Role of Environmental Exposure to Toxins and Microbial Infections in Autism

2014 ◽  
pp. 15
Author(s):  
Hari Cohly ◽  
Nataliya Kostyuk ◽  
Rajendram Rajnarayanan
Keyword(s):  
Environmental Exposure ◽  
Microbial Infections

scholarly journals Thioester-Containing Protein-4 Regulates the Drosophila Immune Signaling and Function against the Pathogen Photorhabdus

2016 ◽  
Vol 9 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Upasana Shokal ◽  
Ioannis Eleftherianos
Keyword(s):  
Immune Response ◽  
Photorhabdus Luminescens ◽  
Human Pathogen ◽  
Loss Of Function ◽  
Phenoloxidase Activity ◽  
Microbial Infections ◽  
Immune Pathways ◽  
And Function ◽  
Important Progress

Despite important progress in identifying the molecules that participate in the immune response of Drosophila melanogaster to microbial infections, the involvement of thioester-containing proteins (TEPs) in the antibacterial immunity of the fly is not fully clarified. Previous studies mostly focused on identifying the function of TEP2, TEP3 and TEP6 molecules in the D. melanogaster immune system. Here, we investigated the role of TEP4 in the regulation and function of D. melanogaster host defense against 2 virulent pathogens from the genus Photorhabdus, i.e. the insect pathogenic bacterium Photorhabdus luminescens and the emerging human pathogen P. asymbiotica. We demonstrate that Tep4 is strongly upregulated in adult flies following the injection of Photorhabdus bacteria. We also show that Tep4 loss-of-function mutants are resistant to P. luminescens but not to P. asymbiotica infection. In addition, we find that inactivation of Tep4 results in the upregulation of the Toll and Imd immune pathways, and the downregulation of the Jak/Stat and Jnk pathways upon Photorhabdus infection. We document that loss of Tep4 promotes melanization and phenoloxidase activity in the mutant flies infected with Photorhabdus. Together, these findings generate novel insights into the immune role of TEP4 as a regulator and effector of the D. melanogaster antibacterial immune response.

scholarly journals Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

2013 ◽  
Vol 7 (1) ◽  
pp. 34-52 ◽  
Author(s):  
Christina Kourtesi ◽  
Anthony R Ball ◽  
Ying-Ying Huang ◽  
Sanjay M Jachak ◽  
D Mariano A Vera ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Major Theme ◽  
Clinical Implementation ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Development Path ◽  
Microbial Infections ◽  
Efflux Pump Inhibitors ◽  
Shed Light

Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.

scholarly journals Hypothetical roadmap towards endometriosis: prenatal endocrine-disrupting chemical pollutant exposure, anogenital distance, gut-genital microbiota and subclinical infections

2020 ◽  
Vol 26 (2) ◽  
pp. 214-246 ◽  
Author(s):  
Pilar García-Peñarrubia ◽  
Antonio J Ruiz-Alcaraz ◽  
María Martínez-Esparza ◽  
Pilar Marín ◽  
Francisco Machado-Linde
Keyword(s):  
Prenatal Exposure ◽  
Genital Tract ◽  
Endocrine Disrupting Chemicals ◽  
Active Role ◽  
Faecal Microbiota ◽  
Clinical Progression ◽  
Anogenital Distance ◽  
Endocrine Disrupting ◽  
Microbial Infections

