Biology subjects

Paulo, T. F.

Publications and source records attributed to Paulo, T. F..

3 recordsLinked to original sources

bioRxiv2025

A conserved, immune-regulated peritrophin promotes Vibrio cholerae colonization of the arthropod intestine

Vibrio cholerae is a human diarrheal pathogen and an estuarine organism that associates with both terrestrial and aquatic arthropods. Using the model terrestrial arthropod Drosophila melanogaster, we previously showed that V. cholerae forms a multi-layered bacterial structure called a biofilm in the arthropod intestine and activates the arthropod intestinal innate immune response. Here we show that activation of the immune response in enterocytes decreases V. cholerae colonization of the arthropod intestine, while activation of the immune response in enteroendocrine cells that express the enteroendocrine peptide tachykinin (Tk) promotes V. cholerae colonization. To uncover the basis of this observation, we measured the impact of TkRNAi on intestinal gene expression by RNA-seq analysis. In addition to increasing expression of antimicrobial peptides and lipases, Tk activated the expression of chitinases and chitin-binding proteins. These proteins interact with chitin fibrils in the peritrophic matrix (PM), a protective coating that overlies the arthropod intestinal epithelium. One of these Tk-activated PM components, the small, secreted chitin-binding protein Peritrophin 15a (Peri-15a), is essential for robust V. cholerae colonization of the gut. Homologs of Peri-15a are widespread in both terrestrial and aquatic organisms including marine non-biting midges, marine copepods, rotifers, and cyanobacteria. We propose that Peri-15a and its homologs, found in the intestines of diverse arthropods, either serves as a receptor or reveals a PM epitope that promotes V. cholerae attachment to the intestinal surface. Therefore, activation of the enteroendocrine cell intestinal innate immune response by V. cholerae may, in fact, represent a colonization strategy.

microbiology↗

bioRxiv2025

Pathogen-Induced Damage in Drosophila: Uncoupling Disease Tolerance from Resistance

Immune response against infections can be divided into mechanisms of resistance that ensure active pathogen elimination, and mechanisms of disease tolerance, which include processes that return the host to physiological homeostasis without involving direct pathogen control. Studies on host immune responses to infection have mostly targeted mechanisms of resistance, and consequently, these are now well-described in both vertebrates and invertebrates. By comparison, the mechanistic basis of disease tolerance is less well understood. This is in part because both processes interact and can be difficult to separate under an infection scenario. Using the highly tractable insect model Drosophila melanogaster exposed to its natural entomopathogen, Pseudomonas entomophila, we aimed to tease apart mechanisms of disease tolerance from those of resistance. To this aim, we reasoned that oral exposure to heat-killed entomopathogenic bacteria should require disease tolerance without relying on resistance. Using this method, we observe that oral exposure to heat-killed P. entomophila causes mortality and reduced fecundity in D. melanogaster. We confirm that this reduction in fitness-related traits depends on the duration of the exposure, is sexually dimorphic, and is dependent on the virulence of the bacterium. We also found the microbiota to play a role, with its presence exacerbating the deleterious effect on host survival. This experimental framework, which may be extended to other systems, can be instrumental towards an understanding of the molecular, genetic, and physiological basis of disease tolerance and its interactions with resistance mechanisms.

immunology↗

bioRxiv2023

Adaptation to oral infection in D. melanogaster through evolution of both resistance and disease tolerance mechanisms

Pathogens exert strong selection on hosts, that evolve and deploy different defensive strategies, namely minimizing pathogen exposure (avoidance), directly promoting pathogen elimination (resistance), and/or managing the deleterious effects of illness (disease tolerance). However, how the response to pathogens partitions across these processes has never been directly assessed in a single system, let alone in the context of known adaptive trajectories under controlled selection regimes. Here, an experimental evolution system composed of D. melanogaster and its natural pathogen P. entomophila is used to independently assess the role of behavioural traits, and of resistance and disease tolerance mechanisms on host evolution. We compare one replicate of a population adapted to oral infection with P. entomophila (BactOral) to a replicate of its control population to find no evidence for behavioural change but measurable differences in both resistance and disease tolerance. In BactOral, we identify a relative decrease in bacterial loads correlated with an increase in gut production of specific AMPs, but no differences in bacterial intake, in gut cell renewal rate, or in the rate of bacterial defecation, pointing to a strengthening in resistance. Additionally, we posit that disease tolerance also contributes to the adaptive response of the BactOral population through a tighter control of its immune response and of the deleterious effects of exposure. This study reveals a genetically complex and mechanistically multi-layered response, possibly reflecting the structure of adaptation to infection in natural populations.

evolutionary biology↗