Yiorgos Apidianakis

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Verified

Yiorgos verified their affiliation via an institutional email.

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• Associate Professor of Genetics
• Professor (Associate) at University of Cyprus

Although pathogenic bacteria are suspected contributors to colorectal cancer progression, cancer-promoting bacteria and their mode of action remain largely unknown. Here we report that sustained infection with the human intestinal colonizer Pseudomonas aeruginosa synergizes with the Ras1V12 oncogene to induce basal invasion and dissemination of hin...

Bacteria contaminate insects and secrete metabolites that may affect insect behaviour and potentially fitness through unknown mechanisms. Here we show that the 'grape-like' odorant 2-aminoacetophenone (2AA), secreted by Pseudomonas aeruginosa (a ubiquitous opportunistic human pathogen), facilitates attraction to food for several fly species includi...

Intestinal inflammation is widely recognized as a pivotal player in health and disease. Defined cytologically as the infiltration of leukocytes in the lamina propria layer of the intestine, it can damage the epithelium and, on a chronic basis, induce inflammatory bowel disease and potentially cancer. The current view thus dictates that blood cell i...

Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult...

This is a bold, thought-provoking exploration of the gaps in our understanding of the ethical, philosophical, and political ramifications of our genetics and how they are shaped by our environments. Disentangling humans synthesizes life and social sciences, and the humanities, into a philosophical understanding of humans in terms of wellbeing, soc...

Oil bioremediation may be achievable via Pseudomonas spp. leading to low-cost biosurfactant (BSF) production, but the environmental impact is unclear. Here, we studied P. aeruginosa PA14 and PAO1; P. putida mt-2 and F1; and P. citronellolis 620C, P3B5, and SJTE-3, for their ability to degrade oily wastewater (OW), produce BSFs, and impact the model...

Cancer cell invasion and subsequent metastasis account for most cancer related deaths. However, despite recent progress, there is a need to understand how the main pathways involved in oncogenic cell invasion and metastasis amalgamate into multifunctional networks. Using functional transcriptomic analysis of Drosophila Ras oncogenic hindgut enteroc...

Background The gut microbiome influences the host immune system, cancer development and progression, as well as the response to immunotherapy during cancer treatment. Here, we analyse the composition of the gut bacteriome in metastatic Non‐Small Cell Lung Cancer (NSCLC) patients receiving Pembrolizumab immunotherapy within a prospective maintenance...

Stem cell accumulation and mutation-derived tumors are two hallmarks of Drosophila midgut aging. They imply a decline in stem cell signaling homeostasis late in life and a robust homeostasis in young adults. Contrary to this, we find spontaneously developing stem-like cells that vary in size and ploidy, have a stem-enteroblast mixed identity, achie...

Colorectal cancer remains a major global health concern. Colonoscopy, the gold-standard colorectal cancer diagnostic, relies on the visual detection of lesions and necessitates invasive biopsies for confirmation. Alternative diagnostic methods, based on nanomedicine, can facilitate early detection of malignancies. Here, we examine the uptake of sur...

Pseudomonas aeruginosa requires a significant breach in the host defense to cause an infection. While its virulence factors are well studied, its tropism cannot be explained only by studying its interaction with the host. Why are P. aeruginosa infections so rare in the intestine compared with the lung and skin? There is not enough evidence to claim...

Microbiota and the metabolites they produce within the large intestine interact with the host epithelia under the influence of a range of host-derived metabolic, immune, and homeostatic factors. This complex host–microbe interaction affects intestinal tumorigenesis, but established microbial or metabolite profiles predicting colorectal cancer (CRC)...

Microbiota and the metabolites they produce within the large intestine interact with the host epithelia under the influence of a range of host-derived metabolic, immune, and homeostatic factors. This complex host-microbe interaction affects intestinal tumorigenesis but established microbial or metabolite profiles predicting colorectal cancer (CRC)...

A trade-off hypothesis pertains to the biased allocation of limited resources between two of the most important fitness traits, reproduction and survival to infection. This quid pro quo manifests itself within animals prioritizing their energetic needs according to genetic circuits balancing metabolism, germline activity and immune response. Key ev...

Peptide hormones control Drosophila gut motility, but the intestinal stimuli and the gene networks coordinating this trait remain poorly defined. Here, we customized an assay to quantify female Drosophila defecation rate as a proxy of intestinal motility. We found that bacterial infection with the human opportunistic bacterial pathogen Pseudomonas...

Human history is inextricably linked to the introduction of desirable heritable traits in plants and animals. Selective breeding (SB) predates our historical period and has been practiced since the advent of agriculture and farming more than ten thousand years ago. Since the 1970s, methods of direct plant and animal genome manipulation are constant...

Colorectal cancer (CRC) is one of the most prevalent cancers affecting humans, with a complex genetic and environmental aetiology. Unlike cancers with known environmental, heritable, or sex-linked causes, sporadic CRC is hard to foresee and has no molecular biomarkers of risk in clinical use. One in twenty CRC cases presents with an established her...

Microbiota may alter a pathogen’s virulence potential at polymicrobial infection sites. Here, we developed a multi-modal Drosophila assay, amenable to the assessment of human bacterial interactions using fly survival or midgut regeneration as a readout, under normoxia or mild hypoxia. Deploying a matrix of 12 by 33 one-to-one Drosophila co-infectio...

Clostridioides difficile infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen C. difficile. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commen...

Accelerating growth and global expansion of antimicrobial resistance has deepened the need for discovery of novel antimicrobial agents. Antimicrobial peptides have clear advantages over conventional antibiotics which include slower emergence of resistance, broad-spectrum antibiofilm activity, and the ability to favourably modulate the host immune r...

To assess the role of core metabolism genes in bacterial virulence - independently of their effect on growth - we correlated the genome, the transcriptome and the pathogenicity in flies and mice of 30 fully sequenced Pseudomonas strains. Gene presence correlates robustly with pathogenicity differences among all Pseudomonas species, but not among th...

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 prev...

Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Although lactobacilli and bifidobacteria produce beneficial lactic and short-chain fatty acids in the mammalian gut, the significance of intestinal Escherichia coli producing these acids is debatab...

Physiology, fitness and disease phenotypes are complex traits exhibiting continuous variation in natural populations. To understand complex trait gene functions transgenic lines of undefined genetic background are often combined to assess quantitative phenotypes ignoring the impact of genetic polymorphisms. Here, we used inbred wild-type strains of...

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...

Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Taking a Koch’s 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 anti...

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 th...

Evolution has conserved “economic” systems that perform many functions, faster or better, with less. For example, three to five leukocyte types protect from thousands of pathogens. To achieve so much with so little, biological systems combine their limited elements, creating complex structures. Yet, the prevalent research paradigm is reductionist....

Biological reductionism vs. biological complexity.

Since the molecular characterization of Drosophila midgut progenitors in 2006, a few hundred articles studying fly intestinal stem cells have already been published. There was a relative lag phase in creating new knowledge until 2009, when at least 20 papers per year started being published on the subject and at least 40 per year since 2013. Here,...

Specific host genes and intestinal microbes, dysbiosis, aberrant immune responses and lifestyle may contribute to intestinal inflammation and cancer, but each of these parameters does not suffice to explain why sporadic colon cancer develops at an old age and only in some of the people with the same profile. To improve our understanding, longitudin...

Trauma is the most common cause of mortality among individuals aged between 1 and 44 years and the third leading cause of mortality overall in the US. In this study, we examined the effects of trauma on the expression of genes in Drosophila melanogaster, a useful model for investigating genetics and physiology. After trauma was induced by a non-let...

Pinpointing multi‐faceted, longitudinally‐changing factors that drive colorectal cancer is laborious and expensive, but doing so is necessary for more accurate CRC prognosis and therapy.

In vivo nuclear magnetic resonance spectroscopy (NMR), a non-destructive biochemical tool used for investigating live organisms, has recently been performed in studies of the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We used a novel high-resolution magic angle-spinning (HRMAS) NMR method t...

Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fu...

Following an expansion in the antibiotic drug discovery in the previous century, we now face a bottleneck in the production of new anti-infective drugs. Traditionally, chemical libraries are screened either using in vitro culture systems or in silico to identify and chemically modify small molecules with antimicrobial properties. Nevertheless, almo...

Cancer was the disease of the twentieth century. Today it is still a leading cause of death worldwide despite being intensively investigated. Abundant knowledge exists regarding the pathological and molecular mechanisms that drive healthy cells to become malignant and form metastatic tumors. The relation of oncogenes and tumor suppressors to the ge...

Immune responses are traditionally divided into the innate and the adaptive arm, both of which are present in vertebrates, while only the innate arm is found in invertebrates. Immune priming experiments in Drosophila melanogaster and other invertebrates during the last decade have challenged this dogma, questioning the boundaries between innate and...

The gastrointestinal tract is habitable by a variety of microorganisms and it is often a tissue inflicted by inflammation. Much discussion is raised in recent years about the role of microbiota in intestinal inflammation, but their role in intestinal cancer remains unclear. Here we discuss and extent our work on Drosophila melanogaster models of tu...

Patients with severe burns are highly susceptible to bacterial infection. While immunosuppression facilitates infection, the contribution of soft tissues to infection beyond providing a portal for bacterial entry remains unclear. We showed previously that glutathione S-transferase S1 (gstS1), an enzyme with conjugating activity against the lipid pe...

This book, inclusive of 22 chapters, describes novel approaches currently used for antimicrobial drug discovery, focusing on agents for use against bacterial and fungal pathogens. Specific chapters discuss: (1) concepts relevant to drug resistance; (2) microbial mechanisms related to efflux pumps and studies on their potential inhibitors; (3) impac...

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals...

[This corrects the article on p. e1002192 in vol. 7.].

Recent findings concerning Drosophila melanogaster intestinal pathology suggest that this model is well suited for the study of intestinal stem cell physiology during aging, stress and infection. Despite the physiological divergence between vertebrates and insects, the modeling of human intestinal diseases is possible in Drosophila because of the h...

In vivo magnetic resonance spectroscopy (MRS), a non-destructive biochemical tool for investigating live organisms, has yet to be used in the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We developed and implemented a high-resolution magic-angle-spinning (HRMAS) MRS method to investigate live...

High-Resolution Magic Angle Spinning (HRMAS) proton magnetic resonance spectroscopy ((1)H-MRS) is a novel non-destructive technique that improves spectral line-widths and allows high-resolution spectra to be obtained from extracts, intact cells, cell cultures, and more importantly intact tissue to investigate relationships between metabolites and c...

Transcription profile of mvfR and pqsA-E. The transcription profile was determined from the transcriptome analysis of PA14 cultures along the growth curve in LB at 37°C. (0.85 MB EPS)

Microarray data validation. The effect of PqsE on the expression of various differentially-expressed genes in the transcriptome (Table S1) was further confirmed by β-galactosidase assays derived from transcriptional fusions of the tested genes with lacZ (A–C) and by quantitative PCR (D). The levels of pqsA and pqsE gene expression by PCR were deter...

pqsE is not required for HAQs production. The levels of HHQ, PQS and HQNO were assessed by LC/MS from PA14 (circles) and pqsE− mutant (squares) cultures at various growth stages in LB at 37°C. (0.68 MB EPS)

PqsE and RhlR cooperate in the regulation of the pqs operon and of PqsE downstream genes. (A) A Venn diagram showing the number of genes co-regulated by PqsE (Table S1) and by the Las/Rhl system [42]. (B) Constitutively-expressed PqsE does not reduce the expression of pqsA in a rhlR− mutant. The expression of the pqsA gene in an rhlR− mutant consti...

Iron counteracts PQS-mediated activity. (A) The effect of iron and PQS was assessed by measuring pyocyanin production in PA14 and a PA14 pqsA::−pqsH− double-mutant constitutively expressing PqsE. PQS was added at 20 mg/L and iron at 200 µM. Asterisks show samples that are statistical significantly different (P value<0.01) from the untreated sample...

