Elicitation of Cryptic Secondary Metabolites and Antibacterial Activities from Mangrove and Cave Soil Actinomycetes

Actinomycetes’ secondary metabolites have received considerable attention due to their many beneficial biological activities. However, many biosynthetic gene clusters in actinomycetes remain silent as they are not transcribed under standard laboratory conditions. Therefore, this study aims to introduce antibiotic elicitors to activate cryptic secondary metabolites in soil actinomycetes and screen them for antibacterial potential. A total of 20 cave and 10 mangrove soil actinomycete isolates were exposed to streptomycin or erythromycin at subinhibitory concentration (0.5–1048 μg/mL) in minimal media. The ethyl acetate extracts were subjected to high-performance liquid chromatography (HPLC) profiling to observe the effect of elicitors towards secondary metabolite production. As a result, 61.7% of the isolates showed a positive impact (appearance of ‘new’/increase in metabolite production) when elicitors were supplemented. These changes were more pronounced in erythromycin-induced media (63.3%) than in streptomycin (60.0%). Two isolates (CS3PT50 and CS3PT53) exhibited significant changes in the profile, with additional peaks detected at 210 and 245 nm, which may indicate the production of new metabolites. More antibacterial activities were observed from stimulated (26.7%) as opposed to non-stimulated isolates (10.0%), including 6 new activities, 1 improved, and 1 decrease in inhibitory. Furthermore, isolate CS3PT53 (0.5 mg/disc) displayed broad-spectrum activities, inhibiting S. aureus ATCC 25923 and S. Typhimurium ATCC 14028. The hit actinomycete isolates belonged to the genus Streptomyces (55.6%), Norcardia (22.2%), Norcardiopsis, and Saccharomonospora (11.1%). Overall, this study demonstrated that incorporating antibiotic elicitor at subinhibitory concentration could effectively trigger the production of cryptic secondary metabolites with antibacterial properties in soil actinomycetes.