Browsing by Author "Jervis, Nicole Marie"

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    The effects of diketopiperazines on the virulence of Burkholderia cepacia complex species
    (2021-01-15) Jervis, Nicole Marie; Storey, Douglas G.; Harrison, Joe J.; Parkins, Michael D.; Savchenko, Alexei; Storey, Douglas G.
    Recognized as a novel class of quorum sensing inhibitors (QSIs), 2,5-diketopiperazines (DKPs) are small, organic molecules that hold many important physiochemical properties which has led to recent inquiries into their effects towards limiting the pathogenicity of multi-drug resistant bacterial pathogens. Species within the Burkholderia cepacia complex (Bcc) are one such group of pathogens that require attention towards the development of alternative therapeutic strategies given their detrimental clinical outcomes, particularly in patients with cystic fibrosis. By targeting Bcc QS regulation, our data demonstrated DKPs, cyclo(-D-ala-val), cyclo(-pro-val), cyclo(-leu-pro), and cyclo(-phe-pro) to alter the production of extracellular virulence factors and to decrease the production of biofilm-associated factors which comprise the protective extracellular matrix of Bcc biofilms. Further analysis demonstrated these DKPs to also possess antibiotic potentiator activity, enhancing the antimicrobial activity of ceftazidime, meropenem, and tobramycin. Taken together, the data collected in this study offers an initial step towards understanding the potential role of DKPs in the development of alternative therapeutics.