A. Tomljenovic-berube - Academia.edu (original) (raw)

Papers by A. Tomljenovic-berube

Research paper thumbnail of Thermosensing Coordinates a Cis-regulatory Module for Transcriptional Activation of the Intracellular Virulence System in Salmonella enterica Serovar Typhimurium

Journal of Biological Chemistry, Nov 1, 2007

The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity isla... more The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity island 2; LPM, low phosphate and magnesium; RIVET, recombinase-based in vivo expression technology; BAC, bacterial artificial chromosome.

Research paper thumbnail of Pathogenic adaptation of intracellular bacteria by rewiring a <i>cis</i> -regulatory input function

Proceedings of the National Academy of Sciences of the United States of America, Mar 10, 2009

Research paper thumbnail of Characterization of DalS, an ATP-binding Cassette Transporter for D-Alanine, and Its Role in Pathogenesis in Salmonella enterica

Journal of Biological Chemistry, 2012

Background: Bacterial pathogens must acquire nutrients for survival during host infection. Result... more Background: Bacterial pathogens must acquire nutrients for survival during host infection. Results: DalSTUV is an ABC transporter for D-alanine and contributes to virulence in vivo. Conclusion: Nutrient exchange during the host-pathogen interaction can direct disease outcome. Significance: This is the first report of an ABC transporter for D-alanine.

Research paper thumbnail of A New Dimension of Health Care: The Benefits, Limitations and Implications of Virtual Medicine

Journal of Undergraduate Life Sciences, 2021

Background: Virtual medicine has been rapidly evolving over the past several decades. However, ob... more Background: Virtual medicine has been rapidly evolving over the past several decades. However, obstacles such as data security, inadequate funding and limited technological resources have hindered its seamless incorporation into the health care system. The recent pandemic has induced a widespread adoption of virtual care practices to remove the need for physical meetings between patients and health care practitioners. Purpose: This literature review aims to examine the current state of virtual medicine amid the COVID-19 pandemic and evaluate the benefits, limitations and implications of continuing technological advancements in the future. Findings: Most of the available literature suggests that the recent adoption of virtual medicine has allowed practitioners to cut down on costs and secondary expenses while maintaining the quality of medical care services. Due to the growing consumer demand, researchers predict that virtual medicine may be a viable modality for patient care post-p...

Research paper thumbnail of Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis

Chemistry & Biology, 2009

The bacterial cell wall has been a celebrated target for antibiotics and holds real promise for t... more The bacterial cell wall has been a celebrated target for antibiotics and holds real promise for the discovery of new antibacterial chemical matter. In addition to peptidoglycan, the walls of Gram-positive bacteria contain large amounts of the polymer teichoic acid, covalently attached to peptidoglycan. Recently, wall teichoic acid was shown to be essential to the proper morphology of Bacillus subtilis and an important virulence factor for Staphylococcus aureus. Additionally, recent studies have shown that the dispensability of genes encoding teichoic acid biosynthetic enzymes is paradoxical and complex. Here, we report on the discovery of a promoter (P ywaC), which is sensitive to lesions in teichoic acid synthesis. Exploiting this promoter through a chemical-genetic approach, we revealed surprising interactions among undecaprenol, peptidoglycan, and teichoic acid biosynthesis that help explain the complexity of teichoic acid gene dispensability. Furthermore, the new reporter assay represents an exciting avenue for the discovery of antibacterial molecules.

Research paper thumbnail of Collaborative Writing

Critical Collaborative Communities, 2019

This chapter describes the collaborative writing experiences of a multidisciplinary group of educ... more This chapter describes the collaborative writing experiences of a multidisciplinary group of educators brought together through an International Collaborative Writing Group (ICWG) initiative originally organized by the International Society for the Scholarship of Teaching and Learning (ISSoTL) in 2012. Our ICWG writing partnership helped us develop our scholarship in ways that might not have otherwise been accomplished, had we worked alone or even with colleagues in our same institution or country. Through an analysis of a collection of individual reflective narratives about our collaborative writing experiences, we describe opportunities, affordances, inhibitors, and enablers for this approach to collaborative writing. We delineate the community of practice that we have successfully developed and how it has helped each of us develop our Scholarship of Teaching and Learning (SoTL). We share the mechanisms that we have used to facilitate our work; the types of choices we have made ab...

