M1 S4: Overcoming Host Immune Response

In this section you reviewed: • How the production of a biofilm is a mechanism organisms use to overcome host immune responses. Biofilms are composed of EPS and the complex bacterial community is capable of communicating with one another through quorum sensing. • How capsules, thick polysaccharide layers that reside on the outside of cells, provide bacteria with protection against the host immune system. • How bacterial toxins (both endotoxins and exotoxins) function to arrest cellular functions. • How metabolic dormancy and the ability of wild-type S. aureus to phenotype switch into SCV can aid in the evasion the immune system.

In this section you reviewed:

• How the production of a biofilm is a mechanism organisms use to overcome host immune responses. Biofilms are composed of EPS and the complex bacterial community is capable of communicating with one another through quorum sensing.

• How capsules, thick polysaccharide layers that reside on the outside of cells, provide bacteria with protection against the host immune system.

• How bacterial toxins (both endotoxins and exotoxins) function to arrest cellular functions.

• How metabolic dormancy and the ability of wild-type S. aureus to phenotype switch into SCV can aid in the evasion the immune system.

In this section you reviewed:

• How the production of a biofilm is a mechanism organisms use to overcome host immune responses. Biofilms are composed of EPS and the complex bacterial community is capable of communicating with one another through quorum sensing.

• How capsules, thick polysaccharide layers that reside on the outside of cells, provide bacteria with protection against the host immune system.

• How bacterial toxins (both endotoxins and exotoxins) function to arrest cellular functions.

• How metabolic dormancy and the ability of wild-type S. aureus to phenotype switch into SCV can aid in the evasion the immune system.

Infection caused by 4 stages: what are they

1. Entry 

2. Invasion and colonization of tissue 

3. Evasion of the host immune response 

4. Infection

what is infection

• vercoming of immune system caused usually by virulence factors 

  • Molecules that are made by microo that increase their effectiveness and able them to infiltrate host 

what are the 4 ways to evade immune system

1. Biofilm production

2. Capsules a way of avoiding phagocytosis 

3. Toxin production 

4. Metabolic Dormancy 

why are biofiolms made?

• Mechanism to overcome immune system and helps to stop penetration of antibiotics and other cellular function 

what makes up a biofilm?

• Made of different adhesive cells embedded in an extracellular matrix and extracellular polymeric substance 

what are Extracellular polymeric substances (EPS)

• Extracellular polymeric substances (EPS): EPS are natural polymers of high molecular weight secreted by microorganisms into their environment. EPSs are important for the structural integrity of biofilms and help determine the physiochemical properties of a biofilm.

where are biofilms found

Commonly found on prosthetic joints (knee and hip replacement = prosthetic joint infections (PJI)), tooth brushes, stainless steel, sink 

T or F: biofilms are made of the same type of bacteria

F: Diverse and dynamic community 

• Mixed bacterial population 

what is quorum sensing? why do bacteria do it?

• Quorum sensing: The regulation of gene expression in response to fluctuations in cell-population density. Bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. Bacteria within the biofilm talk to each other to see when they need to move around.

T or F : Antimicrobial can not penetrate biofilms

T; = more difficult to treat 

• Why do they use quorum sensing? Why communicate? 

Quorum sensing is the bacteria's mode of communication that allows them to convey information to other bacteria in the biofilm. Bacteria require constant communication to modulate the stages of the biofilm life-cycle. Bacteria communicate with each other to indicate the presence of nutrients or lack of nutrients in a particular location. If there are plenty nutrients than the biofilm will remain in that area to mature and if there is a lack of nutrients,

dispersal cells will be formed so the biofilm can relocate.

what happens if a biofilms breaks off

• Represents a nidus of infection that can break off and be the source of infections at others sites 

Steps of making a biofilm

1. Adhesion: the bacteria adheres to a new surface

2. Accumulation: other bacteria begins to accumulate on the already present bacteria

3. Maturation: the biofilm matures

4. Dispersion: when the biofilm requires more nutrients, bacteria will break off and re-locate

what is a Capsule

• Capsule = a thick polysaccharide layer that resides outside of the cell 

a Capsule is an example of what

• Capsule production = virulence factor 

T or F: Can see if capsule or not with capsule stain (fuzzy grey border = capsule ) 

