Staphylococcus aureus: MRSA

S. aureus is a leading bacterial cause of serious human infections in both healthcare and community settings, and is increasingly difficult to control due to expanding resistance to multiple antibiotic classes. Methicillin-resistant S. aureus (MRSA) strains have disseminated on a global scale and are associated with poor patient outcomes, increased length of hospital stays, and significant economic costs to the healthcare system.

The Pathogen

S. aureus is a Gram-positive coccus-shaped bacterium that may colonize up to 30% of humans, often asymptomatically, but armed with several virulence mechanisms may lead to invasive disease.  These include surface proteins that allow colonization of the skin and respiratory tract and factors that interfere with clearance by phagocytes (capsule), antibodies (protein A), complement (SCIN), and oxidative burst (catalase, carotenoid pigment). S. aureus also produces membrane-damaging toxins (α-toxin, leukocidins) that disable immune cells and promote tissue spread, and factors that provoke uncontrolled immune activation (superantigens) or pathological blood clotting (coagulase).

"Staph" Infections

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Known since ancient times (e.g. the boils afflicting the Biblical figure  Job), we continue to witness an increasingly high incidence of serious S. aureus skin and soft tissue infections, pneumonia and bacteremia, occurring both in healthcare and community settings. Though no patient group is excluded, serious S. aureus infections disproportionately affect vulnerable populations including the elderly, juveniles, cancer patients, diabetics (and those in intensive care units, where metastatic diseases such as endocarditis, deep organ abscess, and sepsis can develop. MRSA bacteremia causes a significant disease burden and high case fatality (20% to 30%), double that seen with methicillin-susceptible S. aureus strains.

MRSA Antibiotic Resistance

S. aureus antibiotic resistance mechanisms include enzymatic inactivation (β-lactamase), decreased affinity to altered  drug targets (mutated penicillin-binding protein 2a in MRSA, peptidoglycan D-Ala-D-Lac in vancomycin-resistant strains), and efflux pumps (fluoroquinolones and tetracycline). MRSA has acquired complex genetic loci (e.g. mec elements or the vanA operon) through horizontal gene transfer, while resistance to other drugs, including the newer antibiotics linezolid and daptomycin, have developed through spontaneous mutations and natural selection.

 

Antimicrobial Warfare on Skin

CHARM Investigators transplant good bacteria to kill MRSA

Healthy people have many skin bacteria producing previously undiscovered antimicrobial peptides. But people with eczema have the wrong type of bacteria and are prone to MRSA infection. By isolating and cultivating the good bacteria, these could be administered to patients lacking them, immediately reducing MRSA levels.

Read the Article from Science Translational Medicine