Streptomyces filamentosus
1. Classification
a. Higher order taxa
Domain: Bacteria Phylum: Actinomycetota Class: Actinomycetes Order: Kitasatosporales Family: Streptomycetaceae Genus: Streptomyces Species: S. filamentosus[1]
2. Introduction
Streptomyces filamentosus (also known as Streptomyces roseosporus) is a bacterial species that belongs to the phyla Actinobacteria and the order Actinomycetales [2]. S. filamentosus is a gram-positive, aerobic bacterium that forms spores [3]. S. filamentosus produces daptomycin, a cyclic lipopeptide antibiotic that works against Gram-positive and Gram-negative bacteria [4]; it was approved to treat skin infections by the FDA in 2003 [5]. It is not fully known how to increase daptomycin production and efficiency in S. filamentosus, or whether it produces molecules capable of other antibiotic, antifungal, and antiviral properties [2]. =3. Organism
a. Genome structure
S. filamentosus has a genome of 7.9Mb with 73.5% of the genome being guanine and cytosine. 96.5% of the genes in the genome are protein encoding [6]. The bacterial genome is also characterized by the presence of linear and mega plasmids. The genes responsible for secondary metabolite production are found to be in clusters on the chromosome and in some cases on the linear plasmid [7]. S. filamentosus encodes a variety of stress proteins, specifically temperature shock proteins from the CspA family (cold shock) and the heat shock protein 60 family. It also encodes alkaline shock protein 23, arsenic resistance protein ACR3, and penicillin binding proteins [7].
b. Cell structure
S. filamentosus is a Gram-positive, non-motile [8] bacteria that grows as branching hyphal filaments of mycelium when there is a large supply of nutrients, but otherwise remain in a semi-dormant state for most of its life cycle ([7]. The bacteria reproduce by branches moving upwards in straight spore chains made up of rod-like spores, similar to fungi, and do so rapidly when there is a large supply of nutrients [2].
c. Metabolic processes
S. filamentosus are aerobic or facultative anaerobic bacteria [2]. It is part of the Actinomycetes class, meaning it is a synthesizer of antibiotics (secondary metabolites), specifically daptomycin. Daptomycin is effective against Gram-negative and positive bacteria, as well as fungi. Due to rising antibiotic resistance amongst microbes, daptomycin is gaining popularity as a substitute for vancomycin and methicillin [4]. Some microbes daptomycin works against are B. subtilis, S. flexneri, E. coli, B. cereus, and E. faecalis [2]. The secretion of antibiotics by S. filamentosus coincides with the reproductive phase of the bacteria [4] and is greatly influenced by the availability of oxygen [3].
d. Ecology
S. filamentosus is found in soil environments, majorly in terrestrial environments such as in the Great Salt Plains of Oklahoma [7], but also found in marine sediment [2]. S. filamentosus can live in psychrophilic and mesophilic conditions. They are able to withstand soil with high salt concentration (ranging from 0.1% to 30% salinity) and a wide range of temperatures (subzero to 45C). S. filamentosus in high temperature environments act as composters [7].
e. Pathology
While some species from the Streptomyces genus are pathogenic in humans and plants, S. filametosus has not been found to be pathogenic [9].
4. Current Research
Current research involves characterizing Streptomyces filamentosus to address the growing challenges of antimicrobial resistance [2]. A recent profiling of S. filamentosus strain K17 from Devbag beach, India, revealed robust antimicrobial activity. Approximately 30 bioactive compounds with antibacterial and anticancer properties were detected, suggesting that S. filamentosus could be a promising candidate for the development of antimicrobial drugs [2]. Further research on the purification, characterization of the antibiotic compounds, and description of their biosynthetic gene clusters is needed to confirm the properties of these bioactive compounds.
Experiments with mutations are currently being conducted due to antibiotic resistance in S. filamentosus to test whether these mutations increase daptomycin production. In a study done in 2012, plasmid sequences responsible for daptomycin production in S. filamentosus were created via PCR, and subjected to streptomycin, which inhibits protein synthesis. A resulting mutant with on lysine 43 mutated to asparagine caused daptomycin production to increase by 2.2 fold [10]. In a following study in 2013, S. filamentosus was subjected to pleuromutilin, which targets the bacterial ribosomes. This time, a mutation in codon 455, substituting glycine with valine caused daptomycin production to increase by 30 percent [11]. Genetic engineering via antibiotic induced mutations could be useful in the future, but need to be studied more as the mutations are slow to occur and not fully understood.
