Dr Rene Niehus
|Research Area:||Bioinformatics & Stats (inc. Modelling and Computational Biology)|
|Technology Exchange:||Computational biology and Medical statistics|
|Scientific Themes:||Tropical Medicine & Global Health and Clinical Trials & Epidemiology|
|Keywords:||Antimicrobial-resistance, Multi-drug resistance, Mathematical modelling, Statistical modelling, ESBLs, Bacteraemia, Infection control, Bayesian statistics and Microbiome|
Rene Niehus works as a postdoctoral research fellow at the Mahidol-Oxford Tropical Medicine Research Unit (Bangkok), but he is based at the Lao-Oxford-Mahosot Hospital Wellcome Research Unit (LOMWRU) in Vientiane, Laos.
For the evidence-based use of antibiotics, probiotics, and faecal microbiota transplants it is key to have a detailed understanding of the population-level processes, as well as of the dynamic processes within the human microbiome, which include species-species interactions, the spread of plasmids and phages and selection by the host-immune system. This understanding requires merging different disciplines, including evolutionary biology, microbioly and ecology.
Rene finished his PhD at the University of Oxford studying social evolution within bacterial communities. His current research focus is to understand the spread of antibiotic resistance genes both within and between human hosts. In his current work, Rene studies how antibiotic treatment affects the resistance gene abundance in the GI tract of single patients over time. He also studies to what extend multi-drug resistant bloodstream infections are adding to, instead of replacing, non-resistant infections. This is an important question in order to determine the burden of resistant infections.
In his work, Rene uses mathematical and computational modelling such as Bayesian modelling and machine learning.
|Professor Ben Cooper||Tropical Medicine||Oxford University, Bangkok||Thailand|
|Professor Paul Newton||Tropical Medicine||Oxford University, Vientiane||Laos|
|Dr David AB Dance||Tropical Medicine||Oxford University, Vientiane||Laos|
|Mr Olivier Celhay||Tropical Medicine||Oxford University, Bangkok||Thailand|
|Dr Mayfong Mayxay||Tropical Medicine||Oxford University, Vientiane||Laos|
|Dr Celine Caillet||Tropical Medicine||Oxford University, Vientiane||Laos|
Microbes have the potential to be highly cooperative organisms. The archetype of microbial cooperation is often considered to be the secretion of siderophores, molecules scavenging iron, where cooperation is threatened by "cheater" genotypes that use siderophores without making them. Here, we show that this view neglects a key piece of biology: siderophores are imported by specific receptors that constrain their use by competing strains. We study the effect of this specificity in an ecoevolutionary model, in which we vary siderophore sharing among strains, and compare fully shared siderophores with private siderophores. We show that privatizing siderophores fundamentally alters their evolution. Rather than a canonical cooperative good, siderophores become a competitive trait used to pillage iron from other strains. We also study the physiological regulation of siderophores using in silico long-term evolution. Although shared siderophores evolve to be downregulated in the presence of a competitor, as expected for a cooperative trait, privatized siderophores evolve to be upregulated. We evaluate these predictions using published experimental work, which suggests that some siderophores are upregulated in response to competition akin to competitive traits like antibiotics. Although siderophores can act as a cooperative good for single genotypes, we argue that their role in competition is fundamental to understanding their biology.
Horizontal gene transfer is central to microbial evolution, because it enables genetic regions to spread horizontally through diverse communities. However, how gene transfer exerts such a strong effect is not understood. Here we develop an eco-evolutionary model and show how genetic transfer, even when rare, can transform the evolution and ecology of microbes. We recapitulate existing models, which suggest that asexual reproduction will overpower horizontal transfer and greatly limit its effects. We then show that allowing immigration completely changes these predictions. With migration, the rates and impacts of horizontal transfer are greatly increased, and transfer is most frequent for loci under positive natural selection. Our analysis explains how ecologically important loci can sweep through competing strains and species. In this way, microbial genomes can evolve to become ecologically diverse where different genomic regions encode for partially overlapping, but distinct, ecologies. Under these conditions ecological species do not exist, because genes, not species, inhabit niches.
Microbes produce many compounds that are costly to a focal cell but promote the survival and reproduction of neighboring cells. This observation has led to the suggestion that microbial strains and species will commonly cooperate by exchanging compounds. Here, we examine this idea with an ecoevolutionary model where microbes make multiple secretions, which can be exchanged among genotypes. We show that cooperation between genotypes only evolves under specific demographic regimes characterized by intermediate genetic mixing. The key constraint on cooperative exchanges is a loss of autonomy: strains become reliant on complementary genotypes that may not be reliably encountered. Moreover, the form of cooperation that we observe arises through mutual exploitation that is related to cheating and "Black Queen" evolution for a single secretion. A major corollary is that the evolution of cooperative exchanges reduces community productivity relative to an autonomous strain that makes everything it needs. This prediction finds support in recent work from synthetic communities. Overall, our work suggests that natural selection will often limit cooperative exchanges in microbial communities and that, when exchanges do occur, they can be an inefficient solution to group living.