Research paper thumbnail of SsrB-dependent regulation during Salmonella pathogenesis

Bacteria demonstrate an extraordinary capacity to survive and adapt to changing environments. In ... more Bacteria demonstrate an extraordinary capacity to survive and adapt to changing environments. In part, this ability to adapt can be attributed to horizontal gene transfer, a phenomenon which introduces novel genetic information that can be appropriated for use in particular niches. Nowhere is this more relevant than in pathogenic bacteria, whose acquisition of virulence genes have provided an arsenal that permits them to thrive within their selected host. Regulatory evolution is necessary for timely regulation of these acquired virulence genes in the host environment. Salmonella enterica serovar Typhimurium is an intracellular pathogen which possesses numerous horizontallyacquired genomic islands encoding pathogenic determinants that facilitate its host lifestyle. One island, Salmonella Pathogenicity Island (SPI)-2, encodes a type-III secretion system (T3SS) which is regulated by the two-component regulatory system SsrA-SsrB. This system coordinates expression of the SPI-2 T3SS as well as an array of virulence effectors encoded in horizontally-acquired regions throughout the Salmonella genome. The studies presented here investigated the mechanisms in which the transcription factor SsrB functions to integrate virulence processes through regulatory adaptation. This work identified the regulatory logic controlling SsrB and defined the associated SsrB regulon. Furthermore, SsrB was found to induce a regulatory cascade responsible for the expression of bacteriophage genes encoded within SPI-12, an island that also contributes to Salmonella virulence. These findings demonstrate the important contribution of regulatory evolution in pathogen adaptation to the host, and show that vii TABLE OF CONTENTS

Research paper thumbnail of Research Approaches in Scholarship of Teaching and Learning Publications: A Systematic Literature Review

Teaching & Learning Inquiry, Sep 25, 2017

The Scholarship of Teaching and Learning (SoTL) has been described as the fastest growing academi... more The Scholarship of Teaching and Learning (SoTL) has been described as the fastest growing academic development movement in higher education. As this field of inquiry matures, there is a need to understand how SoTL research is conducted. The purpose of our study was to inform this debate by investigating research approaches used in SoTL publications. We analysed 223 empirical research studies published from 2012 to 2014 in three explicitlyfocused SoTL journals. We classified the studies as either qualitative, quantitative, or mixed methods using an analytical framework devised from existing literature on research methods. We found that the use of the three research designs was fairly evenly distributed across the papers examined: qualitative (37.2%), quantitative (29.6%), and mixed methods (33.2%). However, there was an over-reliance on data collection from a single source in 83.9% of papers analysed, and this source was primarily students. There was some, but limited, evidence of the use of triangulation through the use of multiple data collection instruments (e.g. survey, assessment tasks, grade databases). Similarly, only one-third of publications classified as mixed methods integrated the analysis and interpretation of the qualitative and quantitative data equally within the study. We conclude that current SoTL research is characterised by methodological pluralism but could be advanced through inclusion of more diverse approaches, such as close reading, and adoption of strategies known to enhance the quality of research, for example, triangulation and visual representation. KEYWORDS scholarship of teaching and learning, qualitative research, quantitative research, mixed methods, research approaches

Research paper thumbnail of Supplemental Data Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis

Research paper thumbnail of SoTL and Students' Experiences of their Degree-Level Programs: An Empirical Investigation

Teaching & Learning Inquiry: The ISSOTL Journal, 2013

Research paper thumbnail of Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function

Proceedings of the National Academy of Sciences, 2009

Research paper thumbnail of Thermosensing Coordinates a Cis-regulatory Module for Transcriptional Activation of the Intracellular Virulence System in Salmonella enterica Serovar Typhimurium

Journal of Biological Chemistry, 2007

The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity isla... more The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity island 2; LPM, low phosphate and magnesium; RIVET, recombinase-based in vivo expression technology; BAC, bacterial artificial chromosome.

Research paper thumbnail of Identification of the regulatory logic controlling Salmonella pathoadaptation by the SsrA-SsrB two-component system

Sequence data from the past decade has laid bare the significance of horizontal gene transfer in ... more Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrBdependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host.

