The surreptitious survival of the opportunistic pathogen Staphylococcus lugdunensis within macrophages as an immune evasion strategy

Staphylococcus lugdunensis has acquired recognition as a relatively new and serious pathogen that is often clinically misidentified as S. aureus . To cause infection S. lugdunensis must circumvent host immunity, including the innate defenses presented by professional phagocytes such as macrophages. In this study, we demonstrate for the first time that macrophages of murine and human origin are not microbicidal towards S. lugdunensis and that phagocytosed S. lugdunensis remain viable within infected macrophages over an extended period (>24 h). Interestingly, phagocytosed S. lugdunensis, which fail to replicate, also do not intoxicate host cells, thus distinguishing the intracellular lifestyle of S. lugdunensis from that of S. aureus . Dextran pulse‐chase and LAMP‐1 immuno‐localization studies reveal that phagocytosed S. lugdunensis take up residence inside LAMP‐1‐positive phagolysosomes where the bacteria persist for at least 24 hours. Phagocytosed S. lugdunensis are modified within macrophages such that they are sensitized to in vitro stresses imposed by antimicrobial peptide treatment (e.g. polymyxin B), exposure to non‐ionic detergent (e.g. Triton‐X100), and the staphylococcal selective medium mannitol salt agar. We further demonstrate that optimal survival of S. lugdunensis requires O‐acetylated peptidoglycan since a S. lugdunensis oatA mutant, which is more sensitive to killing by lysozyme than WT, survived to a lesser extent in the phagosome. Through pharmacological disruption of lysosome function, either prior to or post phagocytosis, we demonstrate that S. lugdunensis bacteria can be coaxed into escaping the phagolysosome and replicating within both murine macrophages and primary human macrophages. Notably, however, intracellularly replicating S. lugdunensis fail to intoxicate infected macrophages as indicated by the host cells' ability to phagocytose IgG‐opsonized targets and remain refractory to vital dye staining. We propose that macrophages harboring S. lugdunensis in vivo represent a bacterial reservoir and events that disrupt macrophage function would allow these bacteria to proliferate whilst remaining protected from extracellular immune factors. Support or Funding Information Canadian Institutes of Health Research This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .