Germs We Cannot Always Kill: Methicillin-resistant Staphylococcus aureus

In this lecture, Dr. Henry Chambers provides a comprehensive overview of Staphylococcus aureus and the challenge of methicillin-resistant Staphylococcus aureus (MRSA). He begins by tracing the evolutionary history of staphylococci, emphasizing their long co-evolution with warm-blooded animals and humans. He explains the natural carriage of S. aureus in humans, noting that about 90 million people in the US are colonized, with 5 million carrying MRSA. The talk covers the host defenses against staphylococcal infection, including intact skin, antimicrobial peptides, and neutrophils, and how the bacteria counter these defenses through various virulence factors. Chambers then describes the four primary diseases caused by S. aureus: local infections, food poisoning, invasive disease, and toxin-mediated syndromes, illustrating each with clinical images. He provides estimates of disease burden, with 1-3 million skin and soft tissue infections and 150,000 invasive cases annually, half of which are MRSA. The core of the lecture focuses on the mechanisms of antibiotic resistance, particularly the role of horizontal gene transfer and mobile genetic elements. He explains that methicillin resistance is due to the mecA gene carried on a staphylococcal chromosomal cassette (SCCmec), which alters the drug target rather than destroying the drug. He traces the evolution of SCCmec elements from the original type I to more efficient types, highlighting the importance of genetic elements over strains in the spread of resistance. The talk concludes by emphasizing that antibiotic resistance is a consequence of selection pressure and that controlling genetic elements is more challenging than controlling strains.