Silvia T Cardona

Silvia T Cardona
University of Manitoba | UMN · Department of Microbiology

PhD. Microbiology

About

87
Publications
6,740
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1,243
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Introduction
Silvia T Cardona is a Professor in the Department of Microbiology, University of Manitoba. Silvia does research in Molecular Microbiology and Microbial Genomics. Current projects in the Cardona lab are: 1) Machine learning approaches to antibiotic discovery 2) Investigation of new antimicrobials' mechanisms of action 3) Development of green antimicrobials 4) Synthetic biology methods for biotechnological applications 5) Links between metabolism and virulence
Additional affiliations
January 2013 - present
University of Manitoba
Position
  • Professor (Associate)
July 2012 - present
University of Manitoba
Position
  • Professor (Associate)
April 2006 - July 2012
University of Manitoba
Position
  • Professor (Assistant)

Publications

Publications (87)
Article
Detection of antibiotic compounds in various media is necessary in solving the public health crisis of antibiotic resistance[1]. Auranofin (AF) is a repurposed antibiotic first used as an antirheumatic in the 1950s. It is useful against various bacteria, fungi, virus infections and cancers either by itself or synergistically with other antibiotics[...
Article
Full-text available
Acinetobacter baumannii causes a wide range of infections that are difficult to treat due to increasing rates of multidrug resistance; however, the mechanisms that this pathogen uses to respond to stress are poorly understood. Here, we describe a new mechanism of stress signaling in Acinetobacter that is mediated by the metabolite phenylacetic acid...
Article
Full-text available
Background Converting molecules into computer-interpretable features with rich molecular information is a core problem of data-driven machine learning applications in chemical and drug-related tasks. Generally speaking, there are global and local features to represent a given molecule. As most algorithms have been developed based on one type of fea...
Article
Full-text available
Motivation Chemical–genetic interaction profiling is a genetic approach that quantifies the susceptibility of a set of mutants depleted in specific gene product(s) to a set of chemical compounds. With the recent advances in artificial intelligence, chemical–genetic interaction profiles (CGIPs) can be leveraged to predict mechanism of action of comp...
Article
Essential genes encode the processes that are necessary for life. Until recently, commonly applied binary classifications left no space between essential and non-essential genes. In this review, we frame bacterial gene essentiality in the context of genetic networks. We explore how the quantitative properties of gene essentiality are influenced by...
Article
Full-text available
A first clue to gene function can be obtained by examining whether a gene is required for life in certain standard conditions, that is, whether a gene is essential. In bacteria, essential genes are usually identified by high-density transposon mutagenesis followed by sequencing of insertion sites (Tn-seq). These studies assign the term “essential”...
Article
Electrochemical sensors are gaining attention for the detection and quantification of pharmaceuticals in the environment. To that end, there is an interest in understanding the electrochemical characteristics of drugs. Herein, the multi‐purpose drug auranofin is investigated for the first time in aqueous media. This compound offers therapeutic bene...
Article
Full-text available
Bacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated w...
Preprint
Full-text available
Bacteria of the genus Burkholderia includes pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated...
Article
A diverse genetic toolkit is critical for understanding bacterial physiology and genotype-phenotype relationships. Inducible promoter systems are an integral part of this toolkit. In Burkholderia and related species, the L-rhamnose-inducible promoter is among the first choices due to its tight control and the lack of viable alternatives. To improve...
Preprint
Full-text available
A first clue to gene function can be obtained by examining whether a gene is required for life in certain standard conditions, that is, whether a gene is essential. In bacteria, essential genes are usually identified by high-density transposon mutagenesis followed by sequencing of insertion sites (Tn-seq). These studies assign the term “essential”...
Article
Staphylococcus aureus chronic airway infection in patients with cystic fibrosis (CF) allows this pathogen to adapt over time in response to different selection pressures. We have previously shown that the main sequence types related to community-acquired methicillin-resistant S. aureus (MRSA) infections in Argentina – ST5 and ST30 – are also freque...
