Research in our lab can be grouped into four areas:

1. Understanding how chemical warfare drives evolution using Acromyrmex echinatior leafcutter ants as a model. Acromyrmex leafcutter ants form a tripartite, mutually beneficial symbiosis (mutualism) with the food fungus Leucoagaricus gongylophorus and a strain of Pseudonocardia bacteria. The bacteria make antibiotics which the ants use to defend their food fungus against a fourth symbiont, co-evolved parasitic fungi in the genus Escovopsis that feed off the Leucoagaricus (Figure 1). This well studied system offers prime opportunities for studying microbiome formation, mutualisms and arms races between symbionts. (e.g. Barke et al 2010; Seipke et al 2011; Holmes et al 2016; Heine et al 2018, submitted).

Figure 1. Left. Summary of interactions between the symbionts in the leafcutter ant system (green is positive and red is negative). Right. One of our captive leafcutter ant colonies.

2. Exploring unusual environments and ecological niches including plant roots and fungus growing ant nests for new antibiotics. The symbiotic actnomycete strains associated with plants and animals encode numereous secondary metabolites but most of these are not produced when we grow the bactria in the lab. We are using CRISPR/Cas9 based genome engineering to activate production of novel molecules from these strains and then testing them for bioactivity. We recently discovered a new group of antibiotics we called formicamycins from an ant-associated strain called Streptomyces formicae (Qin et al 2017; Holmes et al 2018).

Figure 2. Streptomyces formicae is a new species isolated from Tetraponera plant ants. We sequenced the genome and identified 45 biosynthetic gene clusters for secondary metabolites. It makes potent antibacterials and antifungals under lab conditions, including a novel group of antibiotics called formicamycins that are potent against MRSA and have a high barrier to resistance

3. Understanding the recruitment and role of Streptomyces bacteria in plant roots. The roots of some plants contain much higher numbers of Streptomyces bacteria than the surrounding soil, i.e. they are enriched and this suggests the plants specifically recruit them from soil. We are using the model plant Arabidopsis thaliana and the crop plant Triticum aestivum (bread wheat) to understand how plants recruit these bacteria and what benefits they offer to their host plants.

Figure 3. Left. Heat map where red is high and yellow is low. This shows that Streptomyces species (black arrow) are highly enriched inside A. thaliana plant roots relative to the woil or rhizpsphere (the soil touching the roots). Right. A. thaliana plants grown on sterile agar without (control) or with different Streptomyces species, all of which are attracted to and grow onto the roots of the plants.

4. Analysing two-component signal transduction pathways to understand how they regulate antibiotic production in Streptomyces species. We are undertaking a systems level analysis of two-component signalling in Streptomyces species using S. venezuelae as a model. Two-component systems allow bacteria to rapidly sense and repsond to their environment and we are identifying systems which control the production of secondary metabolites and exploiting this knowledge to induce the over production of antibiotics. (Som et al 2017a; 2017b).

Figure 4. Left. ChIP-seq against the two-component system regulator MtrA throughout the life cycle of S. venezuelae shows that it binds key cell division targets including the origin of DNA replication, oriC, and many of the secondary metabolite gene clusters (not shown). Right. Disruption of the MtrAB two component system uncouples antibiotic production from sporulation such that antibiotics are produced constitutively and at a high level.

Updated 23rd February 2018