PAS4AMR
Portable adaptive sequencing to detect AMR (PAS4AMR)
OBJECTIVE
We aim to design a technology for adaptive resistome sequencing to be used on innovative, low-cost, portable sequencing devices to enable surveillance of antimicrobial resistance (AMR) genes in low and middle-income countries (LMICs).
DESCRIPTION
Although the highest morbidity and mortality from AMR occurs in LMICs, there is lack of surveillance data on AMR from these countries. Consequently, the true nature and size of the AMR problem in these countries remains largely unknown and tailored measures for antimicrobial stewardship cannot be developed or applied. Genome sequencing and antimicrobial susceptibility testing are valuable tools for AMR surveillance, but they rely on lengthy, culture-based, procedures. Direct in-depth sequencing of microbial communities (metagenomics) allows the identification of etiological agents and AMR gene detection, even in culture-negative samples in real time. However, metagenomics sequencing is challenging because often the AMR genes are present at levels below the detection threshold. Recently, targeted metagenomics methods were therefore developed which can determine all genes related to AMR in a microbiome (the “resistome”). However, the currently used resistome enrichment methods rely on laborious and costly laboratory procedures and complicated bioinformatic analyses and Ilumina sequencing, which are not readily available in LMICs. Adaptive sequencing on Nanopore devices offers an alternative to laboratory-based enrichment procedures.
In this project we therefore propose to design an innovative technology for adaptive sequencing for AMR gene detection to be used on, low-cost, hand-held, Nanopore sequencing devices.
Ultimately, this technology will enable surveillance of AMR genes close to the point of care in LMICs and provide insights in the underlying mechanisms and spread of AMR and inform policies and guidelines for (empirical) treatment of infections. Eventually, this will reduce inappropriate exposure to antibiotics and improve clinical outcomes and, thus, contribute to curbing the AMR pandemic.
RESEARCH LEAD
Dr. Kristin Kremer, KNCV Tuberculosis Foundation (KNCV)
PARTNERS
Dr. Anita Schurch, Universitair Medisch Centrum Utrecht (UMCU)
Dr. Adri G.M. van der Zanden, Mozand bv
FUNDERS
The collaboration project is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.
COUNTRIES
A LMIC to be determined later (Kyrgyzstan, Tanzania or Vietnam)
The Netherlands