Targeting the Bacterial Cytoskeleton of the Burkholderia cepacia Complex for Antimicrobial Development: A Cautionary Tale

International Journal of Molecular Sciences
Sonya C CarnellAnthony De Soyza

Abstract

Burkholderia cepacia complex (BCC) bacteria are a group of opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult, due to the inherent and acquired multidrug resistance of BCC. There is a pressing need to find new bacterial targets for antimicrobials. Here, we demonstrate that the novel compound Q22, which is related to the bacterial cytoskeleton destabilising compound A22, can reduce the growth rate and inhibit growth of BCC bacteria. We further analysed the phenotypic effects of Q22 treatment on BCC virulence traits, to assess its feasibility as an antimicrobial. BCC bacteria were grown in the presence of Q22 with a broad phenotypic analysis, including resistance to H₂O₂-induced oxidative stress, changes in the inflammatory potential of cell surface components, and in-vivo drug toxicity studies. The influence of the Q22 treatment on inflammatory potential was measured by monitoring the cytokine responses of BCC whole cell lysates, purified lipopolysaccharide, and purified peptidoglycan extracted from bacterial cultures grown in the presence or absence of Q22 in differentiated THP-1 cells. BCC bacteria grown in the presence of Q22 displayed varying levels of ...Continue Reading

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Citations

Oct 12, 2018·International Journal of Molecular Sciences·Francesco Blasi
Oct 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Linda VáradiPaul W Groundwater
Jan 31, 2020·Frontiers in Chemistry·Elvis Awuni

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Methods Mentioned

BETA
electrophoretic profile
NMR
Protein Assay
electrophoresis
ELISA

Software Mentioned

Prism GraphPad

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