The PqsE controlled genes list. A list of genes comprising the PqsE regulated genes was generated from our transcriptional data (NCBI GEO accession number #GSE17147). The values represent ratios of differential expression between the pqsE− mutant vs. PA14 (pqsE−), mvfR− vs. PA14 (mvfR−), mvfR− harboring pDN19pqsE vs. mvfR− with pDN19 (mvfR− + PqsE)...

Transcriptional regulators controlled by the MvfR pathway. The data on the differential expression of transcription regulators was adapted from Table S1. (0.07 MB XLS)

PqsE downregulates pyoverdine production in a RhlR dependent manner. The effect of PqsE and RhlR on pyoverdine production was assessed by measuring the pyoverdine production in PA14 and mutants harboring pDN19pqsE (+PqsE) or the empty vector pDN19 cells as control. Cells were grown in D-TSB medium in 96 wells plate and were incubated at 37°C with s...

The interplay between the pqs operon and iron. The mvfR regulon components controlling (A) or controlled by (B) iron related regulators. (A) The data was adapted from Table S1. The values represent fold changes in the pqsE− mutant vs. PA14 (pqsE−), mvfR− vs. PA14 (mvfR−), mvfR− harboring pDN19pqsE vs. mvfR− + pDN19 (mvfR− + PqsE), mvfR− + PqsE trea...

Strains, plasmids and primers. The P. aeruginosa strains, plasmids and primers that were used in this study. (0.07 MB DOC)

Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regar...

Accumulating evidence suggests that hyperproliferating intestinal stem cells (SCs) and progenitors drive cancer initiation, maintenance, and metastasis. In addition, chronic inflammation and infection have been increasingly recognized for their roles in cancer. Nevertheless, the mechanisms by which bacterial infections can initiate SC-mediated tumo...

Fast-renewing tissues such as the skin and the intestine undergo continuous homeostatic turnover during which old, spent, or damaged cells are replaced by new healthy ones. These new cells are derived from stem or progenitor cell populations often interdispersed between the differentiated cells located in specialized niches. Other tissues like the...

Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mu...

List of P. aeruginosa kerV and its 196 orthologs analyzed in this manuscript. (0.34 MB DOC)

PA14, P.a.-kerV and P.a.-kerV-C growth curves in rich and minimal media. (1.33 MB TIF)

P.a.-kerV mutant exhibits similar virulence phenotype as the parental strain in a burn-mouse model. (0.70 MB TIF)

Alignment of methyltransferase type_11 motifs in PA14 kerV gene and Pfam08241. (0.24 MB TIF)

Raw data from Dictyostelium phagocytosis experiments. (0.01 MB PDF)

Conservation of host signaling pathways and tissue physiology between Drosophila melanogaster and mammals allows for the modeling of human host-pathogen interactions in Drosophila. Here we present the use of genetically tractable Drosophila models of bacterial pathogenesis to study infection with the human opportunistic pathogen Pseudomonas aerugin...

Higher induction of act88F-lacZ in transgenic flies inoculated with the CF5 versus PA14 strain. Forty female flies heterozygous for the act88F-lacZ transgene were either left untreated, or subjected to thoracic needle-mediated bacterial inoculation with PA14 or CF5 cells. Flies were ground up in PBS and LacZ levels were assesses via ONPG/LacZ liqui...

hep1 mutation allows higher bacterial proliferation in the thorax but not the abdomen. Comparison of CFUs over time of wild-type and hep1 fly thoraces (A) and abdomens (B) collected from the same flies that had been inoculated in the thorax. Error bars indicate Standard Deviation of the mean. (0.17 MB PDF)

Statistical analysis of fly survival post P. aeruginosa infection using the Kaplan-Meier (1) and Cox (2) models. Comparison of the survival curve P values as derived from the Mantel-Haenszel test using the Kaplan-Meier estimate of survival (1); and the likelihood ratio test using the Cox proportional hazards regression model (2). P values of less t...

