The host cell membrane attacking toxins of Staphylococcus aureus and their roles beyond host cell lysis.

(A) Phagocytosis of invading bacteria is followed by fusing of the phagosome to the lysosome, resulting in destruction of the bacteria. S. aureus alpha (α) and phenol-soluble modulin (PSM) toxins inhibit fusing of the lysosome. This enables the bacteria to escape from the phagosome into the cytoplasm, allowing intracellular niche establishment and replication. (B) PSM toxins target cohabiting bacterial species within established niches, aiding in competition for resources and competitive exclusion of nonkin isolates. (C) PSM toxins have surfactant properties in vitro, enabling sliding movement across agar surfaces in the absence of traditional mobility structures such as flagella and pili. (D) Pore-forming toxins are involved at each step of S. aureus biofilm formation. During the initial cell attachment phase, alpha-toxin is involved in establishing cell-to-cell contacts, enabling the formation of secondary biofilm structures. In the later stages of the biofilm lifestyle, extracellular matrices develop, surrounding the cells within the biofilm. In the presence of extracellular DNA (eDNA), beta-toxin covalently cross-links with itself, adding to this extracellular nucleoprotein biofilm matrix and contributing to the formation of complex biofilm secondary structuring. Detachment from the mature biofilm allows for dispersal to new sites of infection. PSM toxins are involved in this stage of the biofilm lifestyle, aiding release of cell clusters from the main body of the biofilm.