Denice Bay

Denice Bay
University of Manitoba | UMN · Department of Medical Microbiology and Infectious Diseases

Ph.D

About

59
Publications
5,598
Reads
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1,083
Citations
Introduction
Examination of bacterial multidrug transporters and their lipid dependence to understand their function, evolution, and structural biology using a multidisciplinary approach involving molecular biology, microbiology, biochemistry, biophysics, and bioinformatics.
Additional affiliations
June 2015 - present
University of Manitoba
Position
  • Professor (Assistant)
Description
  • My goal is to analyze multidrug resistance membrane protein transport activity, evolution, and structural biology using a multidisciplinary approach that involves molecular biology, microbiology, biochemistry, biophysics, and bioinformatic techniques.
July 2006 - May 2015
The University of Calgary
Position
  • Research Associate

Publications

Publications (59)
Article
Full-text available
Bacterial resistance to the antiseptic chlorhexidine (CHX), is a growing problem, recently shown to be caused by deleterious mutations to the phospholipid transport system component (mlaA) as well as efflux pump overexpression. Comparisons of CHX resistance mechanisms, such as porin deletions (ompCF), and over-expressed efflux pumps (acrB, qacE, ac...
Article
In this study, we isolated and molecularly characterized 10 (1.6%) C. difficile isolates from 644 commercially available raw meat samples. Molecular typing by PFGE and ribotyping revealed NAP and ribotypes commonly associated with human clinical cases, suggesting retail meat could be a possible source of transmission warranting further investigatio...
Article
Objectives: To determine whether the genotypic resistance profile inferred from WGS could accurately predict phenotypic resistance for ESBL-producing Escherichia coli isolated from patient samples in Canadian hospital laboratories. Methods: As part of the ongoing CANWARD study, 671 E. coli were collected and phenotypically confirmed as ESBL prod...
Article
Full-text available
Qac efflux pumps from proteobacterial multidrug-resistant plasmids are integron-encoded and confer resistance to quaternary ammonium compound (QAC) antiseptics, however, many are uncharacterized and misannotated. A survey of >2000 plasmid-encoded qac identified 37 unique qac sequences that correspond to one of five representative motifs: QacE, QacE...
Article
Full-text available
Chlorhexidine (CHX) is an essential medicine used as a topical antiseptic in skin and oral healthcare treatments. The widespread use of CHX has increased concerns regarding the development of antiseptic resistance in Enterobacteria and its potential impact on cross-resistance to other antimicrobials. Similar to other cationic antiseptics, resistanc...
Article
Full-text available
Outer membrane vesicles (OMVs) produced by Gram-negative bacteria are mediators of cell survival and pathogenesis by facilitating virulence factor dissemination and resistance to antimicrobials. Studies of OMV properties often focus on hypervesiculating Escherichia coli mutants that have increased OMV production when compared to their corresponding...
Article
Lefamulin is a novel oral and intravenous (IV) pleuromutilin developed as a twice-daily treatment for community-acquired bacterial pneumonia (CABP). It is a semi-synthetic pleuromutilin with a chemical structure that contains a tricyclic core of five-, six-, and eight-membered rings and a 2-(4-amino-2-hydroxycyclohexyl)sulfanylacetate side chain ex...
Article
Full-text available
Biocides such as quaternary ammonium compounds (QACs) are potentially important contributors towards bacterial antimicrobial resistance development, however, their contributions are unclear due to a lack of internationally recognized biocide testing standards. Methods to detect QAC tolerance are limited to laborious traditional antimicrobial suscep...
Article
Here, we characterize the fosA genes from three E. coli clinical isolates recovered from Canadian patients. Each fosA sequence was individually overexpressed in E. coli BW25113 and antimicrobial susceptibility testing was performed to assess their role in fosfomycin resistance. The findings from this study identify and functionally characterize Fos...
Article
This study characterized the function of antimicrobial-resistant phenotypes attributed to plasmid-encoded guanidinium-selective small multidrug resistance (Gdm/SugE) efflux pumps. These sequences are frequently monitored as biocide resistance markers in antimicrobial resistance surveillance studies. Our findings reveal that enterobacterial gdm sequ...
Preprint
Full-text available
Quaternary ammonium compounds (QACs) benzalkonium (BZK) and cetrimide (CET) are common disinfectants used to inhibit or eradicate Gram-negative bacteria in clinical and agricultural products. QAC tolerance in Escherichia coli and other Enterobacterales species can confer cross-resistance to various clinically used antibiotics, making it important t...
