Annually 31.5 million people develop sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection. Approximately 5.3 million people die yearly due to sepsis, among them 420,000 neonates. The majority of epidemiological studies on sepsis, or blood stream infections, focus either on bacteria or fungi and combined analyses are sparse. A global point prevalence study that included 13,796 adult hospitalised patients from 75 countries reported 7,087 infected subjects and 4,947 (70%) had positive blood culture. Gram-positive bacteria were mostly encountered (62%), followed by Gram-negative bacteria (47%) and fungi (19%). In May 2017, the World Health Assembly –which is the WHO’s decision-making entity– adopted a resolution to improve sepsis prevention, diagnosis and management.

Since decades automated blood culture is the gold standard in routine sepsis diagnostics. However, up to one third of the blood cultures remain negative, even in the highly suspected cases. Typically a blood culture needs to be incubated for five to ten days for bacteria and fungi, respectively. When positive, a culture on solid media needs to be made to identify the pathogen. Thereafter antibiotic susceptibility testing needs to be performed, which further delays targeted therapy with several days.

Molecular routine diagnostic platforms are the current state of the art in rapid sepsis-causing pathogen detection and identification.7,8 There are, however, several major drawbacks:

i) these platforms rely on blood culture; ii) they shorten only the post-blood culture identification procedure; iii) novel pathogens and resistance mechanisms are overlooked; iv) the number of pathogenic cells is extremely low (1 cell/ml blood); v) the sensitivity relies mostly on the nucleic acid extraction.

Antimicrobial peptides (AMPs), especially cyclic and glycosylated variants (cgAMPs), bind specifically to microorganisms and are known to have a diverse mode of action in the human body. There are thousands of natural AMPs known, which are nowadays increasingly in the spotlights due to the decreasing effectiveness of antibiotics. The deployment of peptides in treatment of infections is one of the newly explored routes to overcome the increasing antibiotic resistance. A class of peptides that has raised interest are the food-derived bioactive agents, especially the human lactoferrins.

We aim to drastically improve microbial disease diagnostics using the novel approach of a peptide-coated biosensor for pathogen enrichment from complex matrices, by taking Candida sepsis as a model. Ultimately, enriched microbial cells can be used for culture- and nucleic acids diagnostics. This approach decreases diagnostic-time from many days to a few hours. At this TRL3 stage we want to optimise lactoferrin peptides by modify cysteine residues for targeted attachment of Candida yeasts and site-specific orientation to link peptides to a biosensor-surface.