Staph and Resistance AWM REF 2025 Flashcards
What is the main leukocidin produced by Staph. pseudintermedius?
What cytotoxins are analogous in Staph. aureus?
LUK-1 - Staph. pseudintermedius
Panton-Valentine leukocidin (PVL) and LUK-ED - Staph. aureus
What type of toxin is LUK-1 in Staph. pseudintermedius? What are the target cells? How and through what receptor does it exert its effects on those target cells?
LUK-1 is a pore forming toxin. It causes lysis of polymorphonuclear leukocytes and macrophages through engagement of CXCR2 receptor
The detection of what enzyme can help distinguish Staph from Strep?
Catalase (enzyme that breaks down hydrogen peroxide into water and O2)
Staph is catalase +
Strep is catalase -
What is a characteristic of Staph selective media?
High NaCl concentration…. because Staph is salty
How do β-lactam antibiotics work?
Inhibition of cell wall synthesis by targeting the activity of bacterial transpeptidases known as penicillin-binding proteins (PBPs). The beta-lactam antibiotics bind to the PBP to halt their effects.
Remember, Staph is a gram-positive + bacteria with a thick cell wall made up of cross-linked peptidoglycan. W/o functional PBPs, that peptidoglycan layer does not get made and the bacteria dies because of loss of structural integrity and lysis
What is the most common reason for methicillin resistance in Staph?
Production of an altered penicillin binding protein called PBP2a, which has reduced binding affinity for beta-lactam antibiotics, thus the wall gets built even though the abx is present
How is methicillin-resistant Staph typically induced/spread?
An altered penicililn binding protein PBP2a is encoded by genes mecA (or mecC). These genes can be introduced into the genome and transferred to other bacteria via SCCmec (Staph chromosomal cassette), which is a mobile genetic element
What do you know about mecC?
MecC was discovered in 2011 in LA-MRSA from European cows
But this gene was present in European hedgehogs BEFORE the development of abxs (thus proof that nature is also working independently of us)
This is thought to be a consequence of co-evolutionary adaptation of S. aureus in hedgehogs infected by the dermatophyte Trichophyton erinacei because Trichophyton naturally produces to Beta-lactam abxs, thus applying selective pressure
You have an equine patient with MRSA. What strain of MRSA is most likely involved?
MRSA strain USA 500
There is an outbreak of MRSA in a group of people with little prior community spread of MRSA, but there is an epidemiological connection with livestock. What strain of MRSA is of concern?
LA-MRSA ST398
New clonal strains of MRSP have now emerged (it’s 2025), but historically, which two strains of MRSP have emerged within North America and Europe, respectively?
MRSP strains
North America: MRSP ST 68
Europe: MRSP ST 71
What are the two sub-types of antibiotic resistance?
Intrinsic vs. Acquired
What is intrinsic antibiotic resistance?
A genus or species characteristic; often based on the absence or inaccesbility of the target structures in the respective bacteria
Enterococcus is an example of intrinsic antibiotic resistance to TMS. Can you explain why?
Enterococci are not dependent on a functional folate synthesis pathway because they can use exogenous (i.e. host) folates. Because TMS drugs interfere with folate synthesis, they do not work well for Enterococci
What is acquired resistance? What are the three major categories of acquired resistance?
Resistance mechanisms acquired due to mutations of cellular genes or the acquisition of novel/foreign genes
Three major categories of acquired resistance
1. Enzymatic modification or inactivation of antimicrobial drugs
2. Reduced intracellular accumulation (i.e. efflux pumps)
3. Alterations of target sites
What gene encodes for beta-lactamase, thus yielding penicillin resistance? What does beta-lactamase do?
blaZ
Beta-lactamase is an example of an enzymatic inactivation of an antimicrobial agent. In this case, the enzyme breaks the structure of the antibiotic before it can even bind to the target (e.g., PBPs) to disrupt the cell wall.
Plasmid mediated
Can be inducible or non-inducible
What genetic mutations confer resistance to tetracyclines via the production of efflux pumps?
Tet(K) and Tet (L)
What genetic mutations confers resistance to tetracyclines via ribosomal protection?
tet(M) amd tet(O)
What genetic explanation accounts for Staph sometimes retaining sensitivity to minocycline but resistance to other tetracyclines?
Presence/activation only of tet(k) encoding for efflux pumps, but absence of tet(M).
This means that the efflux pump (encoded by tetK) can reduce intracellular concentration of the drug but because the ribosome is not protected (b/c no tetM) if enough of the drugs gets to the target, it can work.
Minocycline is less affected by efflux pumps than other tetracyclines, but is ineffective if the ribosomal target is protected.
What is the MOA of tetracycline antibiotics?
Primary target:: 30 S ribosomal subunit
Net effect: inhibition of protein synthesis
MOA: interacts with the bacterial 30S ribosomal subunit and inhibits translation by aminoacyl-tRNA
What is the MOA of Mupirocin?
MOA: inhibits isoleucyl-transfer RNA synthase, thereby obstructing bacterial protein and RNA synthesis, ultimately resulting in cell death
What is the MOA of Mupirocin resistance, including the relevant gene?
ileS2 (formally known as mupA) encodes high-level Mupirocin resistance/tolerance via encoding an additional isoleucyl-tRNA synthase that has reduced binding affinity for Mupirocin
What is the MOA of rifampin?
Primary target: Nucleic acid (RNA) synthesis via inhibition of bacterial DNA-dependent RNA polymerase leading to, suppression of RNA synthesis and bacterial cell death
What gene encodes for rifampin resistance?
Gene rpoB encodes for a wonky beta subunit of bacterial DNA-dependent RNA polymerase
