Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

Askarian, Fatemeh; Uchiyama, Satoshi; Valderrama, J. Andrés; Ajayi, Clement; Sollid, Johanna U. E.; Sorge, Nina M. van; Nizet, Victor; Strijp, Jos A. G. van; Johannessen, Mona

doi:10.1128/iai.00559-16

Cited by 43 publications

(31 citation statements)

References 46 publications

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“…Indeed, proteins of the Agr, Rot, Sae, Sar or Fur regulatory networks were differently expressed in all late isolates. Besides, SdrD, which plays a role in adhesion, invasion, and immune evasion [38], was up-regulated in late isolates of three patients. In addition, the protein SAUSA300_1236 (annotated as a CAP domain-containing protein of unknown function) was down-regulated in late isolates of three patients.…”

Section: Resultsmentioning

confidence: 99%

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Tan

Coureuil

Ramond

et al. 2018

Preprint

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BackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.

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Section: Resultsmentioning

confidence: 99%

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Tan

Coureuil

Ramond

et al. 2018

Preprint

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“…The viability of S. aureus in whole human blood was assessed and performed as previously described ( Askarian et al, 2017 ). Briefly, blood from healthy donors was collected in tubes containing hirudin (lepirudin; Roche, Switzerland), which is a specific inhibitor of thrombin thereby preventing coagulation without impairing complement activity.…”

Section: Methodsmentioning

confidence: 99%

“…The assay was performed as previously described using freshly isolated neutrophils ( Askarian et al, 2017 ). Briefly, bacteria were opsonized with 5% serum and incubated with neutrophils in RPMI/HSA at an MOI = 1.5 or MOI = 10.…”

Section: Methodsmentioning

confidence: 99%

Staphylococcus aureus Membrane-Derived Vesicles Promote Bacterial Virulence and Confer Protective Immunity in Murine Infection Models

et al. 2018

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Staphylococcus aureus produces membrane-derived vesicles (MVs), which share functional properties to outer membrane vesicles. Atomic force microscopy revealed that S. aureus-derived MVs are associated with the bacterial surface or released into the surrounding environment depending on bacterial growth conditions. By using a comparative proteomic approach, a total of 131 and 617 proteins were identified in MVs isolated from S. aureus grown in Luria-Bertani and brain-heart infusion broth, respectively. Purified S. aureus MVs derived from the bacteria grown in either media induced comparable levels of cytotoxicity and neutrophil-activation. Administration of exogenous MVs increased the resistance of S. aureus to killing by whole blood or purified human neutrophils ex vivo and increased S. aureus survival in vivo. Finally, immunization of mice with S. aureus-derived MVs induced production of IgM, total IgG, IgG1, IgG2a, and IgG2b resulting in protection against subcutaneous and systemic S. aureus infection. Collectively, our results suggest S. aureus MVs can influence bacterial–host interactions during systemic infections and provide protective immunity in murine models of infection.

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“…ClfA and SraP are involved in the pathogenesis of endocarditis. SdrD-mediated binding appears to help the bacteria survive in vivo ( Askarian et al, 2017 )—whether this is because of an increased ability to kill neutrophils and/or to invade cells is an open question. Also, unraveling whether internalization occurs via the same FAK/Src/PI3K/Akt cascade as for the FnBP-Fn-β1 integrin pathway is essential as this may offer a potential avenue to treat chronic infections.…”

Section: Staphylococcus Aureus Adhesion and Internalization mentioning

confidence: 99%

Staphylococcal Adhesion and Host Cell Invasion: Fibronectin-Binding and Other Mechanisms

2017

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Opportunistic bacteria from the genus Staphylococcus can cause life-threatening infections such as pneumonia, endocarditis, bone and joint infections, and sepsis. This pathogenicity is closely related to their capacity to bind directly to the extracellular matrix or to host cells. Adhesion is indeed the first step in the formation of biofilm or the invasion of host cells, which protect the bacteria from the host immune system and facilitate chronic infection. Adhesion relies on the expression of a repertoire of surface proteins called adhesins, notably microbial surface components recognizing adhesive matrix molecules. In this short review, we discuss the main pathway (FnBP-Fn-α5β1 integrin), as well as alternatives, through which Staphylococcus aureus adheres to and then invades non-professional phagocytic cells. We then examine the corresponding mechanisms for coagulase negative staphylococci. There is currently a little understanding of the molecular mechanisms that lead to internalization. Filling this gap in the literature would therefore be an important step toward limiting the duration of staphylococci infections in clinical practice.

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Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

Cited by 43 publications

References 46 publications

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence

Staphylococcus aureus Membrane-Derived Vesicles Promote Bacterial Virulence and Confer Protective Immunity in Murine Infection Models

Staphylococcal Adhesion and Host Cell Invasion: Fibronectin-Binding and Other Mechanisms

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