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

Subject Area Clinical Infectiology and Tropical Medicine
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Term from 2023 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 519017205
 
Final Report Year 2025

Final Report Abstract

Vancomycin-resistant enterococci (VRE) are multidrug-resistant pathogens of great importance in human medicine that can cause serious infections. Infections with VRE usually occur endogenously, i.e. from the patient's own VRE colonized intestine. The significance of pathogenic factors of VRE for the developments of VRE infections is not fully understood. In a prospective study approach, the diversity of intestinal Enterococcus faecium colonization in patients with E. faecium bloodstream infection (BSI) was investigated. The intestinal colonization with only one clonal E. faecium strain was detected in 16 patients (66.6%). The parallel intestinal colonization with two different E. faecium strains was observed in 8 patients (33.3%). The BSI isolate was also found in the intestine in the majority of cases (n=19; 79%). The multilocus sequence typing (MLST) sequence types ST80 and ST117 were found in almost all patients. The low level of diversity of intestinal colonization with E. faecium suggests that infections are caused by a narrow spectrum of predominant E. faecium strains in the population studied. In order to investigate the role of the pathogen's own virulence factors for the development of VRE BSI, 120 clinical vancomycin-resistant Enterococcus faecium (VREfm) isolates from the blood of patients with VREfm BSI and intestinal VREfm colonization isolates from patients with a sole colonization of the intestine without BSI were sequenced and compared. Only the virulence gene fms-21 (pilA) showed a significant association with VREfm BSI (p=0.035). The analysis of other genes showed no significant association with VREfm BSI. Thus, a substantial influence of virulence genes on the development of VREfm BSI was not observed. The calculation of a predictive model for the development of VREfm BSI on the basis of associated virulence genes could therefore not be carried out as planned. Instead, it was investigated how the different VREfm sequence types are equipped with virulence genes and whether this equipment could be a possible explanation for the very successful epidemiological spread of the ST117 sequence type in Germany. For this purpose, a total of 187 VREfm isolates from patients with VRE BSI from all over NRW were sequenced and the identified sequence types (ST117, ST80, ST192, ST612, ST1299 and ST203) were compared with regard to the presence of virulence genes. The prevalence of virulence genes differed significantly in some cases depending on the sequence types. In particular, the sequence type ST117 showed the most extensive virulence genes. This supports the hypothesis that virulence genes could help explain the successful spread of ST117 in Germany.

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