Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions. This review focuses on the effects of biological (co-cultivation), chemical, as well as molecular elicitation on secondary metabolism in actinomycetes. Our review covers the literature until June 2014 and exemplifies the diversity of natural products that have been recovered by such approaches from the phylum Actinobacteria.
Bacterial biofilms are three-dimensional networks of cells entangled in a self-generated extracellular polymeric matrix composed of proteins, lipids, polysaccharides, and nucleic acids. Biofilms can establish themselves on virtually any accessible surface and lead to varying impacts ranging from infectious diseases to degradation of toxic chemicals. Biofilms exhibit high mechanical stiffness and are inherently tolerant to adverse conditions including the presence of antibiotics, pollutants, detergents, high temperature, changes in pH, etc. These features make biofilms resilient, which is beneficial for applications in dynamic environments such as bioleaching, bioremediation, materials production, and wastewater purification. We have recently described an easy and cost-effective method for 3D printing of bacteria and have extended this technology for 3D printing of genetically engineered Escherichia coli biofilms. Our 3D printing platform exploits simple alginate chemistry for printing of a bacteria-alginate bioink mixture onto calcium-containing agar surfaces, resulting in the formation of bacteria-encapsulating hydrogels with varying geometries. Bacteria in these hydrogels remain intact, spatially patterned, and viable for several days. Printing of engineered bacteria to produce inducible biofilms leads to formation of multilayered three-dimensional structures that can tolerate harsh chemical treatments. Synthetic biology and material science approaches provide the opportunity to append a wide range of useful functionalities to these 3D-printed biofilms. In this article, we describe the wide range of future applications possible for applying functional 3D-printed biofilms to the construction of living biofilm-derived materials in a large-scale and environmentally stable manner.
Living materials, which are fabricated by encapsulating living biological cells within a non‐living matrix, have gained increasing attention in recent years. Their fabrication in spatially defined patterns that are mechanically robust is essential for their optimal functional performance but is difficult to achieve. Here, a bioprinting technique employing environmentally friendly chemistry to encapsulate microalgae within an alginate hydrogel matrix is reported. The bioprinted photosynthetic structures adopt pre‐designed geometries at millimeter‐scale resolution. A bacterial cellulose substrate confers exceptional advantages to this living material, including strength, toughness, flexibility, robustness, and retention of physical integrity against extreme physical distortions. The bioprinted materials possess sufficient mechanical strength to be self‐standing, and can be detached and reattached onto different surfaces. Bioprinted materials can survive stably for a period of at least 3 days without nutrients, and their life can be further extended by transferring them to a fresh source of nutrients within this timeframe. These bioprints are regenerative, that is, they can be reused and expanded to print additional living materials. The fabrication of the bioprinted living materials can be readily up‐scaled (up to ≥70 cm × 20 cm), highlighting their potential product applications including artificial leaves, photosynthetic bio‐garments, and adhesive labels.
Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections.
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