Arousing sleeping genes: shifts in secondary metabolism of metal tolerant actinobacteria under conditions of heavy metal stress
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Numerous microbial habitats are strongly influenced by elevated levels of heavy metals. This type of habitat has developed either due to ore mining and metal processing or by pedogenesis above metal-rich base rocks. Most actinobacteria are soil-borne microbes with a remarkable capability for the synthesis of a broad variety of biologically active secondary metabolites. One major obstacle in identifying secondary metabolites, however, is the known phenomenon of sleeping gene clusters which are present, but silent under standard screening conditions. Here, we proceed to show that sleeping gene clusters can be awakened by the induction in heavy metal stress. Both, a chemical and a biological screening with extracts of supernatant and biomass of 10 strains derived from metal contaminated and non-contaminated environments was carried out to assay the influence of heavy metals on secondary metabolite patterns of metal tolerant actinobacteria. Metabolite patterns of cultures grown in complex and minimal media were compared to nickel (or cadmium) spiked parallels. Extracts of some strains grown in the presence of a metal salt displayed intense antibiosis against Escherichia coli, Mycobacterium smegmatis, Staphylococcus aureus and Candida albicans. Contrarily to the widely held opinion of metals as hindrance in secondary metabolism, metals thus can induce or enhance synthesis of possibly potent and medically relevant metabolites in metal tolerant strains. Hence, re-screening of existing strain libraries as well as identification of new strains from contaminated areas are valid strategies for the detection of new antibiotics in the future.
KeywordsActinobacteria Antibiosis Heavy metal Screening program Secondary metabolism
The authors are indebted to Christiane Weigel, Ulrike Valentin and Petra Mitscherlich for technical assistance.
- Hill DC, Wrigkey SK, Nisbet LJ (1998) Novel screen methodologies for identification of new microbial metabolites with pharmacological activity. Adv Biochem Eng Biotechnol 59:75–121Google Scholar
- Hopwood DA (2006) News feature: a call to arms. Nat Rev Drug Discov 6:8–12Google Scholar
- Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Preparation and analysis of genomic and plasmid DNA. In: Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (eds) Practical Streptomyces genetics. The John Innes Foundation, Norwich, pp 161–210Google Scholar
- Kruckeberg AR (1984) California serpentines flora, vegetation, geology, soils and management problems. University of California Press, Berkeley, Publications in Botany, vol 78, pp 1–180Google Scholar
- Lefèbvre C, Vernet P (1990) Microevolutionary processes on contaminated deposits. In: Shaw AJ (ed) Heavy metal tolerance in plants: evolutionary aspects. CRC Press, Boca Raton, pp 286–297Google Scholar
- Omura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M et al (2001) Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci USA 98:12215–12220. doi: 10.1073/pnas.211433198 PubMedCrossRefGoogle Scholar
- Sprocati AR, Alisi C, Segre L, Tasso F, Galletti M, Cremisini C (2006) Investigating heavy metal resistance, bioaccumulation and metabolic profile of a metallophile microbial consortium native to an abandoned mine. Sci Total Environ 366:649–658. doi: 10.1016/j.scitotenv.2006.01.025 PubMedCrossRefGoogle Scholar