Hasan, Norshima Abu
(2019)
Elucidating The Mechanism Of Action
Of Caffeic Acid Phenethyl Ester (Cape)
Via Transcriptomic Profiling Of
Burkholderia Pseudomallei Strain K96243.
Masters thesis, Universiti Sains Malaysia.
Abstract
Burkholderia pseudomallei is a Gram-negative bacterial pathogen that causes
melioidosis, a life-threatening disease endemic in the regions of Southeast Asia,
particularly Malaysia and Thailand. B. pseudomallei is intrinsically resistant to wide
classes of clinically useful antibiotics, such as aminoglycosides, macrolides, β-lactams,
and older-generation cephalosporins. The expression of multiple efflux pumps and the
low permeability of the bacterium’s outer membrane contribute to its multidrug-resistant
(MDR) traits, which further complicate the therapeutic management for melioidosis.
Thus, a promising strategy to minimize the resistance level of MDR bacteria is by the use
of non-antibiotic helper compounds as an adjuvant to potentiate the antimicrobial activity
of antibiotics. In this study, the potential of caffeic acid and its derivatives, i.e. caffeic acid
phenethyl ester (CAPE), chlorogenic acid, and caffeic acid phenethyl amide (CAPA) to
act as antibiotic potentiators in B. pseudomallei were evaluated. We demonstrated that the
combination of a sub-inhibitory concentration of CAPE with gentamicin or kanamycin
significantly reduced the MIC of these antibiotics in B. pseudomallei by four-fold and
two-fold, respectively. Scanning electron microscopy further revealed that the fitness of
the cells treated with CAPE were compromised, with apparent phenotypic changes to the
cell morphology and disruption in the membrane architecture, such as shrunken, deformed
shape and formation of membrane blebs and dimples.
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