Kliniken & Institute … Institute Zentrum für… Medizinische… Forschung Research Nurjadi

Research Group Nurjadi

Group Leader:

Dr. Dennis Nurjadi

Curriculum Vitae

PROJECTS

1) Impact and Determinants of Staphylococcus aureus Colonization and Infection

Staphylococcus aureus as commensal and pathogen has gained enormous attention over the last few years, because of increasing virulence, antimicrobial resistance, and the epidemic occurrence of associated infections. The human skin and mucosae are the primary reservoir of S. aureus. Persistently colonized individuals have been shown to be at a high risk of acquiring a range of S. aureus related diseases – from skin and soft tissue infection to sepsis. Besides, it is known that persistent carriage plays a role in the dispersion of S. aureus in the environment and promotes the development of resistance against antibiotics through horizontal genetic exchange followed by selection of resistant clones under antibiotic pressure. Taken together, colonization is a key factor for the evolution of infection and antimicrobial resistance.

The host-factors promoting S. aureus colonization are largely enigmatic. Antimicrobial peptides (AMP) as part of the primary skin defense are thought to play a key role in shaping the human skin microbiome. Human β-Defensin-3 (hBD-3) and RNase7 are highly active against S. aureus in vitro and are constitutively expressed in healthy, non-inflamed skin, but can be induced through various stimuli. Interestingly, there is inter-individual variation in AMP-expression suggesting that mechanisms involved in AMP regulation are important determinants of S. aureus colonization.

Our group focuses on the role of innate immune mechanisms as determinant for colonization and infection with S. aureus. Previously, we have shown that lower expression of hBD-3 and RNase7 increases susceptibility of human skin to S. aureus colonization and infection. Current projects study the interplay of cell-mediated immunity and AMP expression in human skin and try to identify those pathways that account for the inter-individual variation in AMP-expression in human skin and keratinocytes. We use a combination of in vitro models, human in vivo and ex vivo experiments as well as genetic association studies to provide comprehensive evidence on both, the functional and population relevance of involved host-factors.

2) Mechanisms, Transmission and spread of antimicrobial resistance

Emergence of carbapenem resistance in gram negative bacilli is an on-going problem. Besides the limited availability of alternative antibiotics, plasmid mediated resistance is transmissible and has been known to cause outbreaks in clinical settings. Conjugation is considered as the most important transfer mechanism of resistance plasmids between gram negative bacilli. During hospitalization many patients exhibit not only a single carbapenem-resistant species, but also multiple carbapenem-resistant species. The gut microbiome provides the perfect condition and environment for horizontal gene transfer. However,  the exact driving factors of horizontal gene transfer are yet to be elucidated. In this project, our group will focus on in vivo transfer of carbapenemase genes using next generation sequencing and transcriptomic approach to investigate interspecies plasmid transfer and antibiotic pressure.

Molecular epidemiology of antibiotic resistance, especially of multi-resistant gram-negatives, is a secondary focus of our group. Better knowledge of the local and global epidemiology of antibiotic resistance has a major impact on patient care.

Closely linked to this work are studies on the emergence and global spread of antimicrobial resistant S. aureus through colonized and infected travellers. These research projects are conducted in collaboration with a network of researchers at travel clinics across Europe and microbiologists around the globe. For further information on the European Network on Imported S. aureus, please visit the network’s homepage at www.staphtrav.eu.

Group members

Kaan Kocer
Quang Vinh Ngo
Monja Menz
Julius Hannesen
Carolin Bootsveld
Nicole Henny
Delal Sahin

ASSOCIATE MEMBERS:

Philipp Zanger
Sabine Gabrysch

FUNDING

DZIF (German Center for Infection Research, BMBF)
  • 8000-402-2 TE-39Clinical Leave Program (Tübingen)
  • MD Stipends (2014, 2018)

DFG (German Research Foundation)

  • DFG NU403/1-1     “Burden of S. aureus colonization as risk factor for colonization”

Selected publications

Complete list of publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=Nurjadi+dennis+OR+nurjadi+d

Impact and Determinants of Staphylococcus aureus Colonization and Infection
  1. Nurjadi D, Heeg K, Weber ANR, Zanger P. (2018) Toll-like receptor 9 (TLR-9) promotor polymorphisms and gene expression are associated with persistent Staphylococcus aureus nasal carriage. Clin Microbiol Infect. 2018 Nov;24(11):1210.e7-1210.e12
  2. Nurjadi D, Kain M, Marcinek P, Gaile M, Heeg K, Zanger P (2016). Ratio of T-Helper Type 1 (Th1) to Th17 Cytokines in Whole Blood Is Associated With Human β-Defensin 3 Expression in Skin and Persistent Staphylococcus aureus Nasal Carriage. J Infect Dis. 2016 Dec 1;214(11):1744-1751.
  3. Nurjadi D, Herrmann E, Hinderberger I, Zanger P (2013) Impaired β-defensin expression in human skin links DEFB1 promoter polymorphisms with persistent Staphylococcus aureus nasal carriage Journal of Infectious Diseases 207:666-74
  4. Zanger P, Nurjadi D, Vath B, Kremsner PG (2011) Persistent nasal carriage of Staphylococcus aureus is associated with deficient induction of human beta-defensin 3 after sterile wounding of healthy skin in vivo. Infections and Immunity 79(7):2658-62

Mechanisms, Transmission and spread of antimicrobial resistance

  1. Nurjadi D, Fleck R, Lindner A, Schäfer J, Gertler M, Mueller A, Lagler H, Van Genderen PJJ, Caumes E, Boutin S, Kuenzli E, Gascon J, Kantele A, Grobusch MP, Heeg K, Zanger P; StaphTrav Network (2019). Import of community-associated, methicillin-resistant Staphylococcus aureus to Europe through skin and soft-tissue infection in intercontinental travellers, 2011-2016. Clin Microbiol Infect. 2019 Jun;25(6):739-746
  2. Nurjadi D, Friedrich-Jänicke B, Schäfer J, Van Genderen PJ, Goorhuis A, Perignon A, Neumayr A, Mueller A, Kantele A, Schunk M, Gascon J, Stich A, Hatz C, Caumes E, Grobusch MP, Fleck R, Mockenhaupt FP, Zanger P (2015). Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe. Clin Microbiol Infect. 2015 Jun;21(6):567.e1-10
  3. Nurjadi D, Olalekan AO, Layer F, Shittu AO, Alabi A, Ghebremedhin B, Schaumburg F, Hofmann-Eifler J, Van Genderen PJ, Caumes E, Fleck R, Mockenhaupt FP, Herrmann M, Kern WV, Abdulla S, Grobusch MP, Kremsner PG, Wolz C, Zanger P (2014). Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe. J Antimicrob Chemother. 2014 Sep;69(9):2361-8.
  4. Zanger P, Nurjadi D, Schleucher R, Scherbaum H, Wolz C, Kremsner PG, Schulte B (2012) Import and spread of Panton-Valentine Leukocidin-positive Staphylococcus aureus through nasal carriage and skin infections in travelers returning from the tropics and subtropics. Clinical Infectious Diseases 54:483-92