A New Bioactive Compound From the Marine Sponge-Derived Streptomyces sp. SBT348 Inhibits Staphylococcal Growth and Biofilm Formation

Abstract

Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 μg/ml) and biofilm formation (sub-MIC range: 1.95–<31.25 μg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs.

Galleria mellonella as a consolidated in vivo model hosts: New developments in antibacterial strategies and novel drug testing

“…Discrepancies in antimicrobial activity between in vitro and in vivo experiments are often observed. For example, associations of already known drugs [4], probiotic function in humans [110], and even novel synthetic molecules with good in vitro activity can have the same or a reduced level of effectiveness or they may not be effective at all when tested with G. mellonella in vivo models [83,84,86,90,92]. This may be because common in vitro models for susceptibility testing (MIC determination methods and checkerboard assay) involve contact between the bacterium and the drug in a suitable medium, lacking numerous factors present in the in vivo models such as the cellular and humoral immunity of the host.…”

“…The antibacterial action observed in vitro against S. epidermidis RP62A was not confirmed in the in vivo model G. mellonella. Indeed SKC3 had not protected the larvae from an infection of S. aureus USA300 Lac (community-acquired MRSA isolated from a wrist cancer) [92].…”

Streptomyces tirandamycinicus sp. nov., a Novel Marine Sponge-Derived Actinobacterium With Antibacterial Potential Against Streptococcus agalactiae

“…Marine actinomycetes, particularly marine sponge-associated actinomycetes have gained considerable attention during the last decade as a vast source of novel natural products (NPs) with variety of bioactivities, including anti-biofilm ( Balasubramanian et al, 2017 , 2018 ), anti-chlamydial ( Reimer et al, 2015 ; Cheng et al, 2016 ), antimicrobial ( El-Gendy and El-Bondkly, 2010 ; Elsayed et al, 2018 ), antioxidant ( Grkovic et al, 2014 ; Cheng et al, 2016 ), antiparasitic ( Elsayed et al