Influence of Chelation Strength and Bacterial Uptake of Gallium Salicylidene Acylhydrazide on Biofilm Formation and Virulence by Pseudomonas aeruginosa
2016 (English)In: Journal of Inorganic Biochemistry, ISSN 0162-0134, E-ISSN 1873-3344, Vol. 160, 24-32 p.Article in journal (Refereed) Published
Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on bacterial cells. This was investigated by comparing Ga chelation strength of two hydrazone complexes, as well as bacterial Ga uptake, biofilm formation, and virulence in the form of production and secretion of a toxin (ExoS) by Pseudomonas aeruginosa. Equilibrium constants for deprotonation and Ga(III) binding of the hydrazone N′-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide (ME0329), with anti-virulence effect against P. aeruginosa, were determined and compared to bacterial siderophores and the previously described Ga(III) 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (Ga-ME0163) and Ga-citrate complexes. In comparison with these two complexes, it was shown that the uptake of Ga(III) was higher from the Ga-ME0329 complex. The results further show that the Ga-ME0329 complex reduced ExoS expression and secretion to a higher extent than Ga-citrate, Ga-ME0163 or the non-coordinated hydrazone. However, the effect against biofilm formation by P. aeruginosa, by the ME0329 complex, was similar to Ga-citrate and lower than what has been reported for Ga-ME0163.
Place, publisher, year, edition, pages
Elsevier, 2016. Vol. 160, 24-32 p.
Gallium, Equilibrium constants, Virulence, Biofilm, Bacteria, UV–vis
Chemical Sciences Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:umu:diva-107749DOI: 10.1016/j.jinorgbio.2016.04.010ISI: 000378965200003PubMedID: 27118030OAI: oai:DiVA.org:umu-107749DiVA: diva2:849356
FunderSwedish Research Council, 2011-3504Swedish Research Council, 2012-2976