Host-derived organic acids enable gut colonization of the honey bee symbiont Snodgrassella alvi.

Diverse bacteria can colonize the animal gut using dietary nutrients or by engaging in microbial crossfeeding interactions. Less is known about the role of host-derived nutrients in enabling gut bacterial colonization. Here we examined metabolic interactions within the evolutionary ancient symbiosis between the honey bee (Apis mellifera) and the core gut microbiota member Snodgrassella alvi. This betaproteobacterium is incapable of metabolizing saccharides, yet colonizes the honey bee gut in the presence of a sugar-only diet. Using comparative metabolomics, 13C-tracers and nanoscale secondary ion mass spectrometry (NanoSIMS), we show in vivo that S. alvi grows 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. alvi also modulates tryptophan metabolism in the gut by converting kynurenine to anthranilate. These results suggest that S. alvi is adapted to a specific metabolic niche in the honey bee gut that depends on host-derived nutritional resources.

Integration host factor regulates colonization factors in the bee gut symbiont Frischella perrara.

Bacteria colonize specific niches in the animal gut. However, the genetic basis of these associations is often unclear. The proteobacterium Frischella perrara is a widely distributed gut symbiont of honey bees. It colonizes a specific niche in the hindgut and causes a characteristic melanization response. Genetic determinants required for the establishment of this association, or its relevance for the host, are unknown. Here, we independently isolated three point mutations in genes encoding the DNA-binding protein integration host factor (IHF) in F. perrara. These mutants abolished the production of an aryl polyene metabolite causing the yellow colony morphotype of F. perrara. Inoculation of microbiota-free bees with one of the mutants drastically decreased gut colonization of F. perrara. Using RNAseq, we found that IHF affects the expression of potential colonization factors, including genes for adhesion (type 4 pili), interbacterial competition (type 6 secretion systems), and secondary metabolite production (colibactin and aryl polyene biosynthesis). Gene deletions of these components revealed different colonization defects depending on the presence of other bee gut bacteria. Interestingly, one of the T6SS mutants did not induce the scab phenotype anymore despite colonizing at high levels, suggesting an unexpected role in bacteria-host interaction. IHF is conserved across many bacteria and may also regulate host colonization in other animal symbionts.

Deep Divergence and Genomic Diversification of Gut Symbionts of Neotropical Stingless Bees.

Social bees harbor conserved gut microbiotas that may have been acquired in a common ancestor of social bees and subsequently codiversified with their hosts. However, most of this knowledge is based on studies on the gut microbiotas of honey bees and bumblebees. Much less is known about the gut microbiotas of the third and most diverse group of social bees, the stingless bees. Specifically, the absence of genomic data from their microbiotas 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 bumblebee 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 codiversification but included host switches and independent symbiont gain and losses. Finally, as reported for the honey bee and bumblebee microbiotas, we found 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. IMPORTANCE 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. Few bacteria have been cultured from the gut of stingless bees, which has prevented characterization of their genomic diversity and functional potential. Here, we established cultures of major members of the gut microbiotas of six stingless bee species and sequenced their genomes. We found that most stingless bee isolates belong to novel bacterial species distantly related to those found in honey bees and bumblebees and encoding similar functional capabilities. Our study offers a new perspective on the evolution of the social bee gut microbiota and presents a basis for characterizing the symbiotic relationships between gut bacteria and stingless bees.

Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?

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.