The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction
Ontology highlight
ABSTRACT:
ORGANISM(S): Pseudomonas aeruginosa PA14
PROVIDER: GSE81065 | GEO | 2016/09/29
SECONDARY ACCESSION(S): PRJNA320399
REPOSITORIES: GEO
Similar Datasets
Project description:The host protein calprotectin inhibits the growth of a variety of bacterial pathogens through metal sequestration in a process known as 'nutritional immunity'. Staphylococcus aureus growth is inhibited by calprotectin in vitro and calprotectin is localized in vivo to staphylococcal abscesses during infection. However, the staphylococcal adaptations that provide defense against nutritional immunity and the role of metal-responsive regulators are not fully characterized. In this work, we define the transcriptional response of S. aureus and the role of the metal-responsive regulators, Zur, Fur, and MntR, in response to metal limitation by calprotectin exposure. Additionally, we identified genes affecting the fitness of S. aureus during metal limitation through a Transposon sequencing (Tn-seq) approach. Loss of function mutations in clpP, which encodes a proteolytic subunit of the ATP-dependent Clp protease, demonstrate reduced fitness of S. aureus to the presence of calprotectin. ClpP contributes to pathogenesis in vivo in a calprotectin-dependent manner. These studies establish a critical role for ClpP to combat metal limitation by calprotectin and reveal the genes required for S. aureus to outcompete the host for metals.
2024-05-14 | GSE266003 | GEO
Project description:The host protein calprotectin inhibits the growth of a variety of bacterial pathogens through metal sequestration in a process known as 'nutritional immunity'. Staphylococcus aureus growth is inhibited by calprotectin in vitro and calprotectin is localized in vivo to staphylococcal abscesses during infection. However, the staphylococcal adaptations that provide defense against nutritional immunity and the role of metal-responsive regulators are not fully characterized. In this work, we define the transcriptional response of S. aureus and the role of the metal-responsive regulators, Zur, Fur, and MntR, in response to metal limitation by calprotectin exposure. Additionally, we identified genes affecting the fitness of S. aureus during metal limitation through a Transposon sequencing (Tn-seq) approach. Loss of function mutations in clpP, which encodes a proteolytic subunit of the ATP-dependent Clp protease, demonstrate reduced fitness of S. aureus to the presence of calprotectin. ClpP contributes to pathogenesis in vivo in a calprotectin-dependent manner. These studies establish a critical role for ClpP to combat metal limitation by calprotectin and reveal the genes required for S. aureus to outcompete the host for metals.
2024-05-14 | GSE265954 | GEO
Project description:Microorganisms form biofilms containing differentiated cell populations. To determine factors driving differentiation, we study protein distributions in bacterial biofilms using shotgun proteomics. Notably, zinc- and manganese-depleted portions of the biofilm repress the production of anti-staphylococcal molecules. Exposure to calprotectin (a host protein known to sequester metal ions at infectious foci) recapitulates responses occurring within metal-deplete portions of the biofilm and promotes interaction between P. aeruginosa and Staphylococcus aureus. Consistent with these results, the presence of calprotectin promotes co-colonization of the murine lung, and polymicrobial communities are found to co-exist in calprotectin-enriched airspaces of a cystic fibrosis lung explant. These findings, which demonstrate that metal fluctuations are a driving force of microbial community structure, have clinical implications because of the frequent occurrence of P. aeruginosa and S. aureus co-infections.
2016-06-22 | PXD004081 | Pride
Project description:Calprotectin (CP) inhibits bacterial viability through extracellular chelation of transition metals. However, how CP influences general metabolism remains largely unexplored. We show here that CP restricts bioavailable Zn and Fe to the pathogen Acinetobacter baumannii, inducing an extensive multi-metal perturbation of cellular physiology. Detailed here are the RNA sequencing files of WT A. baumannii ATCC 17978 grown plus or minus recombinant human calprotectin.
2019-03-26 | GSE125491 | GEO
Project description:The intestines house a diverse microbiota that must compete for nutrients to survive, but the specific limiting nutrients that control pathogen colonization are not clearly defined. Clostridioides difficile colonization typically requires prior disruption of the microbiota, suggesting that outcompeting commensals for resources is key in establishing C. difficile infection (CDI). The immune protein calprotectin (CP) is released into the gut lumen during CDI to chelate zinc (Zn) and other essential nutrient metals. Yet, the impact of Zn limitation on C. difficile colonization is unknown. To define C. difficile responses to Zn limitation, we performed RNA sequencing on C. difficile exposed to CP. In media with CP, C. difficile upregulated genes involved in metal homeostasis and amino acid metabolism.
2019-10-24 | GSE135912 | GEO
Project description:Pseudomonas aeruginosa and Staphylococcus aureus are often co-isolated in persistent infections. The goal of this study was to determine how secreted products from S. aureus affect gene expression in P. aeruginosa. Therefore, media control or S. aureus supernatant was added to P. aeruginosa cultures at 25% total volume and gene expression was measured at 20 min, 1 h, and 2 h using RNA-seq. Overall, after addition of S. aureus supernatant, there was an upregulation in genes involved in metal deprivation and intermediate metabolite uptake.
2022-05-18 | GSE185963 | GEO
Project description:To combat infections, the mammalian host limits availability of essential transition metals such as iron (Fe), zinc (Zn), and manganese (Mn) in a strategy termed “nutritional immunity”. The innate immune protein calprotectin (CP) contributes to nutritional immunity by sequestering these metals to exert antimicrobial activity against a broad range of microbial pathogens. One such pathogen is Pseudomonas aeruginosa, which causes opportunistic infections in vulnerable populations including individuals with cystic fibrosis. CP was previously shown to withhold Fe(II) and Zn(II) from P. aeruginosa and induce Fe- and Zn-starvation responses in this pathogen. In this work, we performed quantitative, label-free proteomics to further elucidate how CP impacts metal homeostasis pathways in P. aeruginosa. We report that CP induces an incomplete Fe-starvation response, as many Fe-containing proteins that are repressed by Fe limitation are not affected by CP treatment. The Zn-starvation response elicited by CP seems to be more complete than the Fe-starvation response and includes increases in Zn transporters and Zn-independent proteins. CP also induces the expression of membrane-modifying enzymes, and metal-depletion studies indicate this response results from the sequestration of multiple metals. Moreover, the increased expression of membrane-modifying enzymes upon CP treatment correlates with increased tolorance to polymyxin B. Thus, response of P. aeruginosa to CP treatment includes both single and multi-metal starvation responses and includes many factors related to virulence potential, broadening our understanding of this pathogen’s interaction with the host.
2021-07-29 | PXD027638 | Pride
Project description:The goal of this study is to correlate the transcriptional response of S. aureus cells grown in Calprotectin treated medium with that of cells grown in Mn or Zn depletion conditions. Keywords: RNA sample Staphylcoccus aureus strain Newman was grown to mid-log phase in Calprotectin treated medium or medium lacking either Zn or Mn. RNA was isolated, labeled and hybridized to an S. aureus Affymetrix GeneChip. Biological replicates are indicated as A, B, or C.
2010-05-26 | E-GEOD-9828 | biostudies-arrayexpress
Project description:To determine whether calprotectin can elicit any transcriptional response in the probiotic E. coli Nissle 1917(EcN), EcN was treated with 200 ug/g of calprotectin in log phase.
2023-08-16 | GSE211418 | GEO
Project description:The goal of this study is to correlate the transcriptional response of S. aureus cells grown in Calprotectin treated medium with that of cells grown in Mn or Zn depletion conditions. Keywords: RNA sample
2008-02-01 | GSE9828 | GEO