Article
Full-text available
The opportunistic pathogen Burkholderia cenocepacia uses a chemical signal process called quorum sensing (QS) to produce virulence factors. In B. cenocepacia , QS relies on the presence of the transcriptional regulator CepR which, upon binding QS signal molecules, activates virulence. In this work, we found that even in the absence of CepR, B. ceno...
Article
Full-text available
Bacteria of the Burkholderia cepacia complex (Bcc) are associated with significant decline of lung functions in cystic fibrosis patients. Bcc infections are virtually impossible to eradicate due to their irresponsiveness to antibiotics. The 2-thiocyanatopyridine derivative 11026103 is a novel, synthetic compound active against Burkholderia cenocepa...
Article
Genetic tools are critical to dissecting the mechanisms governing cellular processes, from fundamental physiology to pathogenesis. Members of the genus Burkholderia have potential for biotechnological applications but can also cause disease in humans with a debilitated immune system. The lack of suitable genetic tools to edit Burkholderia GC-rich g...
Preprint
Full-text available
During phenylalanine catabolism, phenylacetic acid (PAA) is converted to phenylacetyl-CoA (PAA-CoA) by a ligase, PaaK, and then epoxidized by a multicomponent monooxygenase, PaaABCDE, before further degradation to the TCA cycle. In the opportunistic pathogen Burkholderia cenocepacia, loss of paaABCDE attenuates virulence factor expression, which is...
Preprint
Full-text available
Genetic tools are critical to dissecting the mechanisms governing cellular processes, from fundamental physiology to pathogenesis. Members of the genus Burkholderia have potential for biotechnological applications but can also cause disease in humans with a debilitated immune system. The lack of suitable genetic tools to edit Burkholderia GC-rich g...
Article
The rise in antibiotic resistance among pathogenic microorganisms has created an imbalance in the drugs available for treatment, in part due to the slow development of new antibiotics. Cystic fibrosis (CF) patients are highly susceptible to antibiotic-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Phloroglucinols...
Article
Full-text available
To streamline elucidation of antibacterial compounds’ mechanism of action, comprehensive high-throughput assays interrogating multiple putative targets are necessary. However, current chemogenomic approaches for antibiotic target identification have not fully utilized the multiplexing potential of next-generation sequencing. Here, we used Illumina...
Article
Full-text available
Burkholderia cenocepacia is an opportunistic bacterium that can thrive in different environments, including the amino acid-rich mucus of the cystic fibrosis (CF) lung.B. cenocepaciaresponds to the nutritional conditions that mimic the CF sputum by increasing flagellin expression and swimming motility. Individual amino acids also induce swimming but...
Article
Full-text available
Novel therapies are urgently needed to alleviate the current crisis of multiple drug-resistant infections. The bacterial signal transduction mechanisms, known as two-component systems (TCSs), are ideal targets of novel inhibitory molecules. Highly restricted to the bacterial world, TCSs control a diverse set of cellular functions, namely virulence,...
Article
Full-text available
Burkholderia cenocepacia K56-2 belongs to the Burkholderia cepacia complex, a group of Gram-negative opportunistic pathogens that have large and dynamic genomes. In this work, we identified the essential genome of B. cenocepacia K56-2 using high-density transposon mutagenesis and insertion site sequencing (Tn-seq circle). We constructed a library o...
Article
There are hundreds of essential genes in multidrug resistant bacterial genomes, but only a few of their products are exploited as antibacterial targets. An example is the electron flavoprotein (ETF) which is required for growth and viability in Burkholderia cenocepacia . Here, we evaluated ETF as an antibiotic target for Burkholderia cepacia comple...
Article
Phenylacetic acid (PAA), an intermediate of phenylalanine degradation, is emerging as a signal molecule in microbial interactions with the host. In this work, we explore the presence of phenylalanine and PAA catabolism in three microbial pathogens of the cystic fibrosis (CF) lung microbiome: Pseudomonas aeruginosa , Burkholderia cenocepacia and Asp...
Article
Chemogenetic approaches to profile antibiotic mode of action are based on detecting differential sensitivity of engineered bacterial strains in which the antibacterial target (usually encoded by an essential gene) or an associated process are regulated. We previously developed an essential gene-knockdown mutant library in the multidrug resistant Bu...
Article
Burkholderia contaminans is a species of the Burkholderia cepacia complex, a group of bacteria that can grow in pharmaceutical products and are capable of infecting the immunocompromised and people with cystic fibrosis. Here, we report draft genome sequences for Burkholderia contaminans FFI-28, a strain isolated from a contaminated pharmaceutical s...
Article
Full-text available
Several bacterial species from the Burkholderia cepacia complex (Bcc) are feared opportunistic pathogens that lead to debilitating lung infections with a high risk of developing fatal septicemia in cystic fibrosis (CF) patients. However, the pathogenic potential of other Bcc species is yet unknown. To elucidate clinical relevance of Burkholderia co...
Data
Genes exhibiting differential expression between B. contaminans isolates 467_S and MF16_B (> 3-fold change, p < 0.05), not included in Table 2, S2, S3 and S4 Tables. (DOCX)
Data
Variants detected by mapping Illumina sequencing reads (isolates MF16_B and FFH2055) on PacBio reference assembly of FFH2055 (contigs NZ_LASC01000001.1 to NZ_LASC01000008.1). Nucleotide sequence and reading frame of affected genes was assessed by comparison with homologues in B. contaminans MS14 genome. (XLSX)
Data
Antifungal compound biosynthetic clusters with differential expression between B. contaminans isolates 467_S and MF16_B (> 3-fold change, p < 0.05). (DOCX)
Data
List of the genomic differences between B. contaminans ST872 isolates 467_S and MF16_B. Differences were detected by mapping Illumina reads of 467_S on the FFH2055 reference assembly and subtracting variants present also in MF16_B. The mutations are denoted in the direction MF16_B → 467_S. (XLSX)
Data
QS regulators and QS-regulated virulence genes with differential expression between B. contaminans isolates 467_S and MF16_B (> 3-fold change, p < 0.05). (DOCX)
Data
Motility and chemotaxis genes exhibiting differential expression between B. contaminans isolates 467_S and MF16_B (> 3-fold change, p < 0.05). (DOCX)
Article
Full-text available
Burkholderia cenocepacia belongs to the Burkholderia cepacia complex (Bcc), a group of at least 18 distinct species that establish chronic infections in the lung of people with the genetic disease cystic fibrosis (CF). The sputum of CF patients is rich in amino acids and was previously shown to increase flagellar gene expression in B. cenocepacia....
Data
Primers used in this study.
Data
TEM images of B. cenocepacia K56-2 WT. (A,B) Multiple flagella present on WT strain cell surface in CF nutritional conditions. (C,D) Single and multiple polar flagella in MOPS-glucose 20 mM.
Data
Bright-field microscopic images of B. cenocepacia K56-2 WT stained flagella: The bacterial flagella were stained using Remel flagella dye. (A) Stained multiple flagellated WT strain cells in CF nutritional conditions. (B) Stained polar flagellum or aflagellated cells in MOPS-glucose 20 mM. Scale bars represent 2 μm in all images.
Data
Individual amino acids as a sole carbon source: Growth and motility of the B. cenocepacia K56-2 WT was examined in MOPS containing 5 mM amino acids as individual carbon sources. The symbols “++,” “+,” and “−” represent high, moderate and no growth or motility respectively.
Article
Full-text available
Burkholderia contaminans belongs to the Burkholderia cepacia complex (BCC), a group of bacteria that are ubiquitous in the environment and capable of infecting the immunocompromised and people with cystic fibrosis. We report here draft genome sequences for the B. contaminans type strain LMG 23361 and an Argentinian cystic fibrosis sputum isolate. C...
Article
Essential gene studies often reveal novel essential functions for genes with dispensable homologs in other species. This is the case with the widespread family of electron transfer flavoproteins (ETFs), which are required for the metabolism of specific substrates or for symbiotic nitrogen fixation in some bacteria. Despite these non-essential funct...
Article
Full-text available
Infections with the bacteria Burkholderia cepacia complex (Bcc) are very difficult to eradicate in cystic fibrosis patients due the intrinsic resistance of Bcc to most available antibiotics and the emergence of multiple antibiotic resistant strains during antibiotic treatment. In this work, we used a whole-cell based assay to screen a diverse colle...
Article
Full-text available
The development of antibacterial compounds that perturb novel processes is an imperative in the challenge presented by widespread antibiotic resistance. While many antibiotics target the ribosome, molecules that inhibit ribosome assembly have yet to be used in this manner. Here we show that a novel inhibitor of ribosome biogenesis, lamotrigine, is...
Conference Paper
Burkholderia cenocepacia is an opportunistic pathogen, member of Burkholderia cepacia complex (Bcc), which has been identified from cystic fibrosis (CF) patients. Its large genome is comprised of three chromosomes, which increases its genomic diversity and occurrence in various environmental niches. CF isolates of Bcc strains are intrinsically resi...
Article
The phenylacetic acid degradation pathway of Burkholderia cenocepacia is active during cystic fibrosis-like conditions and is necessary for full pathogenicity of B. cenocepacia in nematode and rat infection models; however, the reasons for such requirements are unknown. Here, we show that the attenuated virulence of a phenylacetic acid catabolism m...
Article
Abstract The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and...
Article
Full-text available
Identification of essential genes by construction of conditional knockouts with inducible promoters allows the identification of essential genes and creation of conditional growth (CG) mutants that are then available as genetic tools for further studies. We used large-scale transposon delivery of the rhamnose-inducible promoter, PrhaB followed by r...
Article
Full-text available
The phenylacetic acid (PA) degradative pathway is the central pathway by which various aromatic compounds (e.g., styrene) are degraded. Upper pathways for different aromatic compounds converge at common intermediate phenylacetyl-CoA (PA-CoA), which is then metabolized to succinyl-CoA and acetyl-CoA. We previously made a link in Burkholderia cenocep...
Article
Full-text available
Extracellular DNA is an adhesive component of staphylococcal biofilms. The aim of this study was to evaluate the antibiofilm activity of recombinant human DNase I (rhDNase) against Staphylococcus aureus and Staphylococcus epidermidis. Using a 96-well microtiter plate crystal-violet binding assay, we found that biofilm formation by S. aureus was eff...
Article
Full-text available
We demonstrated the production of poly-β-1,6-N-acetylglucosamine (PNAG) polysaccharide in the biofilms of Burkholderia multivorans, Burkholderia vietnamiensis, Burkholderia ambifaria, Burkholderia cepacia, and Burkholderia cenocepacia using an immunoblot assay for PNAG. These results were confirmed by further studies, which showed that the PNAG hyd...
Article
Full-text available
Metabolically versatile soil bacteria Burkholderia cepacia complex (Bcc) have emerged as opportunistic pathogens, especially of cystic fibrosis (CF). Previously, we initiated the characterization of the phenylacetic acid (PA) degradation pathway in B. cenocepacia, a member of the Bcc, and demonstrated the necessity of a functional PA catabolic path...
Data
Position Weight Matrix Calculations. A) The sequences used to generate the matrix of the conserved inverted repeat from the paaA, paaH, paaZ, paaF and BCAL0211 genes. B) The sum the occurrence of nucleotides at each position. C) The formulas used to generate the PWM, modified from [25] p(b, i) = corrected probability of base b in position i; f(b, i...
Data
Position Weight Matrix scores in a genomic scan of B. cenocepacia. The position weight matrix calculated in Additional file 2 was used to scan the genome of Burkholderia cenocepacia K56-2. Genome co-ordinate is from the annotated sequence [4].