The surreptitious survival of the opportunistic pathogen <i>Staphylococcus lugdunensis</i> within macrophages as an immune evasion strategy
Bibliographic record
Abstract
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 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".