Article
Omadacycline is a novel aminomethylcycline antibiotic developed as a once-daily, intravenous and oral treatment for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP). Omadacycline, a derivative of minocycline, has a chemical structure similar to tigecycline with an alkylaminomethyl group re...
Article
Among 162 isolates of extended-spectrum beta-lactamase-(ESBL)-producing Escherichia coli recovered from the urine of Canadian patients (2007-2017), five (3.1%) were not susceptible in vitro to fosfomycin (MIC ≥128 μg/mL). These isolates underwent whole genome sequencing to assess for the presence of fos genes. The fosA3 gene was detected in one iso...
Article
Full-text available
Background and aim: We previously reported the anti-atherogenic properties of wild rice in low-density lipoprotein receptor knockout (LDL-r-KO) mice. The present study aimed to discover the mechanism of action for such effects. Materials: Fecal and plasma samples from the wild rice treated and control mice were used. Fecal bacterial population w...
Preprint
Full-text available
Small multidrug resistance (SMR) efflux pump genes are commonly identified from integrons carried by multidrug-resistant (MDR) plasmids. SMR pumps are annotated as 'qac' for their ability to confer resistance to quaternary ammonium compounds (QACs) but few qac are characterized to date. Hence, we have examined SMR sequence diversity, antimicrobial...
Article
Objectives: The CANWARD surveillance study was established in 2007 to annually assess the in vitro susceptibilities of a variety of antimicrobial agents against bacterial pathogens isolated from patients receiving care in Canadian hospitals. Methods: 42 936 pathogens were received and CLSI broth microdilution testing was performed on 37 355 bact...
Article
Diets and lifestyle significantly contribute to risk factors for atherosclerotic vascular disease. Diets with cholesterol-lowering and antioxidant properties have been shown to prevent atherogenesis in experimental animals. Our laboratory has reported significant antiatherogenic effects of various functional foods including wild rice, kgengwe seeds,...
Article
EmrE is the archetypical member of the small multidrug resistance transporter family and confers resistance to a wide range of disinfectants and dyes known as quaternary cation compounds (QCCs). The aim of this study was to examine which conserved amino acids play an important role in substrate selectivity. On the basis of a previous analysis of Em...
Article
Full-text available
Bacterial resistance to biocides used as antiseptics, dyes, and disinfectants is a growing concern in food preparation, agricultural, consumer manufacturing, and health care industries, particularly among Gram-negative Enterobacteriaceae, some of the most common community and healthcare-acquired bacterial pathogens. Biocide resistance is frequently...
Chapter
Small multidrug resistance (SMR) transporters confer resistance to a variety of quaternary cation compound antimicrobials. These secondary active transporters are the smallest known transporters and have been demonstrated to function within the membrane. The focus of this chapter explores and updates SMR family diversity and reviews current structu...
Article
Escherichia coli possesses many secondary active multidrug resistance transporters (MDTs) that confer overlapping substrate resistance to a broad range of antimicrobials via proton and/or sodium motive force. It is uncertain whether redundant MDTs uniquely alter cell survival when cultures grow planktonically or as biofilms. In this study, the plan...
Article
The second messenger cyclic diguanylate (c-di-GMP) controls diverse cellular processes among bacteria. Diguanylate cyclases synthesize c-di-GMP, whereas it is degraded by c-di-GMP-specific phosphodiesterases (PDEs). Nearly 80% of these PDEs are predicted to depend on the catalytic function of glutamate-alanine-leucine (EAL) domains, which hydrolyze...
Article
Full-text available
Background Redox enzyme maturation proteins (REMPs) describe a diverse family of prokaryotic chaperones involved in the biogenesis of anaerobic complex iron sulfur molybdoenzyme (CISM) respiratory systems. Many REMP family studies have focused on NarJ subfamily members from Escherichia coli: NarJ, NarW, DmsD, TorD and YcdY. The aim of this bioinfor...
Article
Full-text available
EmrE is a member of the small multidrug resistance (SMR) protein family in Escherichia coli. EmrE confers resistance to a wide variety of quaternary cation compounds (QCCs) as an efflux transporter driven by proton motive force. The purification yield of most membrane proteins are challenging because of difficulties in over expressing, isolating an...
Article
Bacterial membrane compositions vary widely between phyla and within related species. The types of lipids within membranes are as diverse as the selective pressures that influence bacterial lifestyles such as their mode of respiration and habitat. This study has examined the extent that respiration and habitat affect bacterial fatty acid (FA) and p...
