Polyenic Antibiotics and Other Antifungal Compounds Produced by Hemolytic Streptomyces Species

Abstract

Streptomyces are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic Streptomyces isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated S. sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of Streptomyces to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by Streptomyces is presented.

Keywords: Actinomycetales; Streptomyces; hemolysis; polyene antibiotics; secondary metabolites; soil ecosystem; symbiosis.

Figure 2

Hemolytic activity of supernatants after proteinase K treatment or boiling. Cell-free supernatants from 72-h-old cultures of strains BCCO 10_1331, BCCO 10_2259, BCCO 10_2295, BCCO 10_2309 (listed from left) were treated by proteinase K (upper discs on each plate) or were boiled (discs on the left of each plate), or no additional treatment have been performed (control discs on the right side of each plate).

Figure 1

Phylogeny of Streptomyces strains involved in the study inferred from 16S rRNA gene similarity. Color codes represent the type of a polyene produced by the strain, the isolation source, and the country of origin. Only bootstraps above 50 are shown. The question mark indicates metabolites detected in a co-culture. The sequences of type strains closely related to the sequences of known polyene producers and BCCO strains were included to support topography of phylogenetic tree. The strains were selected according to Labeda et al. [96]. Abbreviations: A.–Amycolatopsis, N.–Nocardioides, S.–Streptomycces.