Editors' ChoiceInfectious Disease

Appreciating Staph Support

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Science Translational Medicine  11 Jul 2012:
Vol. 4, Issue 142, pp. 142ec121
DOI: 10.1126/scitranslmed.3004562

A Staphylococcus aureus bacterium can display either a Jekyll or Hyde personality, depending on its environment. In most people, S. aureus lives on the skin and in the nose, with no adverse effects. But these bacteria can transform to cause serious infections of the skin, bloodstream, joints, and heart tissue. These infections can be difficult to alleviate: A version known as methicillin-resistant S. aureus (MRSA) is among the most notorious drug-resistant bacteria and is sensitive to only one known antibiotic (vancomycin). Now, Schwartz and colleagues show that S. aureus aggregates into treatment-resistant biofilms only under certain conditions.

Biofilms are the predominant growth state for S. aureus in human infections. When attached to surfaces, S. aureus is more difficult to eradicate and more likely to accrue troublesome characteristics, such as antibiotic resistance. The authors show that S. aureus biofilms grown in peptone-NaCl-glucose (PNG) medium were more resistant to disassembly by protein-, DNA-, and polysaccharide-degrading enzymes than were those grown in tryptic soy broth. The PNG-grown biofilms contained extracellular fibers that bound S. aureus and phenol-soluble modulins (PSMs)—bacterial protein toxins that are part of the arsenal of agents produced by S. aureus in severe infections.

In a second dichotomy, however, PSMs also have been shown by researchers to exhibit antimicrobial activities. This potentially puzzling information was reconciled when the authors discovered that PSMs have dual functions. By examining PSM peptides under different conditions, the authors found that the toxins can have different secondary structures. In some conditions, PSMs are capable of forming amyloid fibers that promote bacterial attachment and biofilm formation, whereas in other conditions, PSMs take on an alpha helical structure and display biofilm disassembly and antimicrobial properties. The discovery that environmental conditions may influence the way PSM peptides fold and thus their biological activity may help to explain some of the contradictions in the field.

Better clinical protocols are desperately needed to treat and prevent S. aureus infections, especially MRSA. The finding that S. aureus uses αPSMs to form strong drug-resistant biofilms pinpoints a specific target for pharmaceutical development and provides insight into how S. aureus can develop resistance under specific growth conditions. Further studies are needed to determine whether targeted prevention of αPSM synthesis or protein assembly can successfully limit S. aureus aggregation in human tissues. If so, such targeted therapies may stem infections caused by the “Hyde” versions of S. aureus.

K. Schwartz et al., Functional amyloids composed of phenol-soluble modulins stabilize Staphylococcus aureus biofilms. PLoS Pathog. 8, e1002744 (2012). [Full Text]

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