Abstract BACKGROUND Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases. OBJECTIVE AND RATIONALE In this review, we sought to respond to the main research question related to the aetiology of endometriosis. We provide a model pointing out several risk factors that could explain the development of endometriosis. The hypothesis arises from bringing together current findings from large distinct areas, linking high prenatal exposure to environmental endocrine-disrupting chemicals with a short anogenital distance, female genital tract contamination with the faecal microbiota and the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. SEARCH METHODS We performed a search of the scientific literature published until 2019 in the PubMed database. The search strategy included the following keywords in various combinations: endometriosis, anogenital distance, chemical pollutants, endocrine-disrupting chemicals, prenatal exposure to endocrine-disrupting chemicals, the microbiome of the female reproductive tract, microbiota and genital tract, bacterial vaginosis, endometritis, oestrogens and microbiota and microbiota–immune system interactions. OUTCOMES On searching the corresponding bibliography, we found frequent associations between environmental endocrine-disrupting chemicals and endometriosis risk. Likewise, recent evidence and hypotheses have suggested the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Hence, we can envisage a direct relationship between higher prenatal exposure to oestrogens or estrogenic endocrine-disrupting compounds (phthalates, bisphenols, organochlorine pesticides and others) and a shorter anogenital distance, which could favour frequent postnatal episodes of faecal microbiota contamination of the vulva and vagina, producing cervicovaginal microbiota dysbiosis. This relationship would disrupt local antimicrobial defences, subverting the homeostasis state and inducing a subclinical inflammatory response that could evolve into a sustained immune dysregulation, closing the vicious cycle responsible for the development of endometriosis. WIDER IMPLICATIONS Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions.

Alzheimer’s Disease and Environmental Exposure to Lead: The Epidemiologic Evidence and Potential Role of Epigenetics

2012 ◽  
Vol 9 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Kelly M. Bakulski ◽  
Laura S. Rozek ◽  
Dana C. Dolinoy ◽  
Henry L. Paulson ◽  
Howard Hu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Exposure ◽  
Potential Role ◽  
Epidemiologic Evidence

An update on the role of miRNA-155 in pathogenic microbial infections

2015 ◽  
Vol 17 (9) ◽  
pp. 613-621 ◽  
Author(s):  
Fu-Rong Zeng ◽  
Li-Jun Tang ◽  
Ye He ◽  
R.C. Garcia
Keyword(s):  
Microbial Infections

scholarly journals TmSpz4 Plays an Important Role in Regulating the Production of Antimicrobial Peptides in Response to Escherichia coli and Candida albicans Infections

2020 ◽  
Vol 21 (5) ◽  
pp. 1878 ◽  
Author(s):  
Tariku Tesfaye Edosa ◽  
Yong Hun Jo ◽  
Maryam Keshavarz ◽  
Young Min Bae ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Candida Albicans ◽  
Immune Responses ◽  
Fungal Infections ◽  
Larval Survival ◽  
Gram Negative Bacteria ◽  
Functional Importance ◽  
E Coli ◽  
Microbial Infections

Spätzle family proteins activate the Toll pathway and induce antimicrobial peptide (AMP) production against microbial infections. However, the functional importance of Tmspätzle4 (TmSpz4) in the immune response of Tenebrio molitor has not been reported. Therefore, here, we have identified and functionally characterized the role of TmSpz4 against bacterial and fungal infections. We showed that TmSpz4 expression was significantly induced in hemocytes at 6 h post-injection with Escherichia coli, Staphylococcus aureus, and Candida albicans. TmSpz4 knock-down significantly reduced larval survival against E. coli and C. albicans. To understand the reason for the survivability difference, the role of TmSpz4 in AMP production was examined in TmSpz4-silenced larvae following microbe injection. The AMPs that are active against Gram-negative bacteria, including TmTenecin-2, TmTenecin-4, TmAttacin-1a, TmDefensin-2, and TmCecropin-2, were significantly downregulated in response to E. coli in TmSpz4-silenced larvae. Similarly, the expression of TmTenecin-1, TmTenecin-3, TmThaumatin-like protein-1 and -2, TmDefensin-1, TmDefensin-2, and TmCecropin-2 were downregulated in response to C. albicans in TmSpz4-silenced larvae. In addition, the transcription factor NF-κB (TmDorX1 and TmDorX2) expression was significantly suppression in TmSpz4-silenced larvae. In conclusion, these results suggest that TmSpz4 plays a key role in regulating immune responses of T. molitor against to E. coli and C. albicans.

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