Project description:The goals of this study were to investigate whether two anesthesia regimens, with and without N2O, and bacterial colonization influence respiratory complications after major abdominal surgery for cancer.
Project description:We sought to find if epigenetic drugs had chromatin context-dependent effects on CRISPR-Cas9 efficiency and DNA double-strand break repair. We performed a multiplexed drug screen in a reporter cell line containing 19 sequencing based pathway reporters. This submission contains high throughput sequencing data of the pathway reporters, their mapping and mutation readout. It also contains the raw pA-DamID data for H3K27me3, H3K9me2, H3K9me3 and "Dam-only" samples in RPE-1 cells.
Project description:Regulated host cell death is part of a plant defense strategy against pathogens but it is also involved in accommodating certain beneficial root microbes. We have identified extracellular metabolites and intracellular metabolic signals that contribute to beneficial root fungal endophyte colonization, and uncovered a conserved cell death mechanism likely co-opted for establishing plant-endophyte symbiosis.
Project description:Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans’ perspective, but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to Neisseria musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from lung, blood and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria.
Project description:Asymptomatic colonization of the upper respiratory tract is a common trait of the two exclusive human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. In vivo models of pathogenic neisserial infections are heterologous systems that permit short-term persistence but do not fully recapitulate infections in humans. Studying Neisseria musculi (Nmus), an oral commensal, in laboratory mice allows investigation of Neisseria-host interactions that avoids host restriction barriers. Nmus produces smooth and rough morphotypes on solid media. We compared the in vitro phenotypes, biofilm transcriptomes, and in vivo colonization patterns and burdens of the Nmus morphotypes. We observed that the two morphotypes differ in biofilm formation, aggregation, pilin production, and transformation frequency in vitro. These phenotypes strongly correlated with differential expression of a set of genes in the Nmus biofilms including those that encoded factors for bacterial attachment. In vivo, the smooth morphotype stably colonized the oral cavities of all inoculated A/J and C57BL/6J mice at higher burdens compared to the rough. Following nasal inoculations, we detected transient Nmus nasal colonization. The smooth morphotype was able to reach higher burdens more quickly in the nasal cavity and on oral swabs following dissemination to the oral cavity. Gut colonization burdens fluctuated over time. Interestingly, both morphotypes colonized the oral cavities of A/Js at higher magnitudes than in C57BL/6Js. Collectively, our results demonstrate that colonization by Nmus can be affected by various factors including Nmus morphotypes, inoculation routes, anatomical niches, and host backgrounds. The Nmus-mouse model can use variable morphotype-host combinations to study the dynamics of neisserial asymptomatic colonization and persistence in multiple extragenital niches.
Project description:Burkholderia cenocepacia J2315 wild type and adaptive mutants with elevated resistance to antibiotics were exposed to sub-inhibitory concentrations of drugs
Project description:Mycobacterium abscessus is an opportunistic pathogen notorious for its resistance to most classes of antibiotics and low cure rates. In addition to the highly impermeable mycomembrane, M. abscessus carries an array of shared and species-specific defence mechanisms. However, it remains unknown whether M. abscessus’ antibiotic stress response is fine-tuned or an all-or-nothing response. A deeper understanding of underlying resistance and tolerance mechanisms is pivotal in development of targeted therapeutic regimens. We elucidate the transcriptomic response of M. abscessus to antibiotics recommended in treatment guidelines. The M. abscessus ATCC 19977 strain was used. Bacteria were subjected to sub-inhibitory concentrations of drugs for 4- and 24-hours, followed by RNA sequencing. In addition, time-kill kinetic analysis was performed using bacteria after pre-exposure to clarithromycin, amikacin or tigecycline for 24-hours. Lastly, Pan-genome analysis of 35 strains from all three subspecies was performed. Mycobacterium abscessus shows both drug-specific and communal transcriptomic responses to antibiotic exposure. Key features of its tolerance to antibiotics are drug-specific converting enzymes, target protection and shifts in its respiratory chain and metabolic state. The observed transcriptomic responses are likely not strain-specific, as genes involved in tolerance are found in all included strains, with the exception of erm(41) in M. abscessus subspecies massiliense. Due to the communal response elicited by ribosomal-targeting antibiotics, exposure to any of these drugs rapidly induces tolerance mechanisms that decrease susceptibility to ribosome-targeting drugs from multiple classes. Screening high-risk patients (e.g. those with bronchiectasis) for M. abscessus infection prior to starting macrolide or aminoglycoside maintenance therapy is warranted.
Project description:Fungal colonization leads to enhanced granulopoiesis in the bone marrow. The purpose of the study is to understand the alteration of cell compostions and transcriptional profile under CA colonization.