Staphylococcus Flashcards
Staphylococcus
Gram positive bacteria.
Forms boils in skin, that combine to form arbuscules that can form carbuncles.
They can infect via lesions from injury or surgery. They can cause systemic infection.
They can cause toxic shock
Adhesins
These are cell wall associated proteins, that facilitate binding to extra cellular structures in hosts.
Fibronectin binding protein
Fibronectin is found within the plasma of the host.
FnBPA. Binds to fibronectin, causing conformational change that exposes integrin binding sites. Integrin on human epithelial cells binds the bacteria bound fibronectin. When blood is flowing out from a lesion, the bacteria is able to stick to epithelial cells to stay in the blood.
Fibrinogen
Fibrinogen is cleaved to form fibrin, which allows for clotting. Prothrombin is converted to Thrombin which cleaves Fibrinogen
Coagulase and extracellular fibrinogen binding protein (Efb)
Coagulase (Coa)
Coagulase N-terminus binds prothrombin, forming staphylothrombin. Staphylothrombin cleaves Fibrinogen, forming Fibrin and encouraging clotting. C-terminal binds fibrinogen. These clotts help protect against immune cells.
Extracellular Fibrinogen binding protein (Efb)
This protein binds fibrinogen, allowing the bacteria to bind in the clott.
This clott is able bind immune cells, bacteria and other cells.
The clott can be broken down by the Fibrolysin. This allows the bacteria to move elsewhere once there are too many bacteria in the clott for there to be enough nutrients.
ProteinA
Protein A binds Antibodies the wrong way around, binding the domain recognised by the B cell, the Fc domain. Secreted protein A can bind the B cell receptors and cause apoptosis. It is able to penetrate through the clott and spread to prevent antibodies from reaching the clott.
Superantigens
Super antigens overstimulate the immune system, causing damage to the host.
TSST1 = Toxic shock syndrome toxin1
It binds the MHCII receptor on T cells without being presented by B cells, binding outside the groove. It stabilizes the interaction between MHCII and the antigen presenting B cell, causing overstimulation of the T cell. This overstimulation can lead to vasodilation, with the vasculature becoming more permeable. This causes a large drop in blood pressure, causing respiratory problems.
Menstrual Shock from TSST2 Staph
There were supersoaker tampons that would carry staphylococcus aureus. From here the bacteria could produce TSST2 which overstimulates immunity, causing shock.
Porin forming toxins
These are Bi-component leukocidins. The individual proteins combine to form pores in the membrane of target cells. This causes apoptosis/necrosis of the cell as it starts leaking. The most prominent are PVL and gamma-haemolysin.
PVL binds to immune cells, killing them.
Gamma-haemolysin targets red blood cells, allowing for the bacteria to access iron.
Regulation of virulence factors
Different stages of growth have different levels of expression.
When first starting exponential growth, colonisation genes are expressed producing FnBPs, Coagulase, adhesins, ProteinA.
During late exponential surface protein expression falls.
During stationary phase, Staph produces more genes related to combating immunity and nutrient acquisition such as TSST1, gamma-haemolysin, PVL, toxins, etc.
During late stationary phase, Staph produces enzymes such as fibrolysins and DNAses that degrade the clott, allowing the bacteria to escape and move elsewhere.
Staph Quorum Sensing system
AgrD processed (cleaved) and released by AgrB, forming AIP. AIP is released and binds to the AgrC receptor. AgrC phosphorylates AgrA, activating AgrA. AgrA acts as a TF, promoting virulence and nutrient acquisition (gamma-haemolysin, toxins, TSST1, leukocidins) and downregulates genes related to colonisation (ProteinA, FnBPs, Cna, adhesins). AgrA is able to amplify its own signal by binding RNAII which encodes AgrA, AgrB, and AgrD.
At a low density AIP has a low chance of being received by the AgrC receptor. Once the bacteria proliferates a lot in a clott, the
The Agr operon can be a therapeutic target. Mutated Agr operons make bacteria a virulent. The peptide from another Agr group can interfere with another groups system.
Infection control
Using hand sanitisers, gloves, screening people, cleaning wounds. Understanding the infection cycle.
Vaccines
There are multiple redundant VFs, meaning that they may not be carried by all strains. There are certain key molecules needed in all Staph, making them good vaccine targets.
Multivalent vaccines can cover a range of types of Streptococcus pneumonae.
Beta-lactam antibiotics
At first, beta-lactams were the most effective antibiotic, binding to PBP2 and inhibiting transpeptidase cross-linking. Then beta-lactam resistant Staph formed, that produce Beta-lactamase which cleaves the beta-lactam ring.
The beta-lactam side chains can be modified, allowing for added functions. Such as stomach acid resistance, permeability and some prevent degradation.
Methicilin/Flucloxacillin
These two beta-lactam antibiotics have been modified to be beta-lactamase resistant. They have modified side chains that prevent beta-lactamase access to the ring.
MRSA (methicilin resistant Staphylococcus aureus)
Shortly after the introduction of Methicilin, MRSA developed. This is done via the SSCmec cassette which carries genes for producing PBP2A in response to beta-lactam. PBP2A is an alternative enzyme that is less effective than PBP2, hence why it is only expressed when PBP2 is inhibited.
Initially the cassette was only in weaker strains, but eventually it found its way into stronger strains such as EMRSA-15