Hep mediates collective expression of SMGs. Expression ratio of SMGs in wild-type and hep1 flies in thoracic injured, or injured and inoculated in the thorax with CF5 strain conditions 1 h post-treatment. The relative expression ratio levels of SMGs for each condition were calculated versus naïve for each genotype. (0.17 MB PDF)

hep1 mutation does not disrupt muscle structure. Wild-type (A) and hep1 (B) fly muscle structure, viewed by transmission electron microscopy. (0.17 MB PDF)

Student t-test P-values of the 20 SMGs assessing the difference in expression in PA14 vs CF5 needle-pricking inoculated flies (1, 6 and 12 hours post- thoracic or abdominal treatment). (0.02 MB PDF)

Gst2 and TpnC41C RNA levels are reduced in Gst2 mutant and TpnC41C RNAi flies, respectively. (A) Relative RNA levels of TpnC41C, Gst2 and Dipt in flies of the UAS-yuriRNAi/+;dMef2-GAL4/+ and UAS-TpnC41CRNAi/+;dMef2-GAL4/+ genotypes, presented as Control RNAi and TpnC41C RNAi respectively. (B,C) Relative RNA levels of Gst2, act88F and Dipt in flies...

Muscle specific hep overexpression increases fly survival of PA14 infection. (A) Survival kinetics of wild-type flies with (Mef-G4/U-hep), or without (Mef-G4/+), specific overexpression of Hep in skeletal muscle following thoracic PA14 infection. (B) Hep-overexpressing flies had augmented act88F (*P = 0.007; two tailed t-test), but not Dipt, transc...

The stable subdivision of Drosophila limbs into anterior and posterior compartments is a consequence of asymmetrical signalling by Hedgehog (Hh), from the posterior to anterior cells. The activity of the homeodomain protein Engrailed in posterior cells helps to generate this asymmetry by inducing the expression of Hh in the posterior compartment an...

Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows se...

Insights into the host factors and mechanisms mediating the primary host responses after pathogen presentation remain limited, due in part to the complexity and genetic intractability of host systems. Here, we employ the model Drosophila melanogaster to dissect and identify early host responses that function in the initiation and progression of Pse...

We found that the ingestion of Cryptococcus neoformans by Drosophila melanogaster resulted in the death of the fly but that the ingestion of Saccharomyces cerevisiae or the nonpathogenic Cryptococcus kuetzingii or Cryptococcus laurentii did not. The C. neoformans protein kinase A and RAS signal transduction pathways, previously shown to be involved...

Groucho (Gro) is the founding member of a family of transcriptional co-repressors that are recruited by a number of different transcription factors. Drosophila has a single gro gene, whose loss of function affects processes ranging from sex determination to embryonic patterning and neuroblast specification. We have characterized a function of Gro i...

The E(spl) complex (E(spl)-C) contains three different classes of genes that are downstream of Notch signaling. The bHLH genes mediate the Notch signal by repressing proneural gene activity, for example during the singularization of mechanosensory organ precursor cells (SOPs). Genes of the second class, the E(spl) m4/malpha family, antagonize this...

The E(spl) complex (E(spl)-C) contains three different classes of genes that are downstream of Notch signaling. The bHLH genes mediate the Notch signal by repressing proneural gene activity, for example during the singularization of mechanosensory organ precursor cells (SOPs). Genes of the second class, the E(spl) m4/mα family, antagonize this proc...

Intercellular signalling mediated by Notch proteins is crucial to many cell fate decisions in metazoans. Its profound effects on cell fate and proliferation require that a complex set of responses involving positive and negative signal transducers be orchestrated around each instance of signalling. In Drosophila the basic-helix-loop-helix (bHLH) re...

A common consequence of Notch signalling in Drosophila is the transcriptional activation of seven Enhancer of split [E(spl)] genes, which encode a family of closely related basic-helix-loop-helix transcriptional repressors. Different E(spl) proteins can functionally substitute for each other, hampering loss-of-function genetic analysis and raising...