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Intestinal microbes, whether resident or transient, influence the physiology of their hosts, altering both the chemical and the physical characteristics of the gut. An example of the latter is the human pathogenVibrio cholerae’sability to induce strong mechanical contractions, discovered in zebrafish. The underlying mechanism has remained unknown, but the phenomenon requires the actin crosslinking domain (ACD) ofVibrio’s type VI secretion system (T6SS), a multicomponent protein syringe that pierces adjacent cells and delivers toxins. By using a zebrafish-nativeVibrioand imaging-based assays of host intestinal mechanics and immune responses, we find evidence that macrophages mediate the connection between the T6SS ACD and intestinal activity. Inoculation withVibriogives rise to strong, ACD-dependent, gut contractions whose magnitude resembles those resulting from genetic depletion of macrophages.Vibrioalso induces tissue damage and macrophage activation, both ACD-dependent, recruiting macrophages to the site of tissue damage and away from their unperturbed positions near enteric neurons that line the midgut and regulate intestinal motility. Given known crosstalk between macrophages and enteric neurons, our observations suggest that macrophage redistribution forms a key link betweenVibrioactivity and intestinal motility. In addition to illuminating host-directed actions of the widespread T6SS protein apparatus, our findings highlight how localized bacteria-induced injury can reshape neuro-immune cellular dynamics to impact whole-organ physiology. IMPORTANCEGut microbes, whether beneficial, harmful, or neutral, can have dramatic effects on host activities. The human pathogenVibrio choleraecan induce strong intestinal contractions, though how this is achieved has remained a mystery. Using a zebrafish-nativeVibrioand live imaging of larval fish, we find evidence that immune cells mediate the connection between bacteria and host mechanics. A piece ofVibrio’s type VI secretion system, a syringe-like apparatus that stabs cellular targets, induces localized tissue damage, activating macrophages and drawing them from their normal residence near neurons, whose stimulation of gut contractions they dampen, to the damage site. Our observations reveal a mechanism in which cellular rearrangements, rather than bespoke biochemical signaling, drives a dynamic neuro-immune response to bacterial activity. 

ABSTRACT Fungal pathogens, among other stressors, negatively impact the productivity and population size of honey bees, one of our most important pollinators (1, 2), in particular their brood (larvae and pupae) (3, 4). Understanding the factors that influence disease incidence and prevalence in brood may help us improve colony health and productivity. Here, we examined the capacity of a honey bee-associated bacterium, Bombella apis , to suppress the growth of fungal pathogens and ultimately protect bee brood from infection. Our results showed that strains of B. apis inhibit the growth of two insect fungal pathogens, Beauveria bassiana and Aspergillus flavus , in vitro . This phenotype was recapitulated in vivo ; bee broods supplemented with B. apis were significantly less likely to be infected by A. flavus . Additionally, the presence of B. apis reduced sporulation of A. flavus in the few bees that were infected. Analyses of biosynthetic gene clusters across B. apis strains suggest antifungal candidates, including a type 1 polyketide, terpene, and aryl polyene. Secreted metabolites from B. apis alone were sufficient to suppress fungal growth, supporting the hypothesis that fungal inhibition is mediated by an antifungal metabolite. Together, these data suggest that B. apis can suppress fungal infections in bee brood via secretion of an antifungal metabolite. IMPORTANCE Fungi can play critical roles in host microbiomes (5–7), yet bacterial-fungal interactions are understudied. For insects, fungi are the leading cause of disease (5, 8). In particular, populations of the European honey bee ( Apis mellifera ), an agriculturally and economically critical species, have declined in part due to fungal pathogens. The presence and prevalence of fungal pathogens in honey bees have far-reaching consequences, endangering other species and threatening food security (1, 2, 9). Our research highlights how a bacterial symbiont protects bee brood from fungal infection. Further mechanistic work could lead to the development of new antifungal treatments.