In view of the fast depleting armamentarium of drugs against significant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA) and others due to rapidly emerging drug-resistance, the discovery and development of new drugs need urgent action. In this endeavor, a new strain of endophytic actinobacterium was isolated from the plant Datura metel, which produced secondary metabolites with potent anti-infective activities. The isolate was identified as Streptomyces californicus strain ADR1 based on 16S rRNA gene sequence analysis. Metabolites produced by the isolate had been investigated for their antibacterial attributes against important pathogens: S. aureus, MRSA, S. epidermis, Enterococcus faecium and E. faecalis. Minimum inhibitory concentration (MIC₉₀) values against these pathogens varied from 0.23 ± 0.01 to 5.68 ± 0.20 μg/mL. The metabolites inhibited biofilm formation by the strains of S. aureus and MRSA (Biofilm inhibitory concentration [BIC₉₀] values: 0.74 ± 0.08–4.92 ± 0.49 μg/mL). The BIC₉₀ values increased in the case of pre-formed biofilms. Additionally, the metabolites possessed good antioxidant properties, with an inhibitory concentration (IC₉₀) value of 217.24 ± 6.77 µg/mL for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging. An insight into different classes of compounds produced by the strain ADR1 was obtained by chemical profiling and GC-MS analysis, wherein several therapeutic classes, for example, alkaloids, phenolics, terpenes, terpenoids and glycosides, were discovered.

Streptomyces spp. are known producers of therapeutically important secondary metabolites with diversity in structure and function. Optimization of different bioprocess parameters towards the improved productivity and activity profile is always considered to be of high significance. Peptone is an acclaimed source of nutrients that had been studied for its effect on the bioactivity of metabolites produced during media development. In the present communication, we report remarkable variation in the profile and anti-Candida activity of the metabolites produced by Streptomyces chrestomyceticus strain ADP4 in response to variation in the source of peptone. It was found that peptone procured from different manufactures (Himedia, CDH and Diffco) have shown noteworthy variation when used as a component of Sabouraud Dextrose Broth (SDB). The zone of inhibition, values of minimum inhibitory concentration (MIC₉₀) against C. krusei and the yield of metabolites varied significantly when the metabolites were produced in SDB medium using peptones from above mentioned sources. CDH-peptone was found to be the best for anti-Candida activity with highest zone of inhibition of 38 ± 2.0 mm and MIC₉₀ value of 2.877 ± 0.22 µg/mL against C. krusei ATCC 6258. Activity against C. albicans ATCC 10231, C. tropicalis ATCC 750, C. parapsilosis ATCC 90028 and C. auris CBS 12372 was also better as compared to the activities obtained using other peptones. The total yield of the metabolites was approximately twice in SDB with CDH-peptone as compared to those with peptone from HiMedia and Diffco. Analyses of the metabolites by using TLC and HPLC demonstrated a clear and significant difference in their profile. Since peptone is a major nitrogen source, it may be inferred that nitrogen source may play a critical role in regulation of biosynthetic gene clusters associated with synthesis of anti-Candida compounds by S. chrestomyceticus ADP4.

Staphylococcus aureus is a gram positive, tissue colonizer pathogen in humans. It is known for its tendency to build up biofilm which is a major cause of antibiotic resistance. To overcome this problem, there is an urgent requirement to discover novel antimicrobial compounds against new bacterial targets and drug resistance. In this direction the actinobacteria inhabiting special niche like plant tissues can be promising agents for novel compounds against methicillin sensitive and resistant S. aureus (MRSA). The ethyl acetate extract of Streptomyces sp. ADR1 is found to be a strong inhibitor of various Staphylococcus sp. and its resistant strain MRSA with very low MIC₉₀ values; <31.25 µg/ml. The extract was found to inhibit biofilm formation as well as preformed biofilms of S. aureus and MRSA to a significant extent.