Antifungals of acromyrmex, allomerus, and tetraponera ant- and cultivarassociated bacteria

The central purpose of this thesis is to test the utility of ant-microbe associations for discovering antifungal compounds with novel molecular (sub-) structures. Novel antifungals displaying reduced adverse side-effects, increased water-solubilities, and/or strong fungicidal properties would be helpful in medical science for responding to the rising prevalence of human mycoses and for solving problems with adverse side-effects in currently used antifungal drugs. Host-symbiont systems may represent a source of bacterial species that, due to their co-evolved association with hosts, have evolved antifungals differing in their molecular structures from antifungals of well-explored environmentalsources. To test the suitability of ant-microbe symbioses for discovering novel antifungals, I characterise ectosymbiotic bacteria and antifungal metabolites in three ant-associated niches: Acromyrmex octospinosus worker ants, fungal cultivars of Allomerus decemarticulatus and A. octoarticulatus, and Tetraponera penzigi worker ants and their putative fungal cultivar. I find that the A. octospinosus and T. penzigi niches hosted multiple bioactive actinobacteria including Streptomyces, Pseudonocardia, Nocardiopsis, and Saccharopolyspora. A Streptomyces strain from the Acromyrmex octospinosus niche was shown to produce the structurally unmodified antifungals candicidin and antimycin, which is suggestive of bacterial recruitment from environmental sources. Antimycin consisted of two sets of six molecules varying in number of attached CH2 groups. Both sets differ in polarity and fragmentation pattern. Only one set of antimycins inhibited the growth of Candida albicans, and this set revealed tandem-LCMS analogies with an antimycin A1-A4 standard. A Pseudonocardia strain from the same A. octospinosus niche was found to produce a partially novel (to science) and potentially water-soluble nystatinlike antifungal, which is suggestive of host-symbiont coevolution. These findings indicate that the host ant is able to use multiple-drug therapy in the form of antifungal �cocktails� to tackle resistance evolution in fungal pathogens. Overall, this research demonstrates that ant-microbe associations provide new opportunities for finding abundant bioactive bacteria and novel antibiotics.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2013

Author dc:creator

• Barke, Joerg

Language dc:language

en