Cluff, A. | Search bioRxiv

bioRxiv2024

Environment and diet shape the geography-specific Drosophila melanogaster microbiota composition

Geographic and environmental variation in the animal microbiota can be directly linked to the evolution and wild fitness of their hosts but often appears to be disordered. Here, we sought to better understand patterns that underlie wild variation in the microbiota composition of Drosophila melanogaster. First, environmental temperature predicted geographic variation in fly microbial communities better than latitude did. The microbiota also differed between wild flies and their diets, supporting previous conclusions that the fly microbiota is not merely a reflection of diet. Flies feeding on different diets varied significantly in their microbiota composition, and flies sampled from individual apples were exceptionally depauperate for the Lactic Acid Bacteria (LAB), a major bacterial group in wild and laboratory flies. However, flies bore significantly more LAB when sampled from other fruits or compost piles. Follow-up analyses revealed that LAB abundance in the flies uniquely responds to fruit decomposition, whereas other microbiota members better indicate temporal seasonal progression. Finally, we show that diet-dependent variation in the fly microbiota is associated with phenotypic differentiation of fly lines collected in a single orchard. These last findings link covariation between the flies dietary history, microbiota composition, and genetic variation across relatively small (single-orchard) landscapes, reinforcing the critical role that environment-dependent variation in microbiota composition can play in local adaptation and genomic differentiation of a model animal host. SIGNIFICANCE STATEMENTThe microbial communities of animals influence their hosts evolution and wild fitness, but it is hard to predict and explain how the microbiota varies in wild animals. Here, we describe that the microbiota composition of wild Drosophila melanogaster can be ordered by temperature, humidity, geographic distance, diet decomposition, and diet type. We show how these determinants of microbiota variation can help explain lactic acid bacteria (LAB) abundance in the flies, including the rarity of LAB in some previous studies. Finally, we show that wild fly phenotypes segregate with the flies diet and microbiota composition, illuminating links between the microbiota and host evolution. Together, these findings help explain how variation in microbiota compositions can shape an animals life history.

microbiology↗

bioRxiv2023

Human Rhinoviruses: a novel class of oncolytic virus

While continuing to develop new and improved OVs, researchers have been vigilant in optimizing their ability to safely infect, replicate, and induce an immune response within tumors. There are currently two crucial limitations in OV development, however: modification of viruses often negatively impact their ability to infect, and induction of strong immune responses also promotes rapid viral clearance. In this study, we investigate wild-type HRVs as a novel class of OV. Multiple HRV serotypes were propagated in human melanoma cell lines to produce highly oncolytic populations of virus. A large panel of cancer types were infected, with cytotoxicity evaluated using flow cytometry and real time live imaging. Pro-inflammatory signaling was assessed by cytokine multiplexing. Tumor responses to HRV were assessed in human xenograft and in syngeneic, immune-competent mouse tumor models. We find that HRVs are capable of infecting and killing a wide variety of human cancer cell lines in vitro and in vivo, inducing pro-inflammatory responses and, ultimately, tumor regression. We propose that the natural safety profile of these viruses, coupled with their anti-tumor efficacy and multivalent potential seen in our preclinical model systems, make HRVs ideal candidates for development as oncolytic viruses for clinical testing. Simple SummaryThe idea of utilizing viruses to combat cancer has been around for over a century, yet in practice has seen relatively modest therapeutic success following decades of strategic design to improve safety, efficacy, and tumor selectivity. Engagement of an immune response is critical to have lasting tumor regression upon treatment, but many patients are unable to mount a sufficient response to standard-of-care immunotherapy alone. Oncolytic viruses (OVs) have been shown to synergize with such therapies to accomplish this goal to varying degrees. The purpose of this study is to investigate human rhinoviruses (HRVs) to establish their efficacy as a novel class of anti-cancer agents. We aim to use HRVs to promote longer lasting and more effective immune responses to tumors by fostering viral persistence and immune evasion, in addition to developing multivalent treatment strategies that enhance tumor regression by preventing tumor escape from viral infection.

immunology↗