Abstract
Staphylococcus lugdunensis is a coagulase negative Staphylococcus recognized as a virulent pathogen. It is responsible for a wide variety of infections, some of which are associated with biofilm production, such as implanted medical device infections or endocarditis. However, little is known about S. lugdunensis regulation of virulence factor expression. Two-component regulatory systems (TCS) play a critical role in bacterial adaptation, survival, and virulence. Among them, LytSR is widely conserved but has variable roles in different organisms, all connected to metabolism or cell death and lysis occurring during biofilm development. Therefore, we investigated here the functions of LytSR in S. lugdunensis pathogenesis. Deletion of lytSR in S. lugdunensis DSM 4804 strain did not alter either susceptibility to Triton X-100 induced autolysis or death induced by antibiotics targeting cell wall synthesis. Interestingly, ΔlytSR biofilm was characterized by a lower biomass, a lack of tower structures, and a higher rate of dead cells compared to the wild-type strain. Virulence toward Caenorhabditis elegans using a slow-killing assay was significantly reduced for the mutant compared to the wild-type strain. By contrast, the deletion of lytSR had no effect on the cytotoxicity of S. lugdunensis toward the human keratinocyte cell line HaCaT. Transcriptional analyses conducted at mid- and late-exponential phases showed that lytSR deletion affected the expression of 286 genes. Most of them were involved in basic functions such as the metabolism of amino acids, carbohydrates, and nucleotides. Furthermore, LytSR appeared to be involved in the regulation of genes encoding known or putative virulence and colonization factors, including the fibrinogen-binding protein Fbl, the major autolysin AtlL, and the type VII secretion system. Overall, our data suggest that the LytSR TCS is implicated in S. lugdunensis pathogenesis, through its involvement in biofilm formation and potentially by the control of genes encoding putative virulence factors.
Highlights
Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci (CoNS) family
Our results demonstrate that LytSR plays a significant role in the biofilm formation of S. lugdunensis, probably in connection with cell death and metabolism
Transcriptional analyses have shed new light on the putative virulence factors of S. lugdunensis that could be regulated by LytSR
Summary
Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci (CoNS) family. S. lugdunensis native valve endocarditis can be aggressive and destructive, often requiring surgery (Anguera et al, 2005). It can cause a wide range of infections such as abscesses and wound infections (Böcher et al, 2009; Heldt Manica and Cohen, 2017), bone and joint infections (Argemi et al, 2017b), and infections associated with catheters or implanted medical devices (Nesher et al, 2017). The pathogeny of S. lugdunensis appears in many infections to be related to biofilm formation within host tissues or indwelling medical devices (Frank and Patel, 2007; Argemi et al, 2017a). The resulting infections are usually difficult to treat because biofilm protects bacteria from both the host’s immune system and the antimicrobial therapies (Stewart and Costerton, 2001; Lebeaux et al, 2014)
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