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Biology subjects

Eid, W.

Publications and source records attributed to Eid, W..

3 recordsLinked to original sources

Municipal Wastewater in Ottawa, Canada contains a reservoir of bacteriophages with clinically relevant Escherichia coli and Klebsiella pneumoniae Hosts

The recent rise of antimicrobial resistant bacteria in health care and environmental settings has been detrimental to the feasibility of antibiotic treatments for patients and agricultural applications. Along with this escalating issue, a resurgence of bacteriophage research has occurred, and phage therapy is proving to be a powerful case-specific alternative. However, a centralized source of phages that are accessible, abundant, and characterized as candidates for potential use in therapeutic applications remains to be fully established. This study aims to identify the range of bacteriophages available in municipal wastewater from Ottawa, Ontario that can infect and lyse Escherichia coli O1:K1:H7 and Klebsiella pneumoniae K3 hosts. Building-level sewer shed, influent, and primary sludge samples were screened for the presence of these phages which were then isolated through several rounds of plaque purification, sequenced by Nanopore technology, and annotated. Ten phages belonging to the genus Kayfunavirus, Vectrevirus, Kuravirus, or Sugarlandvirus were identified and bio-banked from different types of wastewater at several time points. These phages are 96-99% identical to phages isolated in Germany, Switzerland, and Spain, but contain divergent structural and metabolic genes. This work contributes to the ever-growing database of sequenced phages, provided with a physical archive of the organisms, and helps uncover the extent of phage biodiversity at different levels of wastewater treatment facilities that are readily available for screening in phage therapy applications.

microbiology↗

Urban wastewater contains a functional human antibody repertoire of mucosal origin

Wastewater-based surveillance of human disease offers timely insights to public health, helping to mitigate infectious disease outbreaks and decrease downstream morbidity and mortality. These systems rely on nucleic acid amplification tests for monitoring disease trends, while antibody-based seroprevalence surveys gauge community immunity. However, serological surveys are resource-intensive and subject to potentially long lead times and sampling bias. We identified and characterized a human antibody repertoire, predominantly secretory IgA, isolated from a central wastewater treatment plant and building-scale wastewater collection points. These antibodies partition to the solids fraction and retain immunoaffinity for SARS-CoV-2 and Influenza A virus antigens. This stable pool could enable real-time tracking of correlates of vaccination, infection, and immunity, aiding in establishing population-level thresholds for immune protection and assessing the efficacy of future vaccine campaigns, particularly those that are designed to induce humoral mucosal immunity.

immunology↗

The Human Exonuclease-1 Interactome And Phosphorylation Sites

Error-free repair of DNA double-strand break is orchestrated by homologous recombination (HR) pathways and requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM execute extensive resection of DNA ends to produce 3-overhangs, which are key intermediates for downstream steps of HR. To help shedding light on regulatory aspects of DNA repair pathways in which EXO1 participates, we set out to identify proteins interacting with EXO1. Affinity purification of EXO1 followed by Orbitrap mass spectrometry led to the identification of novel partners that are involved in RNA processing or that are the causative agents of rare X-linked disorders. Depletion of a selected subset of EXO1 interacting proteins led to reduction of the DNA damage response. Among those, we examined the RRP5-homologue and NF{kappa}B-interacting protein PDCD11/ALG-4, which has roles in apoptosis and is a putative driver gene in cutaneous T-cell lymphoma. We provide evidence that depletion of PDCD11 decreased the formation of {gamma}H2AX foci and the phosphorylation of DNA damage response signaling intermediates in response to camptothecin or bleomycin, resulting in increased cellular resistance to DNA damage. Furthermore, extensive coverage of EXO1 sequence (>85%) by mass spectrometry allowed conducting an in-depth analysis of its phosphorylation sites, with the identification of 26 residues that are differentially modified in untreated conditions or upon induction of DNA damage.\n\nAs a whole, these results provide the basis for future in-depth studies on novel roles of EXO1 in genome stability and indicate targets for pharmacological inhibition of pathways of cancer development.\n\nHIGHLIGHTS O_LIProteome-wide analysis of Exonuclease-1 (EXO1) interacting proteins revealed novel partners involved in RNA processing or that are the causative agents of rare X-linked disorders.\nC_LIO_LIWe provide evidence for a role of PDCD11 in the DNA Damage Response.\nC_LIO_LIWe conducted a comprehensive identification of EXO1 phosphorylation sites.\nC_LI

cell biology↗