Natural Variation in Physicochemical Profiles and Bacterial Communities Associated with Aedes aegypti Breeding Sites and Larvae on Guadeloupe and French Guiana.

Aedes aegypti develop in aquatic habitats in which mosquito larvae are exposed to physicochemical elements and microorganisms that may influence their life cycle and their ability to transmit arboviruses. Little is known about the natural bacterial communities associated with A. aegypti or their relation to the biotic and abiotic characteristics of their aquatic habitats. We characterized the physicochemical properties and bacterial microbiota of A. aegypti breeding sites and larvae on Guadeloupe and in French Guiana. In addition, we explored whether geographic location, the type of breeding site and physicochemical parameters influenced the microbiota associated with this mosquito species. We used large-scale 16S rRNA gene sequencing of 160 breeding sites and 147 pools of A. aegypti larvae and recorded 12 physicochemical parameters at the sampled breeding sites. Ordination plots and multiple linear regression were used to assess the influence of environmental factors on the bacterial microbiota of water and larvae. We found territory-specific differences in physicochemical properties (dissolved oxygen, conductivity) and the composition of bacterial communities in A. aegypti breeding sites that influenced the relative abundance of several bacteria genera (e.g., Methylobacterium, Roseoccocus) on the corresponding larvae. A significant fraction of the bacterial communities identified on larvae, dominated by Herbiconiux and Microvirga genera, were consistently enriched in mosquitoes regardless the location. In conclusion, territory-specific differences observed in the biotic and abiotic properties of A. aegypti breeding sites raise concern about the impact of these changes on pathogen transmission by different A. aegypti populations.

Colorectal cancer cells respond differentially to autophagy inhibition in vivo.

Autophagy has both tumor-promoting and -suppressing effects in cancer, including colorectal cancer (CRC), with transformed cells often exhibiting high autophagic flux. In established tumors, autophagy inhibition can lead to opposite responses resulting in either tumor cell death or hyperproliferation. The functional mechanisms underlying these differences are poorly understood. The present study aimed to investigate the relationship between the autophagic capacities of CRC cells and their sensitivities to autophagy inhibition. All studied CRC cell lines showed high basal autophagic flux. However, only HCT116 and Caco-2/15 cells displayed regulated autophagic flux upon starvation. Knockdown of ATG5 (which disrupts autophagosome elongation) or RAB21 (which decreases autophagosome/lysosome fusion) had little effect on CRC cell proliferation in vitro. Nonetheless, inhibition of autophagy in vivo had a substantial cell line-dependent impact on tumor growth, with some cells displaying decreased (HCT116 and Caco-2/15) or increased (SW480 and LoVo) proliferation. RNA sequencing and Western blot analyses in hyperproliferative SW480 tumors revealed that the mTORC2 and AKT pathways were hyperactivated following autophagy impairment. Inhibition of either mTOR or AKT activities rescued the observed hyperproliferation in autophagy-inhibited SW480 and reduced tumor growth. These results highlight that autophagy inhibition can lead, in specific cellular contexts, to compensatory mechanisms promoting tumor growth.