Researchers have recently attempted to develop strains with increased daptomycin production, fewer byproducts, and higher environmental resistance. Due to the wild-type strain’s low production of daptomycin and various undesirable by-products, new mutant strains were created through the use of UV radiation and NTG mutagenesis. After repeated generations of mutation, the DKB108 S. filamentous strain was obtained which had 12 times more daptomycin production compared to the parent strain ATCC 31568 [12]. Additionally, this strain was capable of surviving higher sodium chloride levels and had a wider carbon usage than its parent strain. In a recent breakthrough, the CRISPR-Cas9 gene cluster activation strategy was employed on S. filamentosus to synthesize a new antibiotic called auroramycin [13]verified using various methods to ensure construction accuracy [13]. The activated gene cluster was also validated through analyses and gene deletions. Auroramycin demonstrated antimicrobial efficacy against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Its effectiveness closely resembles that of vancomycin when tested against two clinical drug resistant MRSA isolates, including one identified as a vancomycin-intermediate (VI-MRSA) strain that also exhibits resistance to daptomycin [13]. The discovery of this potent antibiotic could provide an alternative to current antibiotics. In addition to having antimicrobial properties, strains of S. filamentosus have also been found to be useful in treating soil. An aerobic strain of S. filamentosus, designated ES2-5, was isolated from selenium mining soil in southwest China [14]. Analysis revealed its ability to reduce selenium under aerobic conditions. Due to its spore production, selenium reduction capabilities, and adaptation to soil conditions, this strain holds potential for selenium bioremediation in contaminated soil [14].
5. References
[1][U.S. National Library of Medicine. Taxonomy browser (streptomyces filamentosus). National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=67294]
[2][Chakraborty, B, et al. (2022). Streptomyces filamentosus strain KS17 isolated from microbiologically unexplored marine ecosystems exhibited a broad spectrum of anitmicrobial activity against human pathogens. Process Biochemistry, 117, 42-52. https://doi.org/10.1016/j.procbio.2022.03.010]
[3][Chater, K. (2006). Streptomyces inside-out: a new perspective on the bacteria that provide us with antibiotics. Philos Trans R Soc Lond B Biol Sci, 761–768. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1609407/]
[4][Lyu, Z.-Y., Bu, Q.-T., et al.(2022). Improving the yield and quality of daptomycin in streptomyces roseosporus by multilevel metabolic engineering. Frontiers in Microbiology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058172/]
[5][Baltz, R. H., Brian, P., Miao, V., & Wrigley, S. K. (2006). Combinatorial biosynthesis of lipopeptide antibiotics in Streptomyces roseosporus. OUP Academic. https://academic.oup.com/jimb/article/33/2/66/5992952]
[6][U.S. National Library of Medicine. Streptomyces filametosus genome assembly ASM863401v1. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_008634015.1/]
[7][Cornell, C, et al. (2018). Molecular characterization of plasmids harbored by actinomycetes isolated from the Great Salt Plains of Oklahoma using PFGE and next generation whole genome sequencing. Frontiers in Microbiology, 9. https://doi.org/10.3389/fmicb.2018.02282]
[8][BacDive. Streptomyces filamentosus: DSM 40122. https://bacdive.dsmz.de/strain/159104]
[9][Loria, R, et al. (2006). Evolution of plant pathogenicity in Streptomyces. Annual Review of Phytopathology, 44, 469-87. https://doi.org/10.1146/annurev.phyto.44.032905.091147]
[10][Wang L, Zhao Y, Liu Q, Huang Y, Hu C, Liao G. Improvement of A21978C production in Streptomyces roseosporus by reporter-guided rpsL mutation selection. Journal of Applied Microbiology. 2012;112(6):1095–1101.]e
[11][Li, L., Ma, T., Liu, Q., Huang, Y., Hu, C., & Liao, G. (2013). Improvement of daptomycin production instreptomyces roseosporus through the acquisition of Pleuromutilin Resistance. BioMed Research International, 2013, 1–6. https://doi.org/10.1155/2013/479742]
[12][ Lee, K. H., Lee, K. W., & Cha, K. H. (2019). WO2015093839A1 - new streptomyces filamentosus variant and method for producing daptomycin using same. Google Patents. https://patents.google.com/patent/WO2015093839A1/en]
[13][Lim, Y. H., Wong, F. T., Yeo, W. L., Ching, K. C., Lim, Y. W., Heng, E., Chen, S., Tsai, D., Lauderdale, T., Shia, K., Ho, Y. S., Hoon, S., Ang, E. L., Zhang, M. M., & Zhao, H. (2018). Auroramycin: A potent antibiotic from streptomyces roseosporus by crispr‐cas9 activation. ChemBioChem, 19(16), 1716–1719. https://doi.org/10.1002/cbic.201800266]
[14][Tan Y, Yao R, Wang R, Wang D, Wang G, Zheng S. Reduction of selenite to Se(0) nanoparticles by filamentous bacterium Streptomyces sp. ES2-5 isolated from a selenium mining soil. Microb Cell Fact. 2016 Sep 15;15(1):157. doi: 10.1186/s12934-016-0554-z. PMID: 27630128; PMCID: PMC5024524.]
Edited by [Julia Young], student of Jennifer Bhatnagar for BI 311 General Microbiology, 2023, Boston University.
