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Dear Editor, In the present study, we show that the development of Staphylococcus aureus device-associated infection involves mutations in the quorum-sensing system Agr that increase biofilm formation and thereby bacterial resistance to antibiotics.The enormous difficulty clinicians face in the treatment of device-associated infections is due to the characteristic involvement of biofilms, which are bacterial agglomerations that form on the device surface and exhibit considerably increased resistance to virtually all types of antibiotics. 1 One of the most frequent causes of deviceassociated infections is Staphylococcus aureus, which is also infamous for its exceptional recalcitrance towards antibiotic treatment. 2,3 How device-associated infections develop remains incompletely understood. This is in part since only end-point isolates from clinical deviceassociated infection are usually investigated. Main questions that remain include whether a device-associated infection is only caused by a selection of strains that are particularly pronounced biofilm formers or whether adaptations increasing biofilm formation occur during infection, and if so, which among them play a dominant role for that adaptation.To answer these questions, we compared sequential isolates from cases of prolonged S. aureus surgical implant infection obtained at our hospital (See Figure S1 for selection of isolates). In all cases, initial (T1) samples were taken after infection had developed post-surgery, and secondary (T2) samples were collected when recurrence or persistence of infection was diagnosed (Table S1). All bacterial samples from the T1 and T2 time points were classified as S. aureus by appearance and mass spectrometry. Remarkably, all T1 isolates were homogenously hemolytic on sheep blood agar plates, whereas all T2 samples were homogenously non-hemolytic (Figure 1A). One representative clone of each sample was stored, and all stored T1 and T2 isolates were confirmed to exhibit a hemolyticThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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