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Seeing is understanding: Next generation chemical imaging for super-fast functional analyses of microbiomes

William Mong Distinguished Lecture by Prof Michael Wagner, University of Vienna, Austria
Oct 23, 2024

 

Date: November 13, 2024 (Wednesday)
Time: 16:00 - 17:00
Venue: Lecture Theatre A, G/F, Chow Yei Ching Building (CB-A), HKU
Speaker: Professor Michael Wagner, University of Vienna, Austria

Abstract:

One of the biggest challenges in environmental and medical microbiome research is to better understand functional properties of microbial community members at a single-cell level. Single-cell isotope probing has become a key tool for this purpose, but the current detection methods for determination of isotope incorporation into single cells do not allow high-throughput analyses. Recently, we developed an imaging-based approach termed stimulated Raman scattering-two-photon fluorescence in situ hybridization (SRS-FISH) for high-throughput metabolism and identity analyses of microbial communities with single-cell resolution (Ge et al. 2022 PNAS). SRS-FISH offers an imaging speed of 10 to 100 ms per cell, which is two to three orders of magnitude faster than achievable by state-of-the-art methods. We applied SRS-FISH together with quantitative microbiome profiling and long-read metagenomics to investigate the impact of the nervous system targeted drugs entacapone and loxapine succinate on the human gut microbiome (Pereira et al. 2024 Nature Microbiology). Ex vivo supplementation of physiologically relevant concentrations of entacapone or loxapine succinate to faecal samples significantly impacted the abundance of up to one third of the microbial species present. Importantly, we demonstrate with SRS-FISH that the impact of these drugs on microbial metabolism is much more pronounced than their impact on abundances, with low concentrations of drugs reducing the activity, but not the abundance of key microbiome members like Bacteroides, Ruminococcus or Clostridium species. We further demonstrate that entacapone impacts the microbiome due to its ability to complex and deplete available ferric iron, and that microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Remarkably, entacapone-induced iron starvation selected for iron-scavenging organisms carrying antimicrobial resistance and virulence genes. Collectively, these results unveil using next-generation chemical imaging the impact of two under-investigated drugs on whole microbiomes and identifies metal sequestration as a mechanism of drug-induced microbiome disturbance. In more general terms, SRS-FISH now provides a technology platform with which the activity of selected taxa in highly complex microbiomes can be determined precisely and in high throughput. This technology thus represents an important tool in our endeavours to decipher the functions and interactions of microbiomes and thus create the prerequisites for being able to manipulate them in a targeted manner.

About the speaker:
Michael Wagner is full professor for Microbial Ecology at the University of Vienna, Austria and a Distinguished Professor (20%) at Aalborg University, Denmark. He was the founding director of the Centre for Microbiology and Environmental System Science (CeMESS), which is a 2019 founded new faculty at the University of Vienna. His main research interests are single cell methods in microbiology and nitrogen-cycle microbiology. His team developed several innovative chemical imaging methods for directly studying functional properties of individual microbial cells within complex microbiomes. Recently, they spearheaded the application of these techniques to investigate drug-microbe interactions in the human gut. In the nitrogen cycle field, he discovered together with colleagues in 2015 complete nitrifying microbes (so-called comammox organisms) demonstrating that nitrification is not always a two-step process. Subsequently, they showed that comammox organisms are green nitrifiers producing much less nitrous oxide than classical ammonia-oxidizing bacteria. Michael Wagner has been continuously recognized as a highly cited scientist since 2014 and received an ERC Advanced Grant, the Wittgenstein and Schrödinger awards (the highest science awards in Austria), and the Jim Tiedje lifetime achievement award of the International Society for Microbial Ecology (ISME). In 2023 he became director of one of the seven Austrian Clusters of Excellence entitled "Microbiomes drive Planetary Health" in which 32 PIs from 8 leading Austrian research institutions focus on environmentally and medically relevant microbiomes.

All members of the HKU community and the general public are welcome to join. Seats for on-site participants are limited. Interested parties please register through the link below by 12 November 2024 0:00am: https://hkuems1.hku.hk/hkuems/ec_hdetail.aspx?guest=Y&ueid=97049 

A confirmation email will be sent to participants who have successfully registered.

We look forward to seeing you in the lecture. Thank you.