Actinomycetes are a diverse family of filamentous bacteria that produce a plethora of natural products relevant for agriculture, biotechnology and medicine, including the majority of the antibiotics we use in the clinic. Rather than as free-living bacteria, many actinomycetes have evolved to live in symbiosis with among others plants, fungi, insects and sponges. As a common theme, these organisms profit from the natural products and enzymes produced by the actinomycetes, for example, for protection against pathogenic microbes, for growth promotion or for the degradation of complex natural polymers such as lignocellulose. At the same time, the actinomycetes benefit from the resources of the hosts they interact with. Evidence is accumulating that these interactions control the expression of biosynthetic gene clusters and have played a major role in the evolution of the high chemical diversity of actinomycete-produced secondary metabolites. Many of the biosynthetic gene clusters for antibiotics are poorly expressed under laboratory conditions, but they are likely expressed in response to host-specific demands. Here, we review the environmental triggers and cues that control natural product formation by actinomycetes and provide pointers as to how these insights may be harnessed for drug discovery.

A growing world population and an increasing demand for greater food production requires that crop losses caused by pests and diseases are dramatically reduced. Concurrently, sustainability targets mean that alternatives to chemical pesticides are becoming increasingly desirable. Bacteria in the plant root microbiome can protect their plant host against pests and pathogenic infection. In particular, Streptomyces species are well-known to produce a range of secondary metabolites that can inhibit the growth of phytopathogens. Streptomyces are abundant in soils and are also enriched in the root microbiomes of many different plant species, including those grown as economically and nutritionally valuable cereal crops. In this review we discuss the potential of Streptomyces to protect against some of the most damaging cereal crop diseases, particularly those caused by fungal pathogens. We also explore factors that may improve the efficacy of these strains as biocontrol agents in situ, as well as the possibility of exploiting plant mechanisms, such as root exudation, that enable the recruitment of microbial species from the soil to the root microbiome. We argue that a greater understanding of these mechanisms may enable the development of protective plant root microbiomes with a greater abundance of beneficial bacteria, such as Streptomyces species.

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defenses and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defenses such that colony collapse is unavoidable once Escovopsis infections escalate.

The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the Atta and Acromyrmex leafcutter ants, which harvest fresh leaves to feed their fungus. Acromyrmex and many other attines vertically transmit a mutualistic strain of Pseudonocardia and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus Escovopsis. Pseudonocardia mutualists associated with the attines Apterostigma dentigerum and Trachymyrmex cornetzi make novel cyclic depsipeptide compounds called gerumycins, while a mutualist strain isolated from derived Acromyrmex octospinosus makes an unusual polyene antifungal called nystatin P1. The novelty of these antimicrobials suggests there is merit in exploring secondary metabolites of Pseudonocardia on a genome-wide scale. Here, we report a genomic analysis of the Pseudonocardia phylotypes Ps1 and Ps2 that are consistently associated with Acromyrmex ants collected in Gamboa, Panama. These were previously distinguished solely on the basis of 16S rRNA gene sequencing but genome sequencing of five Ps1 and five Ps2 strains revealed that the phylotypes are distinct species and each encodes between 11 and 15 secondary metabolite biosynthetic gene clusters (BGCs). There are signature BGCs for Ps1 and Ps2 strains and some that are conserved in both. Ps1 strains all contain BGCs encoding nystatin P1-like antifungals, while the Ps2 strains encode novel nystatin-like molecules. Strains show variations in the arrangement of these BGCs that resemble those seen in gerumycin gene clusters. Genome analyses and invasion assays support our hypothesis that vertically transmitted Ps1 and Ps2 strains have antibacterial activity that could help shape the cuticular microbiome. Thus, our work defines the Pseudonocardia species associated with Acromyrmex ants and supports the hypothesis that Pseudonocardia species could provide a valuable source of new antimicrobials.

Streptomyces bacteria are ubiquitous in soils and are well-known for producing secondary metabolites, including antimicrobials. Increasingly, they are being isolated from plant roots and several studies have shown they are specifically recruited to the rhizosphere and the endosphere of the model plant Arabidopsis thaliana. Here we test the hypothesis that Streptomyces bacteria have a beneficial effect on A. thaliana growth and could potentially be used as plant probiotics. To do this, we selectively isolated streptomycetes from surface washed A. thaliana roots and generated high quality genome sequences for five strains which we named L2, M2, M3, N1 and N2. Re-infection of A. thaliana plants with L2, M2 and M3 significantly increased plant biomass individually and in combination whereas N1 and N2 had a negative effect on plant growth, likely due to their production of polyene natural products which can bind to phytosterols and reduce plant growth. N2 exhibits broad spectrum antimicrobial activity and makes filipin-like polyenes, including 14-hydroxyisochainin which inhibits the Take-all fungus, Gaeumannomyces graminis var. tritici. N2 antifungal activity as a whole was upregulated ∼2-fold in response to indole-3-acetic acid (IAA) suggesting a possible role during competition in the rhizosphere. Furthermore, coating wheat seeds with N2 spores protected wheat seedlings against Take-all disease. We conclude that at least some soil dwelling streptomycetes confer growth promoting benefits on A. thaliana while others might be exploited to protect crops against disease. Importance. We must reduce reliance on agrochemicals and there is increasing interest in using bacterial strains to promote plant growth and protect against disease. Our study follows up reports that Arabidopsis thaliana specifically recruits Streptomyces bacteria to its roots. We test the hypothesis that they offer benefits to their A. thaliana hosts and that strains isolated from these plants might be used as probiotics. We isolated Streptomyces strains from A. thaliana roots and genome sequenced five phylogenetically distinct strains. Genome mining and bioassays indicated that all five have plant growth promoting properties, including production of IAA, siderophores and ACC deaminase. Three strains significantly increased A. thaliana growth in vitro and in combination in soil. Another produces potent filipin-like antifungals and protected germinating wheat seeds against the fungal pathogen Gaeumannomyces graminis var. tritici (wheat Take-all fungus). We conclude that introducing Streptomyces strains into the root microbiome provides significant benefits to plants.

Background The vertebrate gut microbiome (GM) can vary substantially across individuals within the same natural population. Although there is evidence linking the GM to health in captive animals, very little is known about the consequences of GM variation for host fitness in the wild. Here, we explore the relationship between faecal microbiome diversity, body condition, and survival using data from the long-term study of a discrete natural population of the Seychelles warbler (Acrocephalus sechellensis) on Cousin Island. To our knowledge, this is the first time that GM differences associated with survival have been fully characterised for a natural vertebrate species, across multiple age groups and breeding seasons. Results We identified substantial variation in GM community structure among sampled individuals, which was partially explained by breeding season (5% of the variance), and host age class (up to 1% of the variance). We also identified significant differences in GM community membership between adult birds that survived, versus those that had died by the following breeding season. Individuals that died carried increased abundances of taxa that are known to be opportunistic pathogens, including several ASVs in the genus Mycobacterium. However, there was no association between GM alpha diversity (the diversity of bacterial taxa within a sample) and survival to the next breeding season, or with individual body condition. Additionally, we found no association between GM community membership and individual body condition. Conclusions These results demonstrate that components of the vertebrate GM can be associated with host fitness in the wild. However, further research is needed to establish whether changes in bacterial abundance contribute to, or are only correlated with, differential survival; this will add to our understanding of the importance of the GM in the evolution of host species living in natural populations.

Background The gut microbiome (GM) can influence many biological processes in the host, impacting its health and survival, but the GM can also be influenced by the host’s traits. In vertebrates, Major Histocompatibility Complex (MHC) genes play a pivotal role in combatting pathogens and are thought to shape the host’s GM. Despite this—and the documented importance of both GM and MHC variation to individual fitness—few studies have investigated the association between the GM and MHC in the wild. Results We characterised MHC class I (MHC-I), MHC class II (MHC-II) and GM variation in individuals within a natural population of the Seychelles warbler (Acrocephalus sechellensis). We determined how the diversity and composition of the GM varied with MHC characteristics, in addition to environmental factors and other host traits. Our results show that the presence of specific MHC alleles, but not MHC diversity, influences both the diversity and composition of the GM in this population. MHC-I alleles, rather than MHC-II alleles, had the greatest impact on the GM. GM diversity was negatively associated with the presence of three MHC-I alleles (Ase-ua3, Ase-ua4, Ase-ua5), and one MHC-II allele (Ase-dab4), while changes in GM composition were associated with the presence of four different MHC-I alleles (Ase-ua1, Ase-ua7, Ase-ua10, Ase-ua11). There were no associations between GM diversity and TLR3 genotype, but GM diversity was positively correlated with genome-wide heterozygosity and varied with host age and field period. Conclusions These results suggest that components of the host’s immune system play a role in shaping the GM of wild animals. Host genotype—specifically MHC-I and to a lesser degree MHC-II variation—can modulate the GM, although whether this occurs directly, or indirectly through effects on host health, is unclear. Importantly, if immune genes can regulate host health through modulation of the microbiome, then it is plausible that the microbiome could also influence selection on immune genes. As such, host–microbiome coevolution may play a role in maintaining functional immunogenetic variation within natural vertebrate populations.

Understanding the mechanisms that promote the assembly and maintenance of host-beneficial microbiomes is an open problem. Empirical evidence supports the idea that animal and plant hosts can combine ‘private resources’ with the ecological phenomenon known as ‘community bistability’ to favour some microbial strains over others. We briefly review evidence showing that hosts can: (i) protect the growth of beneficial strains in an isolated habitat, (ii) use antibiotics to suppress non-beneficial, competitor strains, and (iii) provide resources that only beneficial strains are able to translate into an increased rate of growth, reproduction, or antibiotic production. We then demonstrate in a spatially explicit, individual-based model that these three mechanisms act similarly by selectively promoting the initial proliferation of preferred strains, that is, by acting as a private resource. The faster early growth of preferred strains, combined with the phenomenon of ‘community bistability,’ allows those strains to continue to dominate the microbiome even after the private resource is withdrawn or made public. This is because after a beneficial colony reaches a sufficiently large size, it can resist invasion by parasites without further private support from the host. We further explicitly model localized microbial interactions and diffusion dynamics, and we show that an intermediate level of antibiotic diffusion is the most efficient mechanism in promoting preferred strains and that there is a wide range of parameters under which hosts can promote the assembly of a self-sustaining defensive microbiome. This in turn supports the idea that hosts readily evolve to promote host-beneficial defensive microbiomes.