Fluorescence in situ hybridization (FISH) as a diagnostic tool in infectious diseases: translational insights for diagnostic histopathology

In the diagnostic histopathology of infectious diseases, histological examination may, in addition to demonstrating inflammation - reveal structures in clinical specimen that are morphologically compatible with microorganisms. However, it is often difficult to ascertain whether those structures indeed represent bacteria or fungal pathogens and to determine their exact identity. In addition, findings from histopathology and medical microbiology are not always congruent, since different areas of a specimen are typically investigated by the respective disciplines. Here, we present FISHseq – the combination of Fluorescence in situ hybridization in combination with PCR and sequencing – as a tool to bridge the gap between histopathology, microbiology and molecular pathogen detection. FISHseq visualizes and identifies microorganisms in situ , even on the identical sample slide to be used for histopathology. Moreover, FISH reveals the living mode of the microorganisms, i.e. if they grow in hard-to-detect and hard-to-treat biofilms. This review describes how the method has been translated from a research technique in environmental microbiology into an accredited, quality-controlled diagnostic tool in medical microbiology and highlights recent developments. In the future, FISHseq may galvanize traditionally separate disciplines such as histopathology and microbiology by enabling integrated interpretation of tissue specimens and advancing tissue-based diagnostics of infectious diseases.