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Wednesday, January 18, 2023

MVIF.15 January23 Peer Bork

Full program of MVIF.15, 16 January 2023

MVIF.15 January23 Peer Bork

Environmental sequencing, that is metagenomics, has become a major driver for uncovering microbial biodiversity and increasingly also for cataloging molecular functions on our planet. Based on computational methods and resources, often developed in our group, but also utilizing public resources, here I (i) introduce into our work on the gut microbiome, arguable the best-studied microbial community with its internal and environmental (host) interactions, serving as a model for other habitats. Bioinformatics-driven hypothesis generation is complemented by experimental approaches in vitro, ex vivo and in vivo, to pave the way for diagnostics and medication guidance. I (ii) further show how to apply the underlying concepts to other habitats, like ocean and soil, to arrive at basic understanding of the underexplored microbial diversity on earth. Data integration from various habitats is crucial to address global base-line question utilizing the discovery of microbial biodiversity. For example, how is molecular function is evolving and spreading between habitats, given that species are mostly habitat-specific. Such base-line knowledge prepares the grounds, in analogy to microbial diagnostics and treatment for human health, for bioindicators and remediation strategies in various habitats towards improving planetary health.

Peer directs the Heidelberg site of EMBL (European Molecular Biology laboratory) and is senior group leader in the areas of computational biology and microbiomics. In addition, he is honorary professor at the universities of Heidelberg and Würzburg as well as the Fudan university of Shanghai. Peer received his PhD in Biochemistry (1990) and his Habilitation in Theoretical Biophysics (1995). His research group works in various areas of computational and systems biology, currently with a focus on microbiomes. He has published more than 650 research articles, among them more than 80 in Nature, Science or Cell, and is among the most cited researchers in the world (>320.000 citations, H-factor of 230 in 2022). He is or has been on the editorial board of various journals, including Science and Cell, and functions as founding editor of the journal Molecular Systems Biology. Peer co-founded five successful biotech companies, two of which went public. More than 60 of his former associates now hold professorships or other group leader positions in prominent institutions all over the world. He received a number of awards, among them the "Nature award for creative mentoring" for his achievements in nurturing and stimulating young scientists, the prestigious "Royal Society and Académie des Sciences Microsoft award" for the advancement of science using computational methods and the Novo Nordisk Foundation Novozymes prize for outstanding contributions to Biotechnology.  He further obtained two competitive ERC advanced investigator grants and is elected member of the German national academy of sciences (Leopoldina), the European Molecular Biology Organization (EMBO) and the Academia Europaea.

Selected talks

Investigation of antibiotic resistome in hospital wastewater during the COVID-19 pandemic: Is the Initial Phase of the Pandemic Contributing to Antimicrobial Resistance?

Since the COVID-19 pandemic started, there has been much speculation about how COVID-19 and antimicrobial resistance may be interconnected. In this study, untreated wastewater was sampled from Hospital A designated to treat COVID-19 patients during the first wave of the COVID-19 pandemic alongside Hospital B that did not receive any COVID-19 patients. Metagenomics was used to determine the relative abundance and mobile potential of antibiotic resistant genes (ARGs), prior to determining the correlation of ARGs with time/incidence of COVID-19. Our findings showed that ARGs resistant to macrolides, sulfonamides, and tetracyclines were positively correlated with time in Hospital A but not in Hospital B. Likewise, minor extended spectrum betalactamases (ESBLs) and carbapenemases of classes B and D were positively correlated with time, suggesting the selection of rare and/or carbapenem-resistant genes in Hospital A. This study highlighted concerns related to the dissemination of antimicrobial resistance (AMR) during the COVID-19 pandemic that may arise from antibiotic use and untreated hospital wastewater.

Link to OA paper:

Changzhi Wang, David Mantilla-Calderon, Yanghui Xiong, Mohsen Alkahtani, Hamed Al Qarni, Yasir Bachawri, Peiying Hong

Presenting author affiliation: King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

Human gut microbiome-dependent energy-extraction

More than 15 years ago, it was hypothesised that the gut microbiota could causally affect weight gain due to the gut microbiome’s capacity to extract energy from the diet. Yet, evidence linking microbiome-dependent energy harvest to particular human gut microbiome compositions have been lacking. In this recently published study, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and structure. We found opposite of what we expected that stool energy density was positively associated with intestinal transit time. Furthermore, individuals with a Bacteroides enterotype (B-type) had significantly lower energy left in faeces (per gram dried faeces) compared to individuals with a Ruminococcaecea enterotype (R-type). The B-type individuals had lower alpha-diversity and faster intestinal transit time, but also a significantly higher body weight compared to the R-type individuals. Furthermore, markers of proteolytic fermentation were increased in the R-type compared to the B-type. Together, this could suggest that human gut microbiome-dependent energy extraction is diversified according to intestinal transit time and gut microbiome ecosystem variations as reflected by enterotypes. While the causalities remain to be established, the observations are intriguing and could provide new dietary strategies in body weight management.

Link to OA paper:

Henrik Roager

Presenting author affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark

Exposure to environmental stressors decreases the resilience of river microbial communities towards invasion by foreign resistant bacteria

The release of wastewater treatment plant effluents into rivers exposes the river microbiome to a high load of antibiotic resistant bacteria (ARB) along with complex mixtures of abiotic pollutants acting as stressors.
To understand the proliferation of antimicrobial resistance (AMR) it is crucial to determine the factors that govern invasion of ARB into the river microbiome. Consequently, we here aim at elucidating how the resilience of the resident microbial communities against invasion by foreign ARB is affected by co-released stressors.

To achieve this, we grew natural microbial biofilms on glass slides in rivers for one month. The biofilms were then transferred to laboratory, recirculating flume systems and exposed to a single pulse of a model resistant invader bacterium (E. coli) either in presence or absence of stress induced by Cu2+. The invasion dynamics of E. coli into the biofilms were then monitored for 14 days. Despite an initially successful introduction of E. coli into the biofilms, independent of the imposed stress, over time the invader perished in absence of stress. However, under stress the invading strain successfully established and proliferated in the biofilms. Noteworthy, the increased establishment success of the invader coincided with a loss in microbial community diversity under stress conditions, likely due to additional niche space becoming available for the invader.

In conclusion, we demonstrate that the intrinsic resilience of the river microbiome towards invasion by ARB is strongly linked with maintaining diversity and that co-exposure to stressors that disrupt community diversity and structure increases long-term invasion success.

Link to OA paper:

Kenyum Bagra, Thomas Berendonk, Gargi Singh, Uli Klümper

Presenting author affiliation: Technische Universität Dresden, Institute of Hydrobiology, Dresden, Germany; Department of Civil Engineering, Indian Institute of Technology, Roorkee, Uttarakhand, India

Metatranscriptomics - Unlocking microbial activity from complex samples

The Ribo-Zero Plus Microbiome Depletion Kit offers an RNA-to-analysis workflow solution for metatranscriptomic research. The Ribo-Zero Plus Microbiome depletion probe sets reduce unwanted rRNA reads from stool and other complex  samples therefore increasing RNA reads of interest. In addition, the compli­mentary analysis software democratizes this method for both experienced and new microbiome users. The focus on analyzing high-value portions of the transcriptome allows deeper insight into active gene function in the microbiome.

Nitzan Soffer

Presenting author affiliation: Sr. Product Manager, Infectious Disease & Microbiology, Illumina