Dear Colleagues,

Professor Richard Proctor has significantly contributed to the field of persistent Staphylococcus aureus infections. These studies date back over 35 years, to the examination of ingestion of S. aureus by bovine endothelial cells (Vann JM and Proctor RA. Infect Innum. 55: 2155,1987). The final sentence in the abstract of this paper was prescient as a possible mechanism for persistent bacteremia: “Intracellular S.aureus would be continuously released into the circulation, possibly accounting for the persistent bacteremia that is found in S.aureus endovascular infections.” These studies led to an examination of lysis of endothelial cells by Hla (Vann JM and Proctor RA. Microb Pathogen 4: 443, 1988) and a search for naturally occurring non-lytic strains in the clinic. While we anticipated finding hla mutants, small colony variants (SCVs) were found instead. Of course, this resulted in decades of work on SCVs, with their description as a cause for persistent infections having been summarized in three reviews (Proctor RA et al. Naure Rev Microb 4: 295, 2006; Kahl BC et al. Clin Microb Rev 29: 401-427, 2016; Tuchshurr L et al. Front Microbiol 11: 1028, 2020). The observations that S. aureus was able to enter many types of host cells, hide from the immune system, resist antibiotics because of metabolic changes, and undergo SCV transformation was anticipated in early work; however, the number of mutations and pathways proliferated over the years.

Of course, the complex biology described in these two reviews continues to evolve. Many of the more recent observations are discussed in the papers in this Special Issue. Professor Proctor is justifiably proud of the large number of contributions made by his trainees and notes that this work could not have happened without their creativity and hard work. He would especially like to recognize and remember Professor Georg Peters, who was a close collaborator and dear friend who made so many contributions to the SCV work, especially establishing the clinical characteristics in large studies, then following this up with work on much of the cell biology of persistence. Our labs have worked continuously on this since.

The studies of the biochemical pathways that resulted in SCVs have also shed light on the biochemical pathways that produce antibiotic resistance. Thus, the study of SCVs has resulted in a better understanding of the mechanisms of bacterial antibiotic resistance.

Dr. Steven Projan
Prof. Dr. Barbara C. Kahl
Prof. Dr. Karsten Becker
Guest Editors

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