Research paper thumbnail of Mapping and Regulation of Genes within Salmonella Pathogenicity Island 12 That Contribute to In Vivo Fitness of Salmonella enterica Serovar Typhimurium

Infection and Immunity, 2013

ABSTRACTSalmonellapathogenicity island 12 (SPI-12) ofSalmonella entericaserovar Typhimurium is a ... more ABSTRACTSalmonellapathogenicity island 12 (SPI-12) ofSalmonella entericaserovar Typhimurium is a 15-kb region that encompasses genesSTM2230toSTM2245and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for four genes in SPI-12 for bacterial survival in the host. STM2239, a potential Q antiterminator, showed a prominent contribution to bacterial fitness. Transcriptional reporter experiments, quantitative reverse transcription-PCR (RT-PCR), and immunoblotting demonstrated that the virulence regulator SsrB and STM2239 contribute to transcriptional activation of genes in SPI-12. SsrB was found to indirectly regulate this locus by transcriptional read-through from thesspH2(STM2241) promoter. Chromatin immunoprecipitation showed that STM2239 copurified with the promoter regulatingSTM2237, suggesting that STM2239 may function as an antiterminator to activate adjacent genes. These ...

Research paper thumbnail of Characterization of DalS, an ATP-binding Cassette Transporter for D-Alanine, and Its Role in Pathogenesis in Salmonella enterica

Journal of Biological Chemistry, 2012

Expansion into new host niches requires bacterial pathogens to adapt to changes in nutrient avail... more Expansion into new host niches requires bacterial pathogens to adapt to changes in nutrient availability and to evade an arsenal of host defenses. Horizontal acquisition of Salmonella Pathogenicity Island (SPI)-2 permitted the expansion of Salmonella enterica serovar Typhimurium into the intracellular environment of host cells by allowing it to deliver bacterial effector proteins across the phagosome membrane. This is facilitated by the SsrA-SsrB two-component regulatory system and a type III secretion system encoded within SPI-2. SPI-2 acquisition was followed by evolution of existing regulatory DNA, creating an expanded SsrB regulon involved in intracellular fitness and host infection. Here, we identified an SsrB-regulated operon comprising an ABC transporter in Salmonella. Biochemical and structural studies determined that the periplasmic solute-binding component, STM1633/DalS, transports D-alanine and that DalS is required for intracellular survival of the bacteria and for fitness in an animal host. This work exemplifies the role of nutrient exchange at the host-pathogen interface as a critical determinant of disease outcome.

Research paper thumbnail of Thermosensing Coordinates a Cis-regulatory Module for Transcriptional Activation of the Intracellular Virulence System in Salmonella enterica Serovar Typhimurium

Journal of Biological Chemistry, Nov 1, 2007

The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity isla... more The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity island 2; LPM, low phosphate and magnesium; RIVET, recombinase-based in vivo expression technology; BAC, bacterial artificial chromosome.

Research paper thumbnail of Pathogenic adaptation of intracellular bacteria by rewiring a <i>cis</i> -regulatory input function

Proceedings of the National Academy of Sciences of the United States of America, Mar 10, 2009

Research paper thumbnail of Characterization of DalS, an ATP-binding Cassette Transporter for D-Alanine, and Its Role in Pathogenesis in Salmonella enterica

Journal of Biological Chemistry, 2012

Background: Bacterial pathogens must acquire nutrients for survival during host infection. Result... more Background: Bacterial pathogens must acquire nutrients for survival during host infection. Results: DalSTUV is an ABC transporter for D-alanine and contributes to virulence in vivo. Conclusion: Nutrient exchange during the host-pathogen interaction can direct disease outcome. Significance: This is the first report of an ABC transporter for D-alanine.

Research paper thumbnail of A New Dimension of Health Care: The Benefits, Limitations and Implications of Virtual Medicine

Journal of Undergraduate Life Sciences, 2021

Background: Virtual medicine has been rapidly evolving over the past several decades. However, ob... more Background: Virtual medicine has been rapidly evolving over the past several decades. However, obstacles such as data security, inadequate funding and limited technological resources have hindered its seamless incorporation into the health care system. The recent pandemic has induced a widespread adoption of virtual care practices to remove the need for physical meetings between patients and health care practitioners. Purpose: This literature review aims to examine the current state of virtual medicine amid the COVID-19 pandemic and evaluate the benefits, limitations and implications of continuing technological advancements in the future. Findings: Most of the available literature suggests that the recent adoption of virtual medicine has allowed practitioners to cut down on costs and secondary expenses while maintaining the quality of medical care services. Due to the growing consumer demand, researchers predict that virtual medicine may be a viable modality for patient care post-p...