T

How do capsulated bacteria interact with macrophages 

• Capsulated bacteria 

  • Antiphagocytic shield: The outer capsule—usually made of thick polysaccharides or hyaluronic acid—hides the inner cell wall and masks vital targets from macrophage receptors. [1, 2]

  • Blocked opsonization: The slippery, often negatively charged or hyperviscous capsule prevents complement proteins and antibodies from working effectively, stopping opsonophagocytosis. [1, 2]

  • Immune evasion: Because macrophages cannot easily grab or swallow them, encapsulated bacteria survive longer in the host and cause severe disease. [1, 2, 3]

what are toxins made by bacteria and what is the target?

• Toxins = small proteins or polysaccharides that are able to arrest cellular function or lyse host cells 

• Targets = plasma membrane or cytoskeleton

2 types of bacterial toxins

endotoxins and exotoxins

What are endotoxins?

Endotoxins are toxins that are not secreted, but are liberated when the bacteria lyse.

what is Lipopolysaccharide (LPS)?

LPS is a structural component within the outer membrane of Gram-negative bacteria. It is composed of the inner core, outer core, O antigen and Lipid A component.

The Lipid A component of LPS is a heat stable endotoxin that is a potent stimulant of the immune system even at small concentrations.

T or F you need a high concentration of Lipid A compinment of LPS to stimulant of the immune system

F: The Lipid A component of LPS is a heat stable endotoxin that is a potent stimulant of the immune system even at small concentrations.

Lipid A, when present in high concentrations in the body, may cause septic shock and death via an excessive immune response.

what is an exotoxin? what type of bacteria are they found with?

Exotoxins are defined as toxins secreted by bacterial cells. They are most commonly produced inside pathogenic Gram-positive bacteria.

T or F lipid A component is mainly found in gram positive bacteria

F: LPS is a structural component within the outer membrane of Gram-negative bacteria. It is composed of the inner core, outer core, O antigen and Lipid A component.

who (±) mainly makes exotoxins

gram postive

An example of a bacterial exotoxin is the macrophage cytotoxin produced by Salmonella spp. how does this work?

This bacterium can gain entry into host macrophages and produce toxins that impair the membrane ruffling and macropinocytic * activities of infected macrophages which can lead to cell death. These processes are essential for the macrophages to perform phagocytosis.

The macrophage cytotoxin produced by Salmonella spp. can ultimately lead to this bacteria evading the immune system through reducing the number and function of key innate immune cells.

Salmonella spp mainfests clinically as

Clinically, this bacterial infection manifests as food poisoning with the symptoms such as nausea, vomiting, and diarrhea however, these symptoms are related to an enterotoxin produced by the bacteria rather than the cytotoxic effects.

• Enterotoxin (exotoxin) = effects gut 

what are the 3 types of exotoxins?

Enterotoxins

neurotoxins

cytotoxins

what do Enterotoxins do

• Enterotoxin = effects gut 

• Neurotoxin do what

• Neurotoxin = effects nervous tissue 

cytotoxins do what

• Cytotoxin Toxic to cells. Cytotoxins damage, injure, or kill living cells. [1, 2, 3]

what does Metabolically quiescent mean

• Some bacteria enter dormant state (metabolic activity and growth is stopped or slowed down)

how does Metabolic Dormancy evade the immune system

• Impacts antibiotics to target cell (usually only target metabolically active) and reduced virlence goes unnoticed

give an example of a bacteria that uses Metabolic Dormancy to evade immune system

S. aureus

There are four main mechanisms through which bacteria evade the host immune system. Bacteria can use one or a combination of these defences. what are they and quickly explain them

•  A biofilm is formed when any group of microorganisms stick together to form a layer. Biofilms are impenetrable by antimicrobials and are therefore hard to treat. When a biofilm forms on a prosthetic joint, the only solution is to remove and replace the joint.

• Capsules are a thick polysaccharide layer on the outside of a bacterium. It provides an extra layer of tough protection for the cell.

• Bacterial toxins have the ability to damage or even kill host cells, removing their ability to eliminate the foreign invader.

• Finally, some bacteria enter of state of metabolic dormancy, where the growth and activity is stopped or slowed, so these cells cannot be recognized by the host immune system.