Asunto(s)
Cadena Alimentaria , Rumiantes , Lobos , Animales , Cambio Climático , Endogamia , Michigan , PoblaciónRESUMEN
The dearth of new antibiotics in the face of widespread antimicrobial resistance makes developing innovative strategies for discovering new antibiotics critical for the future management of infectious disease. Understanding the genetics and evolution of antibiotic producers will help guide the discovery and bioengineering of novel antibiotics. We discovered an isolate in Alaskan boreal forest soil that had broad antimicrobial activity. We elucidated the corresponding antimicrobial natural products and sequenced the genome of this isolate, designated Streptomyces sp. 2AW. This strain illustrates the chemical virtuosity typical of the Streptomyces genus, producing cycloheximide as well as two other biosynthetically unrelated antibiotics, neutramycin, and hygromycin A. Combining bioinformatic and chemical analyses, we identified the gene clusters responsible for antibiotic production. Interestingly, 2AW appears dissimilar from other cycloheximide producers in that the gene encoding the polyketide synthase resides on a separate part of the chromosome from the genes responsible for tailoring cycloheximide-specific modifications. This gene arrangement and our phylogenetic analyses of the gene products suggest that 2AW holds an evolutionarily ancestral lineage of the cycloheximide pathway. Our analyses support the hypothesis that the 2AW glutaramide gene cluster is basal to the lineage wherein cycloheximide production diverged from other glutarimide antibiotics. This study illustrates the power of combining modern biochemical and genomic analyses to gain insight into the evolution of antibiotic-producing microorganisms.
Asunto(s)
Migración Animal , Lobos/fisiología , Animales , Animales Endogámicos , Ecosistema , Femenino , Cadena Alimentaria , Endogamia , Islas , Michigan , Población , Lobos/genéticaAsunto(s)
Extinción Biológica , Islas , Lobos , Animales , Cadena Alimentaria , Endogamia , Masculino , Michigan , Dinámica Poblacional , Lobos/anomalías , Lobos/crecimiento & desarrollo , Lobos/psicologíaRESUMEN
We have explored the microbial community in a nonpermafrost, cold Alaskan soil using both culture-based and culture-independent approaches. In the present study, we cultured >1000 bacterial isolates from this soil and characterized the collection of isolates phylogenetically and functionally. A screen for antibiosis identified an atypical, red-pigmented strain of Janthinobacterium lividum (strain BR01) that produced prodigiosin when grown at cool temperatures as well as strains (e.g., strain BP01) that are more typical of J. lividium, which produce a purple pigment, violacein. Both purple- and red-pigmented strains exhibited high levels of resistance to beta-lactam antibiotics. The prodigiosin pathway cloned from J. lividium BR01 was expressed in the heterologous host, Escherichia coli, and the responsible gene cluster differs from that of a well-studied prodigiosin producer, Serratia sp. J. lividum BR01 is the first example of a prodigiosin-producer among the beta-Proteobacteria. The results show that characterization of cultured organisms from previously unexplored environments can expand the current portrait of the microbial world.