A5051082047- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Vibrio bacteria research studies
- Escherichia coli research studies
- Gut microbiota and health
- Salmonella and Campylobacter epidemiology
- Probiotics and Fermented Foods
- RNA modifications and cancer
- Antibiotic Resistance in Bacteria
- Clostridium difficile and Clostridium perfringens research
- Bacterial biofilms and quorum sensing
- Genomics and Phylogenetic Studies
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Antimicrobial Resistance in Staphylococcus
- Streptococcal Infections and Treatments
- Tryptophan and brain disorders
- Epigenetics and DNA Methylation
- Digestive system and related health
- RNA Interference and Gene Delivery
- Genetic factors in colorectal cancer
- Helicobacter pylori-related gastroenterology studies
- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
University of Toronto
2014-2025
University of Washington
2003-2019
Sumitomo Electric Industries (United States)
2013
Weatherford College
2013
Centre Hospitalier de Beauvais
2013
The Ohio State University
2012-2013
University of New Brunswick
2009
Canada Research Chairs
2009
Sidney Kimmel Cancer Center
2006
Seattle University
2003
Horizontal gene transfer plays a major role in microbial evolution. However, newly acquired sequences can decrease fitness unless integrated into preexisting regulatory networks. We found that the histone-like nucleoid structuring protein (H-NS) selectively silences horizontally genes by targeting with GC content lower than resident genome. Mutations hns are lethal Salmonella accompanied compensatory mutations other loci. Thus, H-NS provides previously unrecognized mechanism of bacterial...
Summary Many surface proteins are thought to be anchored the cell wall of Gram‐positive bacteria via their C ‐terminus. Cell anchoring requires a specific sorting signal, normally located at predicted ‐terminus proteins. Here we show that when placed into middle polypeptide chain, signal causes cleavage precursor as well its N‐ terminal fragment, while ‐terminal fragment remains within cytoplasm. N sequencing suggests site is between threonine (T) and glycine (G) LPXTG motif, signature...
The aryl hydrocarbon receptor (AhR) is a sensor of products tryptophan metabolism and potent modulator immunity. Here, we examined the impact AhR in tumor-associated macrophage (TAM) function pancreatic ductal adenocarcinoma (PDAC). TAMs exhibited high activity Ahr-deficient macrophages developed an inflammatory phenotype. Deletion Ahr myeloid cells or pharmacologic inhibition reduced PDAC growth, improved efficacy immune checkpoint blockade, increased intra-tumoral frequencies IFNγ+CD8+ T...
H-NS and Lsr2 are nucleoid-associated proteins from Gram-negative bacteria Mycobacteria , respectively, that play an important role in the silencing of horizontally acquired foreign DNA is more AT-rich than resident genome. Despite fact dissimilar sequence structure, they serve apparently similar functions can functionally complement one another. The mechanism by which these xenogeneic silencers selectively target has been enigmatic. We performed high-resolution protein binding microarray...
Summary Cationic antimicrobial peptides (CAMP) represent a conserved and highly effective component of innate immunity. During infection, the Gram‐negative pathogen Salmonella typhimurium induces different mechanisms CAMP resistance that promote pathogenesis in animals. This study shows exposure S. to sublethal concentrations activates PhoP/PhoQ RpoS virulence regulons, while repressing transcription genes required for flagella synthesis invasion‐associated type III secretion system. We...
Summary Analysis of the transcriptome slyA mutant Salmonella enterica serovar Typhimurium revealed that many SlyA‐dependent genes, including pagC , pagD ugtL mig‐14 virK phoN pgtE pipB2 sopD2 pagJ and pagK are also controlled by PhoP/PhoQ regulatory system. Many SlyA‐ PhoP/PhoQ‐co‐regulated genes have functions associated with bacterial envelope, some been directly implicated in virulence resistance to antimicrobial peptides. Purified His‐tagged SlyA binds promoters regions homologous a...
Bacterial nucleoid-associated proteins play important roles in chromosome organization and global gene regulation. We find that Lsr2 of Mycobacterium tuberculosis is a unique protein binds AT-rich regions the genome, including genomic islands acquired by horizontal transfer encoding major virulence factors, such as ESX secretion systems, lipid factors PDIM PGL, PE/PPE families antigenic proteins. Comparison genome-wide binding data with expression indicates results transcriptional...
Summary The two‐component system SsrA–SsrB activates expression of a type III secretion required for replication in macrophages and systemic infection mice. Here we characterize the SsrB‐dependent regulation genes within Salmonella pathogenicity island 2 (SPI‐2). Primer extension DNase I footprinting identified multiple SsrB‐regulated promoters SPI‐2 located upstream ssaB , sseA ssaG ssaM . We previously demonstrated that ssrA ssrB transcription is uncoupled. Overexpression SsrB absence its...
ABSTRACT Elongation factor P (EF-P) is a universally conserved bacterial translation homologous to eukaryotic/archaeal initiation 5A. In Salmonella , deletion of the efp gene results in pleiotropic phenotypes, including increased susceptibility numerous cellular stressors. Only limited number proteins are affected by loss EF-P, and it has recently been determined that EF-P plays critical role rescuing ribosomes stalled at PPP PPG peptide sequences. Here we present an unbiased vivo...
Inflammatory bowel disease patients have a greatly increased risk of developing colitis-associated colon cancer (CAC); however, the basis for inflammation-induced genetic damage requisite neoplasia is unclear. Using three models CAC, we find that sustained inflammation triggers 8-oxoguanine DNA lesions. Strikingly, antioxidants or iNOS inhibitors reduce and polyps in CAC models. Because mismatch repair (MMR) system repairs frequently defective colorectal (CRC), test whether mediates...
Microbiome research needs comprehensive repositories of cultured bacteria from the intestine mammalian hosts. We expanded mouse intestinal bacterial collection (www.dsmz.de/miBC) to 212 strains, all publicly available and taxonomically described. This includes strain-level diversity, small-sized bacteria, previously undescribed taxa (one family, 10 genera, 39 species). enabled metagenome-educated prediction synthetic communities (SYNs) that capture key functional differences between...
Bacteriophage muralytic enzymes degrade the cell wall envelope of staphylococci to release phage particles from bacterial cytoplasm. Murein hydrolases staphylococcal phages φ11, 80α, 187, Twort, and φPVL harbor a central domain that displays sequence homology known<i>N-</i>acetylmuramyl-l-alanyl amidases; however, their precise cleavage sites on peptidoglycan have thus far not been determined. Here we examined properties φ11 enzyme hydrolyze either or purified anchor structures attached...
Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Our previous vitro biochemical studies showed that DNA-bridging protein, property shared by H-NS-like proteins gram-negative bacteria. Here we vivo evidence based on genetic complementation experiments functional analog of H-NS, the first such identified gram-positive We show lsr2 can complement phenotypes to hns mutations Escherichia coli, including beta-glucoside utilization, mucoidy, motility, hemolytic...
The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer fitness consequences associated foreign gene acquisition. Loss of results in severe growth defects Salmonella, but underlying reasons were unclear. An experimental evolution approach was employed determine which secondary mutations could compensate for loss Salmonella. Six independently derived S. Typhimurium hns mutant strains serially passaged 300 generations...