Bacterial Survival Amidst an Immune Onslaught The Contribution of the Staphylococcus aureus Leukotoxins.docVIP

Pearls BacterialSurvivalAmidstanImmuneOnslaught:The ContributionoftheStaphylococcusaureusLeukotoxins FrancisAlonzoIII,VictorJ.Torres* DepartmentofMicrobiology,NewYorkUniversitySchoolofMedicine,NewYork,NewYork,UnitedStatesofAmerica The success of Staphylococcus aureus as a human pathogen is influencedbyitsabilitytoelaboratefactorsthatpreventinfection resolution by the host immune system. Such immune-altering arthritis and endophthalmitis [16,17], recent evidence from Malachowa and colleagues suggests a role for this toxin in bloodstream infection [18]. Together, these data indicate leuko- toxinslikelycontributetomultipleS.aureusdiseasestatesinvivo. FutureinvestigationintothecontributionofeachleukotoxintoS. aureuspathogenesisusingmultipleinfectionconditionsandanimal models will serve to delineate each toxin’s capacity to promote disease. factors include complement inhibitory molecules, antibody binding proteins, super-antigens, as well as potent cytolytic peptides and pore-forming toxins. Here, we discuss one class of immune cell-targeting toxins, the bi-component leukotoxins. These toxins are believed to form octameric oligomers of alternating subunits on the surface of host cells and insert b- barrel pores into cell membranes leading to osmotic imbalance and cell lysis [1]. We will discuss the reemerging interest in leukotoxins as potent virulence factors with defined cellular targets, the implications of their lethal and sublethal cellular effects,aswellaschallengesthathaverestrictedunderstandingof their functional activity in vivo, while emphasizing areas of interest for future exploration. In addition, we highlight studies supporting the development of antileukotoxin antibodies and immunization strategies as potential modalities to counter S. aureus infection. ChallengingthePropositionofStrictFunctional Redundancy S. aureus leukotoxins exhibit lytic activity on host neutrophils, although some have greater perceived potency than others (Figure 1). Ea