Biology subjects

Apidianakis, Y.

Publications and source records attributed to Apidianakis, Y..

4 recordsLinked to original sources

bioRxiv2019

Pseudomonas aeruginosa core metabolism exerts a widespread growth-independent control on virulence

Bacterial virulence may rely on secondary metabolism, but core metabolism genes are assumed to be necessary primarily for bacterial growth. To assess this assumption, we correlated the genome, the transcriptome and the pathogenicity of 30 fully sequenced Pseudomonas strains using two Drosophila and one mouse infection assay. In accordance with previous studies gene presence-absence does not explain differences in virulence among P. aeruginosa strains, but merely between P. aeruginosa and other Pseudomonas species. Similarly, classical gene expression analysis of highly vs. lowly pathogenic P. aeruginosa strains identifies many virulence factors, and only a few metabolism genes related to virulence. Nevertheless, assessing the virulence of 553 core metabolic and 95 random non-metabolic gene mutants of P. aeruginosa PA14, we found 16.5% of the core metabolic and 8.5% of the non-metabolic genes to be necessary for full virulence. Strikingly, 11.8% of the core metabolism genes exhibit defects in virulence that cannot be attributed to auxotrophy. The compromised in virulence metabolic gene mutants were mapped in multiple pathways and exhibited further defects in acute virulence phenotypes and in a mouse lung infection model. Functional transcriptomics re-analysis of core metabolism at the pathway level, reveals amino-acid, succinate, citramalate, and chorismate biosynthesis and beta-oxidation as important for full virulence and expression of these pathways indicative of virulence in various strains. Thus, P. aeruginosa virulence variation, which to this point remains unpredictably combinatorial at the gene level, can be dissected at the pathway level via combinatorial trancriptome and functional core metabolism analysis.

microbiology↗

bioRxiv2019

Intertwined trade-offs coordinate Drosophila midgut mitosis vs. endoreplication and host defense vs. dysplasia

Inflammatory signaling supports host defense against infection, not only through immune cells, but also via regeneration of damaged tissue. Heightened regeneration, nevertheless, predisposes for all types of cancer and thus a trade-off exists between regeneration capacity and long-term tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative inflammatory signaling in stem cell mitosis of the adult Drosophila midgut at the baseline and the infected state and its impact on intestinal host defense to infection and stem cell-mediated dysplasia. Through a quantitative genetics screen we find that stem cell mitosis is positively linked with the expression of eiger, Delta, upd3 and vein in the midgut, as well as with dysplasia and host defense, but negatively with enterocyte endoreplication. We provide evidence that intertwined trade-offs fine-tune midgut homeostasis, according to which stem cell mitosis through cyclin E in stem cells promotes the optimal host defense to infection, unless dysplasia ensues. However, cyclin E in enteroblasts promotes enterocyte endoreplication and counterbalances stem cell mitosis and dysplasia, providing an alternative but less efficient mechanism to support host defense.

cell biology↗

bioRxiv2019

Defining Escherichia coli as a health-promoting microbe against intestinal Pseudomonas aeruginosa

Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Taking a Kochs postulates approach in reverse to define health-promoting microbes we find that Escherichia coli naturally colonizes the gut of healthy mice, but it is depleted from the gut of antibiotic-treated mice, which become susceptible to intestinal colonization by Pseudomonas aeruginosa and concomitant mortality. Reintroduction of fecal bacteria and E. coli establishes a high titer of E. coli in the host intestine and increases defence against P. aeruginosa colonization and mortality. Moreover, diet is relevant in this process because high sugars or dietary fat favours E. coli fermentation to lactic acid and P. aeruginosa growth inhibition. To the contrary, low sugars allow P. aeruginosa to produce the oxidative agent pyocyanin that inhibits E. coli growth. Our results provide an explanation as to why P. aeruginosa doesnt commonly infect the human gut, despite being a formidable microbe in lung and wound infections.\n\nAuthor SummaryHere we interrogate the conundrum as to why Pseudomonas aeruginosa is not a clinical problem in the intestine as opposed to other tissues. P. aeruginosa interacts with Neisseria, Streptococcus, Staphylococcus and Actinomyces species found in the human lung. These are predominantly gram-positive bacteria that induce P. aeruginosa virulence. Moreover, peptidoglycan, which is abundant in gram-positive bacteria, can directly trigger the virulence of P. aeriginosa. We reasoned that P. aeruginosa might be benign in the human gut due to the inhibitory action of benign gram-negative intestinal bacteria, such as Escherichia coli. Therefore, we dissected the antagonism between E. coli and P. aeruginosa and the effect of a conventional, a fat-, a carbohydrate-and a protein-based diet in intestinal dysbiosis. Our findings support the notion that an unbalanced diet or antibiotics induces gut dysbiosis by the elimination of commensal E. coli, in addition to lactic acid bacteria, imposing a gut environment conducive to P. aeruginosa infection. Moreover, commensal E. coli provides an explanation as to why P. aeruginosa doesnt commonly infect the human gut, despite being a formidable microbe in lung and wound infections.

microbiology↗

bioRxiv2018

Unpredictable effects of the genetic background of transgenic lines in physiological quantitative traits

Most physiology, fitness and disease phenotypes are considered complex traits since they exhibit continuous variation in natural populations. The use of homozygous inbred strains allows the assessment of the impact of genetic composition on complex phenotypes. Nevertheless, to understand gene function, we often combine transgenic lines to assess the phenotype of interest in a heterozygous state. Here, using inbred wild-type Drosophila strains, we assessed the phenotypic variation of six physiology and fitness traits: female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. Indeed, we found continuous variation in all traits tested. To estimate the extent to which small genetic background differences affected these traits, we assessed the effects of commonly used Drosophila UAS-RNAi transgenic strains and their backcrossed isogenized counterparts in the same assays. We tested 20 non-isogenic strains (10 KK and 10 GD) from the Vienna Drosophila Resource Center and their isogenic counterparts without Gal4 induction and found that the different phenotypes were variably sensitive to the genetic background. For example, survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other phenotypes were affected in only 10-25% of the cases. We also observed that the genetic background affects Gal4 transgenes unpredictably. Thus, depending on the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.

genetics↗