Article
Redox enzyme maturation proteins (REMPs) are system-specific chaperones required for the maturation of complex iron sulfur molybdoenzymes that are important for anaerobic respiration in bacteria. Although they perform similar biological roles, REMPs are strikingly different in terms of sequence, structure, systems biology, and type of terminal elec...
Article
Full-text available
In Escherichia coli, the small multidrug resistance (SMR) transporter protein EmrE confers host resistance to a broad range of toxic quaternary cation compounds (QCC) via proton motive force in the plasma membrane. Biologically produced QCC also act as EmrE osmoprotectant substrates within the cell and participate in host pH regulation and osmotic...
Article
Full-text available
The twin-arginine translocation (Tat) protein export system enables the transport of fully folded proteins across a membrane. This system is composed of two integral membrane proteins belonging to TatA and TatC protein families and in some systems a third component, TatB, a homolog of TatA. TatC participates in substrate protein recognition through...
Article
Functional characterization of the multidrug resistance CmbT transporter was performed in Lactococcus lactis. The cmbT gene is predicted to encode an efflux protein homologous to the multidrug resistance major facilitator superfamily. The cmbT gene (1377 bp) was cloned and overexpressed in L. lactis NZ9000. Results from cell growth studies revealed...
Article
Small multidrug resistance (SMR) protein family members confer bacterial resistance to toxic antiseptics and are believed to function as dual topology oligomers. If dual topology is essential for SMR activity, then the topology bias should change as bacterial membrane lipid compositions alter to maintain a "neutral" topology bias. To test this hypo...
Article
Full-text available
The small multidrug resistance (SMR) transporter protein EmrE in Escherichia coli is known to confer resistance to toxic antiseptics classified as quaternary cation compounds (QCCs). Naturally derived QCCs synthesized during metabolic activities often act as osmoprotectants, such as betaine and choline, and participate in osmotic homoestasis. The g...
Article
Escherichia coli EmrE protein is the archetypical member of the small multidrug resistance protein family in bacteria and confers host resistance to a wide assortment of toxic quaternary cation compounds by secondary active efflux. This protein can form a variety of multimers under various membrane mimetic conditions, and the consensus of most bioc...
Article
Beta-barrel proteins are the main transit points across the mitochondrial outer membrane. Mitochondrial porin, the voltage-dependent, anion-selective channel (VDAC), is responsible for the passage of small molecules between the mitochondrion and the cytosol. Through interactions with other mitochondrial and cellular proteins, it is involved in regu...
Article
Small multidrug resistance (SMR) protein family member, SugE, is an integral inner membrane protein that confers host resistance to antiseptic quaternary cation compounds (QCC). SugE studies generally focus on its resistance to limited substrates in comparison to SMR protein EmrE. This study examines the conformational characteristics of SugE prote...
Article
Escherichia coli multidrug resistance protein E (EmrE) is a four transmembrane alpha-helix protein, and a member of the small multidrug resistance protein family that confers resistance to a broad range of quaternary cation compounds (QCC) via proton motive force. The multimeric states of EmrE protein during transport or ligand binding are variable...
Article
EmrE and SugE are members of the small multidrug resistance protein family that can efflux quaternary cation compounds (QCC) via proton motive force within the Escherichia coli plasma membrane. Members of this integral membrane protein family are characterized by their short (∼100-140 amino acids) four transmembrane (TM) alpha- helix conformation a...
Article
Full-text available
The outer membrane of Gram-negative bacteria represents the interface between the bacterium and its external environment. It has a critical role as a protective barrier against harmful substances and is also important in host-bacteria interactions representing the initial physical point of contact between the host cell and bacterial cell. RopB is a...
Article
Full-text available
Mitochondrial porins (also known as voltage-dependent anion-selective channels (VDACs)) regulate and contribute to cellular metabolism. These proteins copurify with sterols, and some purified forms of the protein require sterol for insertion into planar artificial membranes. Recently, interactions between detergent-solubilized mitochondrial porins...
Data
Full-text available
