The role of virulence genes in the development of invasive infections caused by vancoymcin-resistant enterococci (VRE)

• Applicant: Dr. Christian Wilhelm Böing
• Subject Area: Clinical Infectiology and Tropical Medicine ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 519017205

Vancomycin-resistant enterococci (VRE) are nosocomial pathogens with increasing prevalence worldwide. Infections with VRE are mostly endogenous, i.e. by VRE isolates that colonize the patient's intestine. To date, clinical risk factors for the development of VRE infections have been identified, however only a small proportion of (risk) patients with VRE colonization actually experience VRE infection. Some patients are known to be colonized with more than one genetically identical VRE isolate at a time. However, which pathogen-associated factors contribute to the translocation of certain VRE variants from colonization to infection is scarcely known . In this study, we would like to investigate the hypothesis that certain genes or gene clusters promote translocation from VRE colonization to VRE infection.To test our hypothesis, we propose the following work program: 1. In a prospective study section, we would like to investigate the diversity of rectal enterococcal colonization in patients with enterococcal BSI. Based on the sequencing of multiple isolates from one anal or rectal swab, it will be possible to estimate how frequently multiple colonization with different enterococcal strains occurs in patients with BSI. In the case of multiple colonization, we want to answer the question if colonization-infection translocation occurs through a dominant strain or also non-dominant strains. The VRE isolates will be sequenced by whole genome sequencing and analyzed for genetic relatedness by core genome multilocus sequence typing (cgMLST) sequence typing. Furthermore, virulence genes and antibiotic resistance genes will be compared. 2. In parallel, we would like to investigate the association of virulence genes with the development of BSI in a second retrospective study section. For this purpose, we would like to use available VRE isolates isolated from the bloodstream of different patients with a VRE bloodstream infection (BSI) or from the anal or rectal swab of subjects without a VRE BSI. Subsequently, the sequence data will be analyzed for the presence of virulence genes associated with the development of BSI. 3. Based on the identified virulence genes associated with the development of BSI, a statistical model will be developed to further investigate the predictive significance of several virulence genes.The aim of this study is to better predict the risk of invasive infections in VRE-colonized patients. In the long term, this may help to apply advanced hygiene measures such as isolation, screening and disinfection more rationally and depending on the actual virulence of VRE.

• DFG Programme: Research Grants