Research paper thumbnail of Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis

Chemistry & Biology, 2009

The bacterial cell wall has been a celebrated target for antibiotics and holds real promise for t... more The bacterial cell wall has been a celebrated target for antibiotics and holds real promise for the discovery of new antibacterial chemical matter. In addition to peptidoglycan, the walls of Gram-positive bacteria contain large amounts of the polymer teichoic acid, covalently attached to peptidoglycan. Recently, wall teichoic acid was shown to be essential to the proper morphology of Bacillus subtilis and an important virulence factor for Staphylococcus aureus. Additionally, recent studies have shown that the dispensability of genes encoding teichoic acid biosynthetic enzymes is paradoxical and complex. Here, we report on the discovery of a promoter (P ywaC), which is sensitive to lesions in teichoic acid synthesis. Exploiting this promoter through a chemical-genetic approach, we revealed surprising interactions among undecaprenol, peptidoglycan, and teichoic acid biosynthesis that help explain the complexity of teichoic acid gene dispensability. Furthermore, the new reporter assay represents an exciting avenue for the discovery of antibacterial molecules.

Research paper thumbnail of Collaborative Writing

Critical Collaborative Communities, 2019

This chapter describes the collaborative writing experiences of a multidisciplinary group of educ... more This chapter describes the collaborative writing experiences of a multidisciplinary group of educators brought together through an International Collaborative Writing Group (ICWG) initiative originally organized by the International Society for the Scholarship of Teaching and Learning (ISSoTL) in 2012. Our ICWG writing partnership helped us develop our scholarship in ways that might not have otherwise been accomplished, had we worked alone or even with colleagues in our same institution or country. Through an analysis of a collection of individual reflective narratives about our collaborative writing experiences, we describe opportunities, affordances, inhibitors, and enablers for this approach to collaborative writing. We delineate the community of practice that we have successfully developed and how it has helped each of us develop our Scholarship of Teaching and Learning (SoTL). We share the mechanisms that we have used to facilitate our work; the types of choices we have made ab...

Research paper thumbnail of SsrB-dependent regulation during Salmonella pathogenesis

Bacteria demonstrate an extraordinary capacity to survive and adapt to changing environments. In ... more Bacteria demonstrate an extraordinary capacity to survive and adapt to changing environments. In part, this ability to adapt can be attributed to horizontal gene transfer, a phenomenon which introduces novel genetic information that can be appropriated for use in particular niches. Nowhere is this more relevant than in pathogenic bacteria, whose acquisition of virulence genes have provided an arsenal that permits them to thrive within their selected host. Regulatory evolution is necessary for timely regulation of these acquired virulence genes in the host environment. Salmonella enterica serovar Typhimurium is an intracellular pathogen which possesses numerous horizontallyacquired genomic islands encoding pathogenic determinants that facilitate its host lifestyle. One island, Salmonella Pathogenicity Island (SPI)-2, encodes a type-III secretion system (T3SS) which is regulated by the two-component regulatory system SsrA-SsrB. This system coordinates expression of the SPI-2 T3SS as well as an array of virulence effectors encoded in horizontally-acquired regions throughout the Salmonella genome. The studies presented here investigated the mechanisms in which the transcription factor SsrB functions to integrate virulence processes through regulatory adaptation. This work identified the regulatory logic controlling SsrB and defined the associated SsrB regulon. Furthermore, SsrB was found to induce a regulatory cascade responsible for the expression of bacteriophage genes encoded within SPI-12, an island that also contributes to Salmonella virulence. These findings demonstrate the important contribution of regulatory evolution in pathogen adaptation to the host, and show that vii TABLE OF CONTENTS

Research paper thumbnail of Research Approaches in Scholarship of Teaching and Learning Publications: A Systematic Literature Review

