Impact of a cross-kingdom signaling molecule of Candida albicans on Acinetobacter baumannii physiology

Xenia Kostoulias, Gerald L Murray, Gustavo C Cerqueira, Jason B Kong, Farkad Bantun, Eleftherios Mylonakis, Chen Ai Khoo, Anton Y Peleg

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Multidrug-resistant (MDR) Acinetobacter baumannii is an opportunistic human pathogen that has become highly problematic in the clinical environment. Novel therapies are desperately required. To assist in identifying new therapeutic targets, the antagonistic interactions between A. baumannii and the most common human fungal pathogen, Candida albicans, were studied. We have identified that the C. albicans quorum-sensing molecule, farnesol, has cross-kingdom interactions, affecting the viability of A. baumannii. To gain an understanding of its mechanism, the transcriptional profile of A. baumannii exposed to farnesol was examined. Farnesol caused dysregulation of a large number of genes involved in cell membrane biogenesis, multidrug efflux pumps (AcrAB-like, AdeIJK-like), and A. baumannii virulence traits such as biofilm formation (csuA, csuB, ompA) and motility (pilZ, pilH). We also observed a strong induction in genes involved in cell division (minD, minE, ftsK, ftsB, and ftsL). These transcriptional data were supported by functional assays, showing that farnesol disrupts A. baumannii cell membrane integrity, alters cell morphology, and impairs virulence characteristics such as biofilm formation and twitching motility. Moreover, we show that A. baumannii uses efflux pumps as a defence mechanism against this eukaryotic signalling molecule. Owing to its effects on membrane integrity, farnesol was tested to see if it potentiated the activity of the membrane-acting polymyxin antibiotic, colistin. When co-administered, farnesol increased sensitivity to colistin for otherwise resistant strains. These data provide mechanistic understanding into the antagonistic interactions between diverse pathogens and may provide important insights into novel therapeutic strategies.
Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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