Pathogens a/b - Skinfections + UTI Flashcards
What is the main structural component of bacteria cell walls?
-Peptidoglycan
> N-acetylmuramic acid (NAM), + N-acetylglucosamine (NAG) crossed linked by penicillin-binding proteins (vary for different bacteria)
Identify the differences between Gram-positive and Gram-negative cells, specifically focussing on the cell wall.
-thicker wall
Name and describe the major pathogenic genera and species of Gram-positive bacteria.
What are the processes that results in infection?
What is the organism that is likely to be causing the soft-tissue infection?
-Staphylococcus aureus, so always have that in mind. It is on our own skin. Bites and water-based injuries are examples where other organisms might be present instead though!
Why can GAS and staphylococci cause soft-tissue infections? ADHESIONS
- Adhesins > Bind to damaged epithelial cells (release fibronectin and other matrix proteins - when injured)
- Bacteria have receptors on their surfaces that allow binding to these.
> Staphylococci use MSCRAMM to bind multiple different matrix proteins on damaged cell
> GAS use F-protein to bind fibronectin directly.
…Prevents expulsion of blood = Colonisation at wound
How does immune system deal with colonisation?
- Bacteria begin to replicate, which brings them into contact with TLRs on, and in, keratinocytes
- Keratinocytes detect lipoteichoic acid (LTA), and then secrete ß-defensins to damage the bacteria
- Macrophages also detect LTA, which results in the secretion of pro-inflammatory cytokines and the initiation of the inflammatory process
- Cytokine productions drive NO production, and recruitment of localised complement proteins; prolonged cytokine production results in neutrophil recruitment
- C3 accumulates on bacteria and alternative complementary pathways are activated, forming C3b
- C3b is recognised by phagocytic complement receptors on macrophages, and the bacteria is phagocytosed
How do the VIRULENCE factors of GAS and S. aureus result in them dodging the immune system
- GAS: Avoid getting covered in complement :
M-protein > Binds to factor H > Pulls out of serum and uses it to block conversion of C3 > No C3b > No opsonisation > No phagocytosis - BOTH : Produce polysaccharide capsules > block immune cell receptors from binding to and recognising the cell
- S. aureus : Uses Coagulase > Coat in host-derived fibrin, blocking immune recognition to a large extent > high levels form hard inclusions in the tissue which can stick around for a long time.
What is special about streptokinase?
-Invasin
> produced by many strains of GAS – digest the clots (bodies way of stopping bacteria escape) and allow escape into the circulation.
-Anti clotting therapy for infarctions
What does the bacteria produce that allows it to spread further into tissue?
What do they produce that digests the extracellular matrix to allow deeper invasion?
What do neutrophils do when infection spreads? How do bacteria overcome this? INVADE
- Invasins
- Hyaluronidase
- deploy their DNA to form neutrophil extracellular traps (NETs).
- produce DNAses to literally eat their way out and continue the infection.
What does S.aureus produce in order to counter an adaptive immune response via antibodies? How would we need to counter this?
-Protein A that is capable of binding to the Fc portion of the antibodies, and flipping them around
> Toxin activity is not blocked
> Shields bacteria from immune system
-To produce antibodies for Protein A itself
How direct killing of immune cells facilitates continuation of infections?
What toxins are released by:
-streptococci
-beta-haemolytic streptococci (GAS and GBS)
-S. aureus
- haemolysin to break down RBCs for iron
- Two haemolysins (SLS and SLO), which cause major damage in ischaemic conditions GAS=fasciitis
- Panton-valentin leucocidin (PVL) positive > Haemolysin that kills RBCs and immune cells very efficiently
What do super antigens do?
- Cause Dendrites to bind to T-helper cells without need.
-Cause massive amounts of random inflammation which isn’t targeted at the pathogen, but ensures immune system remains occupied
Summarise Pathogens 1.
ADHESINS allow persistence on/in a tissue
INVASINS allow evasion of immune recognition and spread within a tissue
TOXINS damage tissues and host cells
What are the different skin infections?
How are urinary infections classified?
-Upper urinary tract i.e renal vs Lower urinary tract i.e bladder and urethra
- Complicated : Healthcare setting/structural abnormalities/male/systemic infections- more likely to spread into upper renal infections and or caused by unexpected organism vs Uncomplicated : community
What is the most common cause of any UTI? Why?
-Uropathogenic Escherichia Coli 70-90%
- adhesins* allowing them to bind to the transitional epithelium of the urinary tract
OR HCA - Catheter
What happens during uncomplicated urinary tract infections? What are some symptoms?
What primary defences do we have?
-patient’s own GI flora colonising the tip of the urethra
-organism binds to the uroepithelium and ascends the urethra and gains entry to the bladder.
-Initially mild> immune system recognises bacteria inflammation begins> “fullness” :bladder wall begins to swell, difficulty in passing urine (as the opening of the bladder swells), change in colour and odour (bacteria and immune products are washed down the tract – known as pyuria) and if it progresses enough can result in blood loss as the epithelium is invaded into the lamina propria.
-continued high-pressure flow of urine down the urethra, dislodging the organisms. (stay hydrated)
What is the most likely reason for a complicated UTI manifesting?
-organism in the lower tract has been able to form a biofilm and remain in the bladder long after it should have been cleared > A urinary catheter makes this much, much more likely as it causes damage to the epithelium itself.
-This releases molecules that bacterial adhesins can bind to
This is why Staphylococcus aureus never cases uncomplicated, community-acquired UTIs! There are no molecules for its adhesins to bind to! If, however, a catheter is inserted, matrix proteins are released from the damaged uroepithelium cells and S. aureus can bind to them… This is why it is associated with HCA UTIs!
What is commonly used in communal settings to test for UTI?
-urinary dipstick
-midstream urine sample. Ideally early in the morning and best with the first “pee” of the day
Female <65 year old tree diagram.
When would samples and further investigations be necessary?
-Patient presenting with renal symptoms
-Male patients with urinary symptoms
-Pregnant patient (symptoms or otherwise)
-Children with suspected infection symptoms
-Other important things to look out for when suspecting UTI
What do we look for in microbiology ?
- Casts are proteinaceous deposits that form when high concentrations of protein are found in the renal tubules. These are a marker of dysfunction and are often washed down the ureters into the bladder.
-Damaged red blood cells can also become casts of themselves as their contents are scavenged by the bacteria.
Intact red blood cells are always a worry in urinary samples.
>USE CELL COUNTER SYSTEMS
What overcomes the limitations of automated counter systems?
-they cannot tell you what the organism is nor what antibiotics will affect it.
-use the cell counter to decide if culture is needed, report the findings back to the clinician and then spend 24-72hrs culturing and performing susceptibility testing
