Abstract
Staphylococcus aureus continues to be a public health threat, especially in hospital settings. Studies aimed at deciphering the molecular and cellular mechanisms that underlie pathogenesis, host adaptation, and virulence are required to develop effective treatment strategies. Numerous host-pathogen interactions were found to be dependent on phosphatases-mediated regulation. This study focused on the analysis of the role of the low-molecular weight phosphatase PtpB, in particular, during infection. Deletion of ptpB in S. aureus strain SA564 significantly reduced the capacity of the mutant to withstand intracellular killing by THP-1 macrophages. When injected into normoglycemic C57BL/6 mice, the SA564 ΔptpB mutant displayed markedly reduced bacterial loads in liver and kidney tissues in a murine S. aureus abscess model when compared to the wild type. We also observed that PtpB phosphatase-activity was sensitive to oxidative stress. Our quantitative transcript analyses revealed that PtpB affects the transcription of various genes involved in oxidative stress adaptation and infectivity. Thus, this study disclosed first insights into the physiological role of PtpB during host interaction allowing us to link phosphatase-dependent regulation to oxidative bacterial stress adaptation during infection.
Highlights
Given the impact of Ptp homologues on survival within macrophages [24,40], we wondered whether PtpB might fulfill similar functions in S. aureus
In vitro growth curves performed with the wild type, the mutant and the complemented strain demonstrated that the deletion of ptpB in S. aureus SA564 did not markedly affect the bacterial growth in Tryptic Soy Broth (TSB) (Figure 1a), which is in line with earlier observations made with
Our macrophage survival, mice infection, and transcription data the bacterial cell in the macrophage phagolysosome
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Staphylococcus aureus has emerged as a major human pathogen responsible for hospital and community-associated infections that can involve almost any organ system, including skin and soft tissue infections, necrotizing pneumonia, and infective endocarditis [1]. The increase in multi-resistant variants of this species, coupled with its increasing prevalence as a nosocomial pathogen, is of major concern [2]. The success of S. aureus as a pathogen and its ability to cause such a wide range of infections are the result of its large armamentarium of virulence factors that is controlled by a sophisticated network of regulatory molecules [3,4]
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