Inactivation of the response regulator AgrA has a pleiotropic effect on biofilm formation, pathogenesis and stress response in Staphylococcus lugdunensis
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PROVIDER: PRJNA753717 | ENA |
REPOSITORIES: ENA
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Project description:Exploration of the the transcriptomic consequences of the complete deletion of agrA gene in Staphylococcus lugdunensis. Overall, the ΔagrA deletion significantly affected the expression of 400 genes. Among them, 149 were upregulated and 251 were downregulated.
2021-08-16 | GSE181857 | GEO
Project description:Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: ∆argA mutant colonies were white while the parental strains were slightly yellow. Compared to the wild-type strain, the ∆argA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of ∆agrA was significantly reduced by the addition of 10 % NaCl or 0.4 mM H2O2 and its survival after 2 h in presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the ∆agrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the ∆agrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the ∆RNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.
2022-02-22 | PXD028347 | Pride
Project description:Staphylococcus lugdunensis is a coagulase negative Staphylococcus, recognized as a virulent pathogen. It is responsible for a wide variety of infections, some of which being associated with biofilm production, such as implanted medical devices infections or endocarditis. However, little is known about S. lugdunensis virulence regulation. Two-component regulatory systems (TCS) play critical roles in bacterial adaptation, survival and virulence. Among them, LytSR is widely conserved, but has variable roles in different organisms, all being connected to metabolism or cell death and lysis into biofilms. Therefore, we investigated here the functions of LytSR in S. lugdunensis pathogenesis. Deletion of lytSR in S. lugdunensis DSM 4804 strain did not alter neither the susceptibility to Triton X-100 induced autolysis nor the 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 towards Caenorhabditis elegans using slow-killing assay was significantly reduced for the mutant compared to the wild-type strain. In contrast, the deletion of lytSR had no effect on S. lugdunensis cytotoxicity towards 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 metabolism of amino acid, carbohydrates and nucleotides. Furthermore, LytSR appeared to be involved in the regulation of genes coding 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 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.
2019-11-06 | GSE139909 | GEO
Project description:Staphylococcus lugdunensis is a coagulase-negative Staphylococcus part of the commensal skin flora but emerge as an important opportunistic pathogen. Because iron limitation is a crucial stress during infectious process, we performed phenotypic study and compared proteomic profiles of this species incubated in absence and in presence of the iron chelator 2,2'-dipyridyl (DIP). No modification of cell morphology nor cell wall thickness were observed in presence of DIP. However iron-limitation condition promoted biofilm formation and reduced the ability to cope with oxidative stress (1 mM H2O2). In addition, S. lugdunensis N920143 cultured with DIP was significantly less virulent in the larvae of Galleria mellonella model of infection than that grown under standard conditions. We verified that these phenotypes were due to an iron limitation by complementation experiments with FeSO4. By mass spectrometry after trypsin digestion, we characterized the first iron-limitation stress proteome in S. lugdunensis. Among 1426 proteins identified, 349 polypeptides were differentially expressed. 222 were more and 127 less abundant in S. lugdunensis incubated in iron-limitation condition, and by RT-qPCR, some of the corresponding genes have been shown to be transcriptionally regulated. Our data revealed that proteins involved in iron metabolism and carriers were over-expressed, as well as several ABC transporters and polypeptides linked to cell wall metabolism. Conversely, enzymes playing a role in the oxidative stress response (especially catalase) were repressed. This phenotypic and global proteomic study allowed characterization of the response of S. lugdunensis to iron-limitation. We showed that iron-limitation promoted biofilm formation, but decrease the oxidative stress resistance that may, at least in part, explained the reduced virulence of S. lugdunensis observed under low iron condition.
2020-10-13 | PXD021832 | Pride
Project description:Using RNAseq approach, we performed global a transcriptomic analysis of cells incubated in absence and in presence of iron chelator in Staphylocuccus lugdunensis. 175 genes were identified as members of the iron-limitation stimulon (127 up- and 48 down-regulated).
2021-02-10 | GSE166487 | GEO
Project description:Staphylococcus lugdunensis overview
| PRJNA42457 | ENA
Project description:The present study deals with the cross-talk of polysaccharide biosynthesis pathways of a highly infectious intracellular pathogen Francisella tularensis, the causative agent of tularemia. We have studied the consequences of disrupting the FTS_1402 gene that lies within the putative polysaccharide locus FTT0789-FTT0800 on production of glycoconjugates and host-pathogen associated properties. Based on the homology to campylobacterial PglK flippase, FTS_1402 was predicted to play a role in glycosylation as a transporter of the nascent glycan across the inner membrane before its addition to target protein. Surprisingly, an inactivation of FTS_1402 gene had a pleiotropic effect upon production of multiple surface glycoconjugates. We show that FTS_1402 encoded protein is required for complete glycosylation but also for biogenesis of other surface exopolysaccharides such as lipopolysaccharide, capsule and/or capsule-like complex. All monitored glycoconjugates had preserved structures but were synthesized in lower amounts when compared to the highly virulent parental strain. Inactivation of FTS_1402 had an unexpectedly marked impact on virulence of the mutant, which however, provided protection against subsequent systemic challenge. With particular respect to protein glycosylation in the mutant and a wild type FSC200 strain, we here provide relevant MS data.
2016-02-04 | PXD002123 | Pride
Project description:Genome sequencing and assembly of Staphylococcus lugdunensis
| PRJNA589350 | ENA
Project description:Staphylococcus lugdunensis VCU150 Genome sequencing
| PRJNA53783 | ENA
Project description:Staphylococcus lugdunensis VCU148 Genome sequencing
| PRJNA53779 | ENA