Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation

Abstract

Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF₃), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF₃, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.

Graphical Abstract

Keywords:

• Chalcones
• antibiofilm
• OmpA
• dual-species biofilm
• Acinetobacter baumannii
• Candida

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia [Grant No. 451-03-68/2022-14/200042 and 451-03-68/2022-14/200161].