Community-associated MRSA: what makes them special?

Abstract

While infections with methicillin-resistant Staphylococcus aureus (MRSA) were traditionally restricted to the hospital setting, novel MRSA strains emerged over the last two decades that have the capacity to infect otherwise healthy people outside of the hospital setting. These community-associated (CA-)MRSA strains combine methicillin resistance with enhanced virulence and fitness. Interestingly, CA-MRSA strains emerged globally and from different backgrounds, indicating that the "trade-off" between maintaining sufficient levels of methicillin resistance and obtaining enhanced virulence at a low fitness cost was achieved on several occasions in convergent evolution. However, frequently this process comprised similar changes. First and foremost, all CA-MRSA strains typically carry a novel type of methicillin resistance locus that appears to cause less of a fitness burden. Additionally, acquisition of specific toxin genes, most notably that encoding Panton-Valentine leukocidin (PVL), and adaptation of gene expression of genome-encoded toxins, such as alpha-toxin and phenol-soluble modulins (PSMs), further contributed to the evolution of CA-MRSA. Finally, the exceptional epidemiological success of the USA300 CA-MRSA clone in particular may have been due to yet another gene acquisition, namely that of the speG gene, which is located on the arginine catabolic mobile element (ACME) and involved in detoxifying harmful host-derived polyamines.

Keywords: Alpha-toxin; Community-associated MRSA; MRSA; Panton-Valentine leukocidin; Phenol-soluble modulin; Staphylococcus aureus.

Fig. 1. Evolution of CA-MRSA

The acquisition of SCCmec type IV (or V) by virulent strains appears to have been a common first step in the evolution of CA-MRSA strains. In some strains, as shown on the left, this combination may have been sufficient to produce highly virulent, methicillin-resistant strains with the capacity to infect healthy people, while in others, additional steps were required. These additional steps may have involved adaptations of gene expression, such as to enhance toxin production, and/or the uptake of MGEs, including or not including the acquisition of PVL-encoding genes. On the right, the assumed scenario for the evolution of USA300 is shown. Uptake of SCCmec type IV by a virulent ST8 strain resulted in a virulent MRSA strain (USA500), whose fitness was further improved by uptake of ACME. Acquisition of PVL-encoding genes appears to have increased virulence at least in some infection types.