PhD project by Katrine Højholt Iversen

Name: Katrine Højholt Iversen
Project Title: Genomic and metagenomic analysis of microbial agents causing infective endocarditis
Group: BMEM
Supervisor(s): Anders Gorm Pedersen, Simon Rasmussen, Xiaohui Chen Nielsen

Project description:

Infective endocarditis (IE) is an infection of the inner layer of the heart or the heart valves. Gram-positive cocci of the genera Staphylococcus, Streptococcus, and Enterococcus account for more than 80% of all IE cases. In rare cases, other microbial agents, such as Aerococcus spp. can cause the infection as well.

IE is a relatively rare disease with two to ten incidents per 100,000 individuals per year in the general population world-wide. However, the mortality of IE is between 15-20%, and one-year mortality approaches 40%. Therefore, IE is a severe infectious disease, as it involves long term hospitalization and heart surgery in 50% of the cases.

This thesis includes five studies, and its main focus is IE caused by Mitis group streptococci (MGS) and Aerococcus ssp.. The majority of the MGS are commensal colonizers of the human oral cavity, where they can have beneficial effects on the oral health of the host. However, this group of oral bacteria can escape their niche and in rare cases, cause infectious diseases such as IE.

Collectively, the thesis provided an insight into the nature of MGS. For correct species identification, we showed that multi-locus sequence analysis involving seven genes provided enough genetic variability to generate distinct phylogenetic clusters. We furthermore identified genes that could be associated with virulence; genes associated with host colonization and modulation of the host immune system were identified in the S. mitis, S. oralis, S. sanguinins, S. gordonii, ancient Streptococcus DNA, and in two Aerococcus species. The same level of virulence genes was identified in the ancient Streptococcus DNA as in modern oral samples. Interestingly, we found no genetic differences between strains isolated from patients with IE and the oral cavity of healthy individuals. Altogether, our findings illustrate the complexity of the role of these bacteria in IE etiology, where they all, most likely, carry a pathogenic potential.

Kontakt

Anders Gorm Pedersen
Gruppeleder, Professor
DTU Sundhedsteknologi