Unlatching of the Stem Domains in the Staphylococcus Aureus Leukocidin LukAB Influences Toxin Oligomerization

Staphylococcus aureus is a pathogen that utilizes a family of pore-forming toxins, leukocidins, to evade the host immune response and promote infection. Among these is leukocidin AB (LukAB), which engages host receptors to initiate pore formation on the host cell. The established cellular receptor for LukAB is CD11b. This study intoxicated CD11b-deficient cells with an alanine scanning library of CC8 LukAB to identify mutations that enable LukAB to exhibit full cytotoxicity in the absence of CD11b to understand the role of CD11b in the LukAB pore-forming process. To determine the role each receptor plays in the process of LukAB pore formation, mutations in CC8 LukAB was identified. In addition, an alanine scanning mutant library of CC8 LukA and LukB was generated, resulting in 615 constructs: 313 LukA mutants with wild-type (WT) LukB and 302 LukB mutants with a WT LukA. To compare stem domain flexibility between WT and the variants, hydroxyl radical footprinting-mass spectrometry was used on WT, V113A, and K120A LukAB. This dataset includes mass spectrometry data.