Københavns Universitet

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MSc. til studier af biologisk rolle af CRISPR-Cas i Staphylococcus aureus at Københavns Universitet

S. aureus is a serious human pathogen but also a natural colonizer of both humans and animals. Over the recent years there has been an increasing number of human infections with S. aureus strains originating from livestock and being resistant to methicillin (MRSA)(1). One clone belonging to this group carries a CRISPR-Cas type III-A system (2). In general, CRISPR-Cas systems are rare in S. aureus and but surprisingly a few strains have the system and in those it is located together with the gene encoding resistance to methicillin (3). Therefore, we are interested in investigating the biological role of the CRISPR-Cas type III-A in livestock MRSA strains. The project will involve:

  1. Assessment of CRISPR-Cas activity against phages and plasmids: We have phages and plasmids targeted by the system and will search for conditions where targeting is most efficient
  2. Assessment of conditions that impact expression of cas genes: Constructing a reporter fusion to cas1 and cas6 and use this to minor response to a broad range of condtions including phage infection and antibiotic exposure
  3. Preliminary data suggest that the CRISR-Cas activity may be impacted by the staphylococcal quorum sensing system (4): We will examine how mutants lacking the quorum sensing system impacts CRISPR-Cas activity and vice versa using existing mutants
  4. We anticipate that the CRISPR-Cas system may be mobile between staph strains: We will examine mobility by transduction and by other means
  5. Since type III-A systems targets RNA we speculate that there may be a gene regulatory role of CRISPR-Cas in S. aureus: We will examine the impact of CRISPR-Cas on global gene expression by comparing CRISPR-Cas mutant with wild type cells by RNAseq

If you are interested, please contact:

Hanne Ingmer, hi@sund.ku.dk or Janine Bowring (janine.bowring@sund.ku.dk)

References:

  1. Vestergaard M, Frees D, Ingmer H. Antibiotic Resistance and the MRSA Problem. Microbiol Spectr. 2019 Mar;7(2). doi: 10.1128/microbiolspec.GPP3-0057-2018. PMID: 30900543.
  2. Cao, L., et al., Identification and functional study of type III-A CRISPR-Cas systems in clinical isolates of Staphylococcus aureus. Int J Med Microbiol, 2016. 306(8): p. 686-696.
  3. Larsen, J., et al., Staphylococcus aureus CC395 harbours a novel composite staphylococcal cassette chromosome mec element. J Antimicrob Chemother, 2017. 72(4): p. 1002-1005.
  4. Gless BH, Bojer MS, Peng P, Baldry M, Ingmer H, Olsen CA. Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation. Nat Chem. 2019 May;11(5):463-469. doi: 10.1038/s41557-019-0256-3. Epub 2019 Apr 22. PMID: 31011175.
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