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- Title
Staphylococcus aureus persistence in osteocytes: weathering the storm of antibiotics and autophagy/xenophagy.
- Authors
Gunn, Nicholas J.; Kidd, Stephen P.; Solomon, Lucian B.; Yang, Dongqing; Roscioli, Eugene; Atkins, Gerald J.
- Abstract
Staphylococcus aureus is a major causative pathogen of osteomyelitis. Intracellular infections of resident bone cells including osteocytes can persist despite goldstandard clinical intervention. The mechanisms by which intracellular S. aureus evades antibiotic therapy are unknown. In this study, we utilised an in vitro S. aureus infection model of human osteocytes to investigate whether antibioticmediated dysregulation of autophagy contributes to this phenomenon. Infected or non-infected osteocyte-like cells were exposed to combinations of rifampicin, vancomycin, and modulators of autophagy. Intracellular bacterial growth characteristics were assessed using colony-forming unit (CFU) analysis, viable bacterial DNA abundance, and the rate of escape into antibiotic-free medium, together with measures of autophagic flux. Rifampicin, alone or in combination with vancomycin, caused a rapid decrease in the culturability of intracellular bacteria, concomitant with stable or increased absolute bacterial DNA levels. Both antibiotics significantly inhibited autophagic flux. However, modulation of autophagic flux did not affect viable bacterial DNA levels. In summary, autophagy was shown to be a factor in the host--pathogen relationship in this model, as itsmodulation affected the growth state of intracellular S. aureus with respect to both their culturability and propensity to escape the intracellular niche. While rifampicin and vancomycin treatments moderately suppressed autophagic flux acutely, this did not explain the paradoxical response of antibiotic treatment in decreasing S. aureus culturability whilst failing to clear bacterial DNA and hence intracellular bacterial load. Thus, offtarget effects of rifampicin and vancomycin on autophagic flux in osteocyte-like cells could not explain the persistent S. aureus infection in these cells.
- Subjects
OSTEOCYTES; AUTOPHAGY; BACTERIAL DNA; ANTIBIOTICS; BONE cells; INTRACELLULAR pathogens
- Publication
Frontiers in Cellular & Infection Microbiology, 2024, p1
- ISSN
2235-2988
- Publication type
Article
- DOI
10.3389/fcimb.2024.1403289