A phylogenetic tree of the SMR protein family. The rooted phylogenetic tree is based on Neighbour-Joining analysis of 338 SMR protein sequences. The Archaeal Archaeoglobus QacE sequence served as an outgroup for this analysis. In some cases, individual PSMR sequences are highlighted by parenthesis and listed around branches to indicate important gr...
Data
An alignment of 338 SMR protein sequences identified from BLAST surveys of completed Archaeal and Bacterial genomes. The 338 SMR protein sequence alignment was truncated from a larger alignment of 685 SMR sequences that was generated using a manually edited ClustalW alignment. It is important to note that this alignment may contain truncated versio...
Data
Summary of synonymous to non-synonymous nucleotide substitution patterns within PSMR subclass members.
Article
Full-text available
Members of the small multidrug resistance (SMR) protein family are integral membrane proteins characterized by four alpha-helical transmembrane strands that confer resistance to a broad range of antiseptics and lipophilic quaternary ammonium compounds (QAC) in bacteria. Due to their short length and broad substrate profile, SMR proteins are suggest...
Article
Full-text available
Mitochondrial porins (voltage-dependent anion-selective channels, VDAC) are key contributors to cellular metabolism. When isolated from mitochondria porins copurify with sterols, and some isolated forms of the protein require sterol for insertion into artificial membranes. Nonetheless, the contributions of sterols to the folded state of mitochondri...
Article
Precise information regarding the transmembrane topology of mitochondrial porin is essential for understanding the mechanisms by which this protein functions. Porin acts as a channel in the outer membrane and interacts with small solutes and proteins to regulate mitochondrial function. The acquisition of high-resolution structural data requires a m...
Article
Full-text available
The small multidrug resistance (SMR) protein family is a bacterial multidrug transporter family. As suggested by their title, SMR proteins are composed of four transmembrane alpha-helices of approximately 100-140 amino acids in length. Since their designation as a family, many homologues have been identified and characterized both structurally and...
Data
Full-text available
Phylogenetic estimate of the evolutionary history of 244 porin amino acid sequences. The phylogenetic tree is based on a NJ majority rule consensus tree constructed by analysing 1000 bootstrap replicates. Levels of confidence for nodes are only given if bootstrap support exceeded 70%. The chordate VDAC1, VDAC2 and VDAC3 groupings are indicated; the...
Data
Mitochondrial porin sequence alignment in sequential (FASTA) format. The alignment of 244 mitochondrial porin sequences was obtained as described in Methods, and is presented in FASTA format. See [Additional File 1] for information regarding the source of individual sequences.
Data
Eukaryotic Porin Sequences. The table provides descriptions of the sequences used for the analysis, their sources, their designations in the datasets in [Additional Files 3 and 4], and the narrow classification of the organisms that were the sources of the indicated porin sequences.
Data
Mitochondrial porin sequence alignment in msf format. The alignment of 244 mitochondrial porin sequences was obtained as described in Methods, and is presented in msf format. See [Additional File 1] for information regarding the source of individual sequences.
Article
Full-text available
Mitochondrial porins, or voltage-dependent anion-selective channels (VDAC) allow the passage of small molecules across the mitochondrial outer membrane, and are involved in complex interactions regulating organellar and cellular metabolism. Numerous organisms possess multiple porin isoforms, and initial studies indicated an intriguing evolutionary...
Article
Mitochondrial porins are predicted to traverse the outer membrane as a series of beta-strands, but the precise structure of the resulting beta-barrel has remained elusive. Toward determining the positions of the membrane-spanning segments, a series of small deletions was introduced into several of the predicted beta-strands of the Neurospora crassa...
Article
Full-text available
Voltage-dependent anion-selective channels (VDAC), also known as mitochondrial porins, are key regulators of metabolite flow across the mitochondrial outer membrane. Porins from a wide variety of organisms share remarkably similar electrophysiological properties, in spite of considerable sequence dissimilarity, indicating that they share a common s...

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Projects

Projects (2)
Project
Identification of detergent systems for isolating folded native porin, and for achieving a similar folded state with recombinant porin isolated from fungal mitochondria.
Project
1. Bioinformatic analysis of qac gene distribution and co-association with other antimicrobial resistant genes. 2. Determine antimicrobial susceptibility profiles of qac members to various cationic antimicrobials 3. Identifying qac gene expression conditions by characterizing qac promoters