give an idea on bacteria density. Once the bacteria reach a high enough level of density they perform a function, such as bioluminescence in Hawaiian Bobtail Squid.

This squid symbiotic relationship is one of the first that we understood.

Foregut fermentation: fermentation chamber precede the small intestine

Hindgut fermentation: 

Rumen composition becoming more acidic makes the blood acidic as well, which potentially lethal for the cow

Chapter 25: Microbial Infection and Pathogenesis 

There are very few microorganisms that cause disease. Those that do though possess specific traits that underlie their pathogenic lifestyles.

• Express molecules that promote pathogenicity (virulence factors)

• Things that promote interaction with specific cells, disrupt normal cellular function, circumvent the host's immune responses. 

Pathogens: microbial parasites (specifically parasitic interactions) that cause disease or tissue damage.

• Primary pathogens cause disease by direct interaction with healthy host

• Opportunistic pathogens are pathogens that only cause disease when it has gained access to other tissue sites or host is immunocompromised. 

• Pathogenicity: the ability of a parasite to inflict damage on the host

Infection:

1. Release of toxins that damage host

2. Outcompete host for nutrients

   1. Outgrow host

   2. Lyse cells or tissues

Virulence: the ability of the pathogen to induce disease

Virulence Factors: Factors that allow for infection and disease

Any structural or soluble product that increase pathogenicity:

• Things that aid in attachment

• Things that aid in invasion

• Things that allow for toxicity

  • Exotoxins that are secreted

  • Endotoxins (LPS)

 Evade Immune Response

These control the degree to which the pathogen causes damage, invasion, infectivity.

3/14/25:

Operon- controls for virulence 

G-C ratio is commonly used for identification

Pathogenicity islands

Protein secretion systems:

Types I, III, IV, and VI

Measuring Virulence:

Infectious dose 50, the dose needed to infect 50% of the mice

Lethal dose 50, the dose needed to kill 50% of the mice 

Attenuation: is the decrease or loss of virulence. Attenuated strains are useful for studies to understand pathogenicity and identify virulence factors. 

Infection process:

1. Adhesion

   1. Adhesins are the main term used for molecules that bind to a specific receptor on a host

2. Invasion

   1. Invasins, surface molecules that allow for penetration of cell or tissue

3. Colonization can be option 4 or 5

   1. Multiplication of bacteria in host

4. Mutualistic

5. Parasitic 

3/17/25:

Adhesins- is a term used for any molecules that are associated with attachment/adherence

Invasion during an infection can have two meanings:

Invasion onto epithelial layers such as your skin or in a mucosal membrane to gain access to nutrients to allow for infection. Typically uses invasins.

The other is this: further invasion of that tissue or invasion from one tissue type to another. This is also called invasiveness

Colonization- the growth of microorganisms after they’ve gained access to host tissues. Since each body region differ chemically and physically from others, a selective environment for the growth of certain microbes occurs. 

Colonization typically starts with mucous membranes.

Lipid membranes- called hemolysins usually, due to the testing involving blood cells. 

The Disease Process: Following invasion and colonization of tissue/cells, some pathogens may release additional virulence factors.

Virulence factors that can be added:

Enzymatic virulence factors (invasins): UFs, affect macromolecules, biomolecules, are hemolysins, ECM, and blood clotting.

Exotoxin production (secreted toxins):

• AB Type Exotoxins- can mess with cells that control muscle stiffness

• Cytolytic Exotoxins- 

• Superantigen Exotoxins- tricks the immune system into creating a massive immune response

Endotoxins:

• Part of a cell

• Lipid A of LPS

• TLR4

• Can cause effects similar to superantigen. Specifically systemic inflammation. 

Evasion of the Immune Response

Invasiveness:

• Invasiveness requires a pathogen break down host tissues.

  • This is often done with pathogen-secreted tissue destroying enzymes that attack host cells.

• The Extracellular Matrix is targeted

  • Hyaluronidase breaks down hyaluronic acid which is an important part of the extracellular matrix.

• Blood clots are targeted as well, either causing or preventing blood clotting. 

IgA protease: IgA is the major antibody that protects mucosal surfaces by binding to pathogen surfaces. Protease is produced by pathogens to lyse IgA

Toxigenicity: the ability of a pathogen to release toxins. 

Exotoxins: soluble, heat-labile, proteins

• Secreted into surroundings as pathogen grows

  • Exotoxins often travel from site of infection to other tissues or cells where they exert their effects

  • Can be classified based on their targeted tissues

• Among the most lethal substances known

• Are highly immunogenic

Cytolytic (membrane-disrupting) exotoxins:

• Work by degrading cytoplasmic membrane integrity, causing cell lysis and death.

• pore -forming toxins that poke holes into the cell membrane

Superantigens:

• Leads to overactivation of the adaptive immune cells, T cells

• Causes the T cells to overexpress and release a large amount of inflammatory mediators called cytokines.

• This leads to massive widespread inflammation

• Toxic shock syndrome

  • Hypotension, intestinal disruption, organ failure and systemic shock

  • Giving time for the microbe to disseminate

Microbiome: a functional collection of different microbes in a particular environmental system

What is true about different human microbiome sites? They are diverse in families of bacteria present and similar in major metabolic pathways expressed.

Most of the gut microbiome is present in the colon and contains mostly anaerobic bacteria

When does initial colonization of the microbiome happen? At birth.

Which of the following is true about skin microbiota? Bacteria that break down fats to use for energy are found in sebaceous areas of the skin such as Propionibacterium. 

Which of the following is true about herbivore animals? Microbes break down cellulose, hemicellulose and lignin into glucose which are then fermented into VFAs by microbes.

Pathogenicity: the ability of an organism to cause harm to its host

Virulence: the degree to which that harm is to the host

Different strains of E. coli are able to induce different types of disease. What major components of the bacteria allow for this? Virulence Factors

Secretion Systems: proteins that can inject toxins into host cell

Pathogenicity Islands: segments of DNA that contain virulence factors

Colonization is the step of infection that involves the bacteria multiplying, thus establishing an infection.