Teaching & Learning Inquiry, Sep 25, 2017

The Scholarship of Teaching and Learning (SoTL) has been described as the fastest growing academi... more The Scholarship of Teaching and Learning (SoTL) has been described as the fastest growing academic development movement in higher education. As this field of inquiry matures, there is a need to understand how SoTL research is conducted. The purpose of our study was to inform this debate by investigating research approaches used in SoTL publications. We analysed 223 empirical research studies published from 2012 to 2014 in three explicitlyfocused SoTL journals. We classified the studies as either qualitative, quantitative, or mixed methods using an analytical framework devised from existing literature on research methods. We found that the use of the three research designs was fairly evenly distributed across the papers examined: qualitative (37.2%), quantitative (29.6%), and mixed methods (33.2%). However, there was an over-reliance on data collection from a single source in 83.9% of papers analysed, and this source was primarily students. There was some, but limited, evidence of the use of triangulation through the use of multiple data collection instruments (e.g. survey, assessment tasks, grade databases). Similarly, only one-third of publications classified as mixed methods integrated the analysis and interpretation of the qualitative and quantitative data equally within the study. We conclude that current SoTL research is characterised by methodological pluralism but could be advanced through inclusion of more diverse approaches, such as close reading, and adoption of strategies known to enhance the quality of research, for example, triangulation and visual representation. KEYWORDS scholarship of teaching and learning, qualitative research, quantitative research, mixed methods, research approaches

Research paper thumbnail of Supplemental Data Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis

Research paper thumbnail of SoTL and Students' Experiences of their Degree-Level Programs: An Empirical Investigation

Teaching & Learning Inquiry: The ISSOTL Journal, 2013

Research paper thumbnail of Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function

Proceedings of the National Academy of Sciences, 2009

Research paper thumbnail of Thermosensing Coordinates a Cis-regulatory Module for Transcriptional Activation of the Intracellular Virulence System in Salmonella enterica Serovar Typhimurium

Journal of Biological Chemistry, 2007

The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity isla... more The abbreviations used are: T3SS, type III secretion system; SPI-2, Salmonella pathogenicity island 2; LPM, low phosphate and magnesium; RIVET, recombinase-based in vivo expression technology; BAC, bacterial artificial chromosome.

Research paper thumbnail of Identification of the regulatory logic controlling Salmonella pathoadaptation by the SsrA-SsrB two-component system

Sequence data from the past decade has laid bare the significance of horizontal gene transfer in ... more Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrBdependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host.

Research paper thumbnail of Mapping and Regulation of Genes within Salmonella Pathogenicity Island 12 That Contribute to In Vivo Fitness of Salmonella enterica Serovar Typhimurium

Infection and Immunity, 2013

ABSTRACTSalmonellapathogenicity island 12 (SPI-12) ofSalmonella entericaserovar Typhimurium is a ... more ABSTRACTSalmonellapathogenicity island 12 (SPI-12) ofSalmonella entericaserovar Typhimurium is a 15-kb region that encompasses genesSTM2230toSTM2245and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for four genes in SPI-12 for bacterial survival in the host. STM2239, a potential Q antiterminator, showed a prominent contribution to bacterial fitness. Transcriptional reporter experiments, quantitative reverse transcription-PCR (RT-PCR), and immunoblotting demonstrated that the virulence regulator SsrB and STM2239 contribute to transcriptional activation of genes in SPI-12. SsrB was found to indirectly regulate this locus by transcriptional read-through from thesspH2(STM2241) promoter. Chromatin immunoprecipitation showed that STM2239 copurified with the promoter regulatingSTM2237, suggesting that STM2239 may function as an antiterminator to activate adjacent genes. These ...

Research paper thumbnail of Characterization of DalS, an ATP-binding Cassette Transporter for D-Alanine, and Its Role in Pathogenesis in Salmonella enterica

Journal of Biological Chemistry, 2012

Expansion into new host niches requires bacterial pathogens to adapt to changes in nutrient avail... more Expansion into new host niches requires bacterial pathogens to adapt to changes in nutrient availability and to evade an arsenal of host defenses. Horizontal acquisition of Salmonella Pathogenicity Island (SPI)-2 permitted the expansion of Salmonella enterica serovar Typhimurium into the intracellular environment of host cells by allowing it to deliver bacterial effector proteins across the phagosome membrane. This is facilitated by the SsrA-SsrB two-component regulatory system and a type III secretion system encoded within SPI-2. SPI-2 acquisition was followed by evolution of existing regulatory DNA, creating an expanded SsrB regulon involved in intracellular fitness and host infection. Here, we identified an SsrB-regulated operon comprising an ABC transporter in Salmonella. Biochemical and structural studies determined that the periplasmic solute-binding component, STM1633/DalS, transports D-alanine and that DalS is required for intracellular survival of the bacteria and for fitness in an animal host. This work exemplifies the role of nutrient exchange at the host-pathogen interface as a critical determinant of disease outcome.