Polyamine Resistance Key to MRSA Survival in the Skin

A team of microbiologists has discovered the molecular mechanism that allows the USA300 strain of methicillin-resistant Staphylococcus aureus (MRSA) to survive in the acidic environment of the skin that kills other strains of the organism.

Investigators at the University of North Carolina (Chapel Hill, USA) found after analysis of the genomes of many hundreds of MRSA strains that only the USA300 strain possessed a block of 34 genes, called the arginine catabolic mobile element (ACME). The activity of the ACME genes gave the bacteria a survival advantage by protecting them from polyamines in the skin. Polyamines, which are toxic to most bacteria, are critical to wound repair, as they are anti-inflammatory and promote tissue regeneration.

The investigators selectively mutated and inactivated the individual ACME components. They reported in the January 16, 2013, issue of the journal Cell Host & Microbe that one gene, SpeG, was critical due to the activity of its polyamine-resistant enzyme product that was essential for neutralizing excess host polyamines. SpeG activity was shown to be required for USA300 survival in a mouse model. Furthermore, transfer of the SpeG gene to MRSA strains other than USA300 enhanced their ability to survive in the mouse model.

"Previously, the field tried to understand MRSA by focusing on attributes that we already knew were important, such as the amount of toxins or virulence factors a given strain makes. Those elements may explain why the disease is so bad when you get it, but they do not explain how a particular strain takes over. Our work uncovers the molecular explanation for one strain's rapid and efficient spread to people outside of a crowded hospital setting," said senior author Dr. Anthony Richardson, assistant professor of microbiology and immunology at the University of North Carolina. "The problem is by the time you figure out how one strain comes into dominance, it often fades away and a new strain comes in. But because these compounds occur naturally and are so toxic, we still think they can lead to treatments that are effective against all MRSA. We will just have to put in a little extra work to block the gene and make this particular strain of MRSA susceptible to polyamines."

Related Links:
University of North Carolina