168 Chapter 8 isolates from persistent MRSAB patients differed in several characteristics. First, the persistent MRSAB isolates were more resistant to killing by hNP-1, an antimicrobial peptide produced by neutrophils. Second, they discovered that persistent MRSAB isolates were more adept at binding to fibrinogen and fibronectin, which are thought to act as the anchors allowing S. aureus to establish endovascular infection. Third, multiplex genotyping identified the genes cna, sdrD, and sfrE more frequently in persistent MRSAB isolates compared to resolving MRSAB isolates. However, another larger study using the same definition of persistent MRSAB (cultures positive >7 days) was unable to find differences in the presence of virulence factor genes (including sdrD) or agr dysfunction [22]. Similarly, Seidl et al. did not note any differences in fibronectin binding between persistent versus resolving MRSAB isolates [77]. These inconsistencies between studies may highlight epidemiological differences between SAB isolates from different geographic centers. Phenotypic variability of SAB isolates While genotypic analysis has been extremely informative in differentiating persistent MRSAB from resolving MRSAB isolates, often the downstream effects on function are a result of multiple interacting processes. Following on from Xiong et al.’s work discussed in Section 3.2, Seidl et al. performed several in vitro studies to distinguish functional differences between isolates from patients with persistent MRSAB vs. resolving MRSAB [77]. They again confirmed that persistent MRSAB isolates exhibited significantly less killing by the neutrophil-derived AMP hNP-1 (p = 0.02) and plateletderived thrombin-induced platelet microbicidal proteins (tPMPs, p = <0.001). Other findings from the study noted no significant difference in overall biofilm biomass produced, but they did report biofilms from persistent MRSAB isolates contained a lower carbohydrate content (58.4% vs. 30.6%; p = 0.04). It is thought that plateletderived antimicrobial peptides, such as tPMPs, play a key role in assisting clearance of S. aureus in the bloodstream, particularly around areas of endothelial damage that are thought to serve as an anchor in the establishment of an endovascular infection [78]. S. aureus isolates exhibiting decreased killing by tPMPs in-vitro show increased virulence in an in vivo rabbit endocarditis model [66,79]. Furthermore, S. aureus bloodstream isolates from patients with confirmed endovascular infections were less susceptible than bacteremia strains without an endovascular source [67,68]. It is reassuring to see the clinical relevance of the in vitro studies by establishing the relationship between decreased tPMPs killing and persistent MRSAB [16,76]. The relationship between decreased hNP-1 killing and persistence is less well established but could be a result of increased survival inside neutrophils after phagocytosis [76,77].
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