RAPIDS: Resistance assessment and pathogen ID by antibody-based detection systems
The RAPIDS research group, led by Dr. Alexander Klimka, develops antibody-based rapid tests for the detection of pathogens and clinically relevant antibiotic resistance factors. The acronym RAPIDS stands for "Resistance assessment and pathogen ID by antibody-based detection systems." The group aims to enable the rapid and reliable detection of clinically relevant pathogens and antibiotic resistance factors directly at the point of care, thereby supporting targeted treatment as well as appropriate infection prevention and control measures. To this end, the group has established a platform for generating monoclonal antibodies against a range of microbial targets and subsequently developing lateral flow assays (LFAs) based on these antibodies. Suitable targets for these rapid tests are identified in close collaboration with Dr. Paul Higgins, other DZIF researchers, and industry partners. The tests are designed to provide results rapidly without the need for complex laboratory infrastructure, making them particularly suitable for point-of-care diagnostics. This approach has already resulted in commercially available diagnostic products developed in collaboration with the Belgian company Coris BioConcept.
Within RAPIDS, antibody-based rapid tests are being developed for various applications, including the detection of antibiotic resistance factors. These easy-to-use and cost-effective lateral flow assays (LFAs) do not require complex laboratory equipment for the actual test procedure and are designed to provide results rapidly at the point of care. Such tests are therefore particularly suitable for use in physicians’ offices, nursing homes, or countries with limited access to specialized diagnostic laboratories. Early detection of resistance factors in patient samples can help guide appropriate infection control measures and the selection of targeted anti-infective therapy. An important prerequisite for point-of-care use, however, is that patient samples such as swabs, blood, or urine can be prepared rapidly and easily for testing.
In collaboration with the Belgian company ↗ Coris BioConcept, the group is currently developing a rapid test for the detection of the vancomycin resistance factors VanA and VanB in vancomycin-resistant Enterococcus faecium (VRE). Further approaches include the detection of hypervirulent Klebsiella pneumoniae, the screening of Pseudomonas aeruginosa isolates in the context of immunotherapies, and the diagnosis of sexually transmitted infections such as Neisseria gonorrhoeae.
Established workflow for the development of LFA prototypes: First, suitable target proteins are identified and analyzed using bioinformatics. The selected target genes are then cloned in E. coli, expressed as recombinant proteins, and purified. The purified proteins are used to immunize mice according to established protocols and to generate hybridoma cells producing monoclonal antibodies (mAbs). The mAbs are subsequently purified and analyzed for specificity and binding affinity before being used to develop LFA prototypes, which are then evaluated in practice. Following successful testing, diagnostic products are developed from the prototypes in collaboration with an industry partner for the healthcare market and gradually integrated into clinical practice.
The successful translation of this approach into practical application is demonstrated by the commercially available LFAs OXA-23 K-SeT® (2018) and the follow-up test RESIST ACINETO (2022), both developed in collaboration with Coris BioConcept for the detection of carbapenemases in Acinetobacter baumannii. ↗ RESIST ACINETO detects four important carbapenemases—OXA-23, OXA-40, OXA-58, and NDM—within 15 minutes. These enzymes break down carbapenems, indicating to the treating physician that this class of antibiotics is ineffective for the patient. The test detects more than 95 percent of carbapenem resistance in A. baumannii infections.
