Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals
Author:
Montaño Elizabeth T.ORCID, Nideffer Jason F., Brumage Lauren, Erb Marcella, Busch Julia, Fernandez LynleyORCID, Derman Alan I., Davis John Paul, Estrada Elena, Fu Sharon, Le Danielle, Vuppala Aishwarya, Tran Cassidy, Luterstein Elaine, Lakkaraju Shivani, Panchagnula SriyaORCID, Ren Caroline, Doan Jennifer, Tran Sharon, Soriano Jamielyn, Fujita YuyaORCID, Gutala Pranathi, Fujii Quinn, Lee Minda, Bui AnthonyORCID, Villarreal CarleenORCID, Shing Samuel R., Kim SeanORCID, Freeman Danielle, Racha Vipula, Ho Alicia, Kumar Prianka, Falah Kian, Dawson Thomas, Enustun Eray, Prichard Amy, Gomez Ana, Khanna KanikaORCID, Trigg ShellyORCID, Pogliano Kit, Pogliano JoeORCID
Abstract
The threat to public health posed by drug-resistant bacteria is rapidly increasing, as some of healthcare’s most potent antibiotics are becoming obsolete. Approximately two-thirds of the world’s antibiotics are derived from natural products produced by Streptomyces encoded biosynthetic gene clusters. Thus, to identify novel gene clusters, we sequenced the genomes of four bioactive Streptomyces strains isolated from the soil in San Diego County and used Bacterial Cytological Profiling adapted for agar plate culturing in order to examine the mechanisms of bacterial inhibition exhibited by these strains. In the four strains, we identified 104 biosynthetic gene clusters. Some of these clusters were predicted to produce previously studied antibiotics; however, the known mechanisms of these molecules could not fully account for the antibacterial activity exhibited by the strains, suggesting that novel clusters might encode antibiotics. When assessed for their ability to inhibit the growth of clinically isolated pathogens, three Streptomyces strains demonstrated activity against methicillin-resistant Staphylococcus aureus. Additionally, due to the utility of bacteriophages for genetically manipulating bacterial strains via transduction, we also isolated four new phages (BartholomewSD, IceWarrior, Shawty, and TrvxScott) against S. platensis. A genomic analysis of our phages revealed nearly 200 uncharacterized proteins, including a new site-specific serine integrase that could prove to be a useful genetic tool. Sequence analysis of the Streptomyces strains identified CRISPR-Cas systems and specific spacer sequences that allowed us to predict phage host ranges. Ultimately, this study identified Streptomyces strains with the potential to produce novel chemical matter as well as integrase-encoding phages that could potentially be used to manipulate these strains.
Funder
National Institutes of Health
Publisher
Public Library of Science (PLoS)
Subject
Multidisciplinary
Cited by
4 articles.
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