Reactivation of dormant lumbar methicillin-resistant Staphylococcus aureus osteomyelitis after 12 years

Stevens, Qualls E.; Seibly, Jason; Chen, Ying H.; Dickerman, Rob D.; Noel, Jerry; Kattner, Keith A.

doi:10.1016/j.jocn.2005.12.006

Cited by 19 publications

(10 citation statements)

References 21 publications

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“…Consequently, bacteria can persist inside host cells for months or even years and induce only a low-grade inflammation and limited clinical signs 8,21 . The relapse can occur many months after the initial episode, even in immunocompetent patients 19 . In this work, using the model of long-term intracellular S. aureus infection we detected bacteria within the cytoplasm and in vacuoles in agreement with the previous report 45 .…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus induces DNA damage in host cell

Deplanche

Mouhali

Nguyen

et al. 2019

Sci Rep

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Staphylococcus aureus causes serious medical problems in human and animals. Here we show that S. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AX phosphorylation, a marker of DNA double strand breaks (DSBs), in human cervix cancer HeLa and osteoblast-like MG-63 cells. This DNA damage is mediated by alpha phenol-soluble modulins (PSMα 1–4 ), while a specific class of lipoproteins (Lpls), encoded on a pathogenicity island in S. aureus , dampens the H2AX phosphorylation thus counteracting the DNA damage. This DNA damage is mediated by reactive oxygen species (ROS), which promotes oxidation of guanine forming 7,8-dihydro-8-oxoguanine (8-oxoG). DNA damage is followed by the induction of DNA repair that involves the ATM kinase-signaling pathway. An examination of S. aureus strains, isolated from the same patient during acute initial and recurrent bone and joint infections (BJI), showed that recurrent strains produce lower amounts of Lpls, induce stronger DNA-damage and prompt the G2/M transition delay to a greater extent that suggest an involvement of these mechanisms in adaptive processes of bacteria during chronicization. Our findings redefine our understanding of mechanisms of S. aureus -host interaction and suggest that the balance between the levels of PSMα and Lpls expression impacts the persistence of the infection.

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Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus induces DNA damage in host cell

Deplanche

Mouhali

Nguyen

et al. 2019

Sci Rep

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“…Despite the combination of adequate surgical treatment and an optimally prolonged course of antimicrobial chemotherapy, these infections are associated with a high rate of relapse and can evolve to a chronic disease (Osmon et al, 2013;Tande and Patel, 2014). Indeed, many clinical observational studies have demonstrated that S. aureus BJIs can persist asymptomatically before relapse occurs months or years after the initial episode, even in immunocompetent hosts (Greer and Rosenberg, 1993;Bosse et al, 2005;Stevens et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Adaptive processes ofStaphylococcus aureusisolates during the progression from acute to chronic bone and joint infections in patients

Trouillet‐Assant

Lelièvre

Martins-Simões

et al. 2016

Cellular Microbiology

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Staphylococcus aureus bone and joint infection (BJI) is associated with significant rates of chronicity and relapse. In this study, we investigated how S. aureus is able to adapt to the human environment by comparing isolates from single patients with persisting or relapsing BJIs that were recovered during the initial and recurrent BJI episodes. In vitro and in vivo assays and whole-genome sequencing analyses revealed that the recurrent isolates induced a reduced inflammatory response, formed more biofilms, persisted longer in the intracellular compartments of host bone cells, were less cytotoxic and induced less mortality in a mouse infection model compared with the initial isolates despite the lack of significant changes at the genomic level. These findings suggest that S. aureus BJI chronicization is associated with an in vivo bacterial phenotypical adaptation that leads to decreased virulence and host immune escape, which is linked to increased intraosteoblastic persistence and biofilm formation.

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“…The invasion of host cells by S. aureus eventually leads to the formation of an intracytoplasmic reservoir, where bacteria remain protected from the action of cell- and antibody-mediated immune response and from that of most antimicrobial agents. This bacterial sanctuarisation makes successful treatment even more challenging and paves the way for infection relapse [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus

et al. 2011

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BackgroundStaphylococcus aureus is a well-armed pathogen prevalent in severe infections such as endocarditis and osteomyelitis. Fibronectin-binding proteins A and B, encoded by fnbA/B, are major pathogenesis determinants in these infections through their involvement in S. aureus adhesion to and invasion of host cells. Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics, frequently occurring in vivo because of impaired drug diffusion at the infection site, can alter S. aureus phenotype. We therefore investigated their impact on S. aureus fibronectin-mediated adhesiveness and invasiveness.MethodsAfter in vitro challenge of S. aureus 8325-4 and clinical isolates with sub-MICs of major anti-staphylococcal agents, we explored fnbA/B transcription levels, bacterial adhesiveness to immobilised human fibronectin and human osteoblasts in culture, and bacterial invasion of human osteoblasts.ResultsOxacillin, moxifloxacin and linezolid led to the development of a hyper-adhesive phenotype in the fibronectin adhesion assay that was consistent with an increase in fnbA/B transcription. Conversely, rifampin treatment decreased fibronectin binding in all strains tested without affecting fnbA/B transcription. Gentamicin and vancomycin had no impact on fibronectin binding or fnbA/B transcription levels. Only oxacillin-treated S. aureus displayed a significantly increased adhesion to cultured osteoblasts, but its invasiveness did not differ from that of untreated controls.ConclusionOur findings demonstrate that several antibiotics at sub-MICs modulate fibronectin binding in S. aureus in a drug-specific fashion. However, hyper- and hypo- adhesive phenotypes observed in controlled in vitro conditions were not fully confirmed in whole cell infection assays. The relevance of adhesion modulation during in vivo infections is thus still uncertain and requires further investigations.

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Reactivation of dormant lumbar methicillin-resistant Staphylococcus aureus osteomyelitis after 12 years

Cited by 19 publications

References 21 publications

Staphylococcus aureus induces DNA damage in host cell

Staphylococcus aureus induces DNA damage in host cell

Adaptive processes ofStaphylococcus aureusisolates during the progression from acute to chronic bone and joint infections in patients

Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus

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