Opportunistic bacteria, Burkholderia cepacia complex. Bacterial pathogenesis and microbial genomics. Antibacterial drug discovery.
Finding antibacterial targets and novel antibiotics.
The increase of antibiotic resistance in bacteria and the lack of novel antibacterial treatments are a great concern for public health. Our long-term goal is to find novel classes of antimicrobials and small molecules that are synergistic with antibiotics and to elucidate their mechanisms of action (MOA). As a model of multiple antibiotic resistant bacteria we use Burkholderia cenocepacia, which is a member of the Burkholderia cepacia complex (Bcc). People with the genetic disease cystic fibrosis are particularly susceptible to infections with Bcc.
We are developing a chemical genomic approach to antibiotic drug discovery that consists of small molecule screening with a genome-wide library of conditional growth mutants in essential genes. By studying mutant response at the genome level with next generation sequencing techniques we expect to find the MOA of novel small molecules with antibacterial activity.
Understanding growth in the host environment.
When bacteria cause infection they utilize host nutrients for growth. The type and availability of nutrients found by pathogenic bacteria can influence their virulence but the mechanisms are not always understood. Previous research in my laboratory identified the phenylalanine and phenylacetic acid degradation pathway as novel components required for full pathogenesis of B. cenocepacia in the host model Caenorhabditis elegans. We have discovered that interruption of this pathway causes release of phenylacetic acid which in turns inhibits the quorum sensing response. We propose that phenylacetic acid can act as a signal molecule that regulates virulence in microbial communities.
- Privitkova T, Lightly TJ, Kumar B, Bernier SP, Sorensen JL, Surette MG, Cardona S.T.. 2014. The attenuated virulence of a Burkholderia cenocepacia paaABCDE mutant is due to inhibition of quorum sensing by release of phenylacetic acid. Molecular Microbiology. 94:522-536
- Cardona S.T., Selin C, Gislason AS. Genomic tools to profile antibiotic mode of action. Crit Rev Microbiol. 2014 Mar 12. [Epub ahead of print] PubMed PMID: 24617440.
- Bloodworth, R. A. M., Gislason, A, Cardona, S.T. 2013. A Burkholderia cenocepacia Conditional Growth Mutant Library created by Random Promoter Replacement of Essential Genes. Microbiology Open 2:243-258.
- Kaplan, J., LoVetri, K., Cardona, S.T. , Madhyastha, S., Sadovskaya, I., Jabbouri, S., and Izano, E. 2012. Antibiofilm activity of recombinant human DNase I (Pulmozyme®) against Staphylococcus aureus and Staphylococcus epidermidis. The Journal of Antibiotics. 65:73-77.
- Imolhore I.A.I., Cardona, S.T., 2011. Three-hydroxyphenylacetic acid induces the Burkholderia cenocepacia phenylacetic acid degradation pathway - Towards understanding the contribution of aromatic catabolism. Frontiers in Cellular and Infection Microbiology 1.
- Yakandawala, N., Gawande, P., LoVetri, K., Cardona, S.T., Romeo, T., Nitz, M. and Madhyastha, S. 2011. Characterization of Poly-ß-1, 6-N-Acetylglucosamine Polysaccharide Component of Burkholderia Biofilms. Applied and Environmental Microbiology 77:8303-8309.
- Yudistira, H., McClarty, L., Hammond, S., Butcher, H., Mark, B. L. and Cardona S. T. 2011. Phenylalanine Induces Burkholderia cenocepacia Phenylacetic Acid Catabolism Through Degradation To Phenylacetyl-CoA In Synthetic Cystic Fibrosis Sputum Medium. Microbial Pathogenesis 52:183-193.
- Hamlin, J.N., Bloodworth, R.A.M., and Cardona, S.T. 2009. Regulation of phenylacetic acid degradation genes of Burkholderia cenocepacia K56-2. BMC Microbiology 8:222.
- Law, R. J., Hamlin, J. N., Sivro, A., McCorrister, S. J., Cardama, G. A., and Cardona, S. T. 2008. A functional phenylacetic acid catabolic pathway is required for full pathogenicity of Burkholderia cenocepacia in the Caenorhabditis elegans host model. Journal of Bacteriology 190: 7209-7218.
- Ortega, X. P., Cardona, S. T., Brown A. R., Loutet, S. A., Flannagan, R. S., Campoiano, D. J., Govan, J. R. W., and Valvano, M. A. 2007. A lipopolysaccharide modification gene cluster essential for viability in Burkholderia cenocepacia. Journal of Bacteriology 189:3639-3644.
- Cardona, S. T., Mueller C., and Valvano, M. A. 2006. Identification of essential operons in Burkholderia cenocepacia with a rhamnose inducible promoter. Applied and Environmental Microbiology 72:2547-2555.