Phenol-soluble modulins (PSMs) are a family of small proteins, that carry out a variety of functions, including acting as toxins, assisting in biofilm formation, and colony spreading. PSMs are produced by Staphylococcus bacteria including Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermidis. Many PSMs are encoded within the core genome and can play an important virulence factor. PSMs were first discovered in S. epidermidis by Seymour Klebanoff via hot-phenol extraction and were described as a pro-inflammatory complex of three peptides. Since their initial discovery, numerous roles of PSMs have been identified. However, due in part to the small size of many PSMs, they have largely gone unnoticed until recent years.

Although PSMs are present in every Staphylococcal species, there is still diversity. Staphylococcus aureus encodes eight different PSMs, PSMα 1-4, PSMβ 1-2, PSMγ (Also known as δ-toxin in S. aureus), and PSM-mec. While Staphylococcus epidermidis encodes one PSMα, PSMβ 1-2, PSMγ, and PSM-mec. In addition S. epidermidis encodes two unique PSMs, PSMδ and PSMε.

PSM-mec is one of the most widely encoded PSMs among Staphylococcal species, which may be in part due to PSM-mec being encoded on the mecI mobile genetic element.

As the PSM classes are closely related there are many conserved aspects. However each PSM class plays a different role, as such there are some distinctive features for each. Generally, PSMs are encoded on the core genome of staphylococcal species. However, some such as PSM-mec are encoded on mobile genetic elements. PSMs are generally separated into one of two classes α-type PSMs and β-type PSMs, which are based upon characteristics of the two most well studied PSMs PSMα and PSMβ.

PSMα forms an amphipathic α-helix structure that composes the entire length of the peptide. These peptides are relatively short, being composed of only 20-25 amino acids. With regard to charge, α-type PSMs generally have a neutral charge, but may also be slightly positive.

PSMβ are similar to PSMα in that they contain an amphipathic α-helix. However, the helix does not compose the entirety of the peptide, instead covering only the C-terminus of the peptide. PSMβ are generally larger than PSMα, being composed of 43-45 amino acids. Unlike α-type PSMs, β-type PSMs usually possess a negative charge.

PSMγ (also known as δ-Toxin) shares some homology with PSMα-3 encoded by S. aureus.

PSMδ is encoded downstream of the PSMα gene in S. epidermidis. In addition PSMδ shares some homology with PSMγ.