Agricultural industry uses pesticides to optimize food production for the growing human population. A major issue for crops is fungal phytopathogens, which are treated mainly with azole fungicides. Azoles are also the main medical treatment in the management of Aspergillus diseases caused by ubiquitous fungi, such as Aspergillus fumigatus. However, epidemiological research demonstrated an increasing prevalence of azole-resistant strains in A. fumigatus. The main resistance mechanism is a combination of alterations in the gene cyp51A (TR34/L98H). Surprisingly, this mutation is not only found in patients receiving long-term azole therapy for chronic aspergillosis but also in azole naïve patients. This suggests an environmental route of resistance through the exposure of azole fungicides in agriculture. In this review, we report data from several studies that strongly suggest that agricultural azoles are responsible for medical treatment failure in azole-naïve patients in clinical settings.

Stingless bees are the most diverse group of the corbiculate bees and represent important pollinator species throughout the tropics and subtropics. They harbor specialized microbial communities in their gut that are related to those found in honey bees and bumblebees and that are likely important for bee health.

Social bees harbor conserved gut microbiota that may have been acquired in a common ancestor of social bees and subsequently co-diversified with their hosts. However, most of this knowledge is based on studies on the gut microbiota of honey bees and bumble bees. Much less is known about the gut microbiota of the third and most diverse group of social bees, the stingless bees. Specifically, the absence of genomic data from their microbiota presents an important knowledge gap in understanding the evolution and functional diversity of the social bee microbiota. Here we combined community profiling with culturing and genome sequencing of gut bacteria from six neotropical stingless bee species from Brazil. Phylogenomic analyses show that most stingless bee gut isolates form deep-branching sister clades of core members of the honey bee and bumble bee gut microbiota with conserved functional capabilities, confirming the common ancestry and ecology of their microbiota. However, our bacterial phylogenies were not congruent with those of the host indicating that the evolution of the social bee gut microbiota was not driven by strict co-diversification, but included host switches and independent symbiont gain and losses. Finally, as reported for the honey bee and bumble bee microbiota, we find substantial genomic divergence among strains of stingless bee gut bacteria suggesting adaptation to different host species and glycan niches. Our study offers first insights into the genomic diversity of the stingless bee microbiota, and highlights the need for broader samplings to understand the evolution of the social bee gut microbiota.

Nutrients from the host diet and microbial cross-feeding allow diverse bacteria to colonize the animal gut. Less is known about the role of host-derived nutrients in enabling gut bacterial colonization. We examined metabolic interactions within the evolutionary ancient symbiosis between the honey bee (Apis mellifera) and the core gut microbiota memberSnodgrassella alvi. This Betaproteobacteria is incapable of metabolizing saccharides, yet colonizes the honey bee gut in the presence of only a sugar diet. Using comparative metabolomics,13C tracers, and Nanoscale secondary ion mass spectrometry (NanoSIMS), we showin vivothatS. alvigrows on host-derived organic acids, including citrate, glycerate and 3-hydroxy-3-methylglutarate which are actively secreted by the host into the gut lumen.S. alviadditionally modulates tryptophan metabolism in the gut, primarily by converting kynurenine to anthranilate. These results suggest thatSnodgrassellais adapted to a specific metabolic niche in the gut that depends on host-derived nutritional resources.

Bacteria colonize specific niches in the animal gut. However, the genetic basis of these associations is often unclear. The protobacterium Frischella perrara colonizes the hindgut of honey bees, where it causes a characteristic immune response leading to the formation of the scab phenotype. Genetic determinants required for the establishment of this specific association are unknown. Here, we isolated three point mutations in the genes encoding the DNA-binding protein integration host factor (IHF). All three mutants formed larger colonies than the wild type in vitro and did not produce an aryl polyene metabolite, which confers a yellow color to F. perrara colonies. Inoculation of microbiota-free bees with one of the mutants drastically decreased gut colonization of F. perrara and abolished scab development. Using RNAseq we find that IHF affects the expression of potential colonization factors, including a colibactin biosynthetic gene cluster, two Type 6 secretion systems, pili genes, and the aryl polyene biosynthesis pathway. Gene deletions of these components revealed different colonization defects. While some mutants were abolished in their capacity to colonize the gut, others colonized but did not trigger the scab phenotype. IHF is conserved across many bacteria and may thus regulate host colonization also in other animal symbionts.