Med. Bac. Chapter 4 - Staphylococcus

Who first described Staphylococcus as a leading cause of SSTIs?

Alexander Ogsten

What did Alexander Ogsten describe the appearance of Staphylococcus as?

The roe of fish

Who differentiated S. aureus from S. epidermidis?

Julius Rosenbach

What are the 2 species of Staphylococcus primarily responsible for most human infections?

S. aureus and S. epidermidis

(T/F) S. aureus is the major culprit of human infections (~70%) and S. epidermidis is the minor (~20%).

True

What group does Staphylococcus belong to?

Firmicutes

Describe Staphylococci.

They are gram (+), facultatively anaerobic cocci

What is the carotenoid that gives S. aureus its signature yellow/golden appearance?

Staphyloxanthin

What is the special crossbridge S. aureus has that makes its cell wall unique?

Pentaglycine (Gly5)

What are the 3 main reservoirs of S. aureus?

Animals, humans, and the environment.

S. aureus can asymptomatically colonize what 3 areas of the human body?

URT, GIT, and skin

What is the human carriage rate of S. aureus in humans?

20-30%

(T/F) S. aureus is an opportunistic pathogen.

True

What species of Staphylococcus is commonly attributed to community acquired UTI?

S. saprophyticus

What bacteriocin is an endopeptidase that targets the pentaglycine crossbridge of S. aureus?

Lysostaphin

Staphyloxanthin in S. aureus protects them from what?

ROS

The majority of S. aureus infections are what?

SSTIs

What is defined as “superficial papules that progress to flaccid bullae that rupture to form a purulent, scaled erythema”?

Impetigo

What is defined as “localized purulent SSTIs characterized by WBC and fibrin infiltration and toxin-mediated necrosis”?

Abscesses

What is an example of an abscess?

Carbuncle

What are the 4 life-threatening infections S. aureus can cause besides SSTIs?

SAB (S. aureus Bacteremia), pneumonia, osteomyelitis, endocarditis

Coagulation of S. aureus in blood can lead to what?

Vascular occlusion and infarction

(T/F) S. aureus can also asymptomatically colonize and opportunistically infect animals and cause URTI, sepsis, mastitis, and others.

True

What adherence factor is responsible for S. aureus ability to colonize the URT?

ClfB (clumping factor B)

What does ClfB bind to?

Loricrin

(T/F) Loricrin is the most abundance protein in the nasal cavity of humans and animals.

True

(T/F) Anti-ClfB antibodies reduces S. aureus URT carriage in mice.

True

Following skin entry, what 4 barriers does S. aureus encounter?

SALT (Skin associated lymphoid tissue), AMPs (antimicrobial peptides), complement, and antibodies

AMPs can bind to bacterial membranes and cause what 2 types of cytotoxic pores?

Barrel-stave and toroidal

What 3 virulence factors protect S. aureus from immune peptides?

Aur (aureolysin), Sak (Staphylokinase), and MprF (multiple peptide resistance factor)

What is aureolysin?

A metalloprotease that cleaves immune peptides

What is staphylokinase?

A kinase that inactivates immune peptides via phosphorylation

What is MprF?

A lysine transferase that lysinylates membrane phospholipids, giving it a net (+) charge to repel cationic AMPs

What osmoprotectants does S. aureus use to retain water (when on the skin)?

Glycine-betaine and proline

What special adherence factor does S. aureus use to bind to corneocytes on the skin?

Serine-aspartate repeat protein D (SdrD)

What does SdrD bind to?

Desmoglein-1

(T/F) S. aureus forms coagulative clots in tissue via agglutination of cells that protect them from the immune system.

True

What 2 VFs does S. aureus use to form coagulates?

Coa (coagulase) and ClfA (clumping factor A)

What does Coa (coagulase) do?

Activates host thrombin and promotes conversion of fibrinogen to fibrin

What does ClfA do?

Binds to host fibrin to form clots

What is alpha hemolysin (Hla)?

A pore forming toxin (PFT) that forms homoheptameric beta-barrel pores in host membranes

(T/F) Secreted Hla (alpha-hemolysin) punches holes in host tissues and causes chemiosmotic failure, barrier defects, and dermonecrosis.

True

(T/F) Infiltration of immune cells to S. aureus coagulates and fibrin deposition leads to containment (i.e. abscess) and liquefactive necrosis.

True

What toxin cleaves desmoglein-1 in corneocytes and causes bullous impetigo?

Exfoliative toxin A (ETA)

In addition to their original roles, Aur and Sak can also inactivate what 2 immune proteins?

IgG and complement C3b

Untreated SAB (S. aureus Bacteremia) can lead to what?

Septic shock

What are 2 components of S. aureus surface that can act as endotoxins?

Teichoic acids and lipoteichoic acids (LTA)

What toxin is primarily responsible for causing septic shock?

Toxic shock syndrome toxin (TSST-1)

What are some presumptive symptoms for S. aureus SSTIs?

Erythema (rash), swelling with suppuration, afebrile

What are some presumptive symptoms for SAB?

Abnormal vitals, febrile (fever), hypotension, tachycardia, tachypnea

What is an example of an NAAT (Nucleic acid amplification test)?

Xpert MRSA/SA

Xpert MRSA/SA primarily screen for what from blood and exudate samples?

mecA

What are 2 direct examination tests used for definitive diagnosis of a Staphylococcal infection?

Coagulase and Mannitol Salt Agar (MSA)

(T/F) The coagulase test tests for the presence of the coagulase enzyme, with a positive test showing a visible formation of a clot.

True

Which of the 2 Staphylococcal pathogens are coagulase (+)?

S. aureus

Which Staphylococcal pathogen is coagulase (-)?

S. epidermidis

(T/F) Mannitol salt agar (MSA) is a selective differential media, with a high NaCl concentration selecting against gram (-) and for gram (+), and mannitol, of whose fermentation turns the media yellow from pH depression.

True

(T/F) S. aureus can ferment mannitol and turn the agar yellow, while S. epidermidis cannot ferment mannitol.

True

What was the example of a prevention strategy against infection via decolonization?

Mupirocin topical

(T/F) There are currently no licensed vaccines against S. aureus.

True

What is the name of the Pfizer S. aureus vaccine currently in trials?

SA4Ag (S. aureus 4 antigen)

(T/F) There is 0% efficacy in preventing postoperative or surgical site SSTIs.

True

S. aureus is resistant to beta-lactams due to what?

Beta-lactamases

What was the synthetic penicillin derivative meant to be beta-lactamase resistant?

Methicillin

What do methicillin and beta-lactams bind to?

PBP (penicillin binding protein)

MRSA encodes what that gives them resistance to methicillin?

PBP2a that has low binding affinity

What gene encodes for PBP2a?

mecA

Where is mecA located?

Staphylococcal cassette chromosome mec (SCCmec)

(T/F) SCCmec can participate in HGE (horizontal gene exchange) via transformation, transduction, and conjugation.

True

(T/F) MRSA are less fit than MSSA.

True

What are the first-line antibiotics for MSSA?

Beta-lactamase resistant cephalosporins → Cefazolin and Nafcillin

What are first-line antibiotics for MRSA?

Vancomycin, clindamycin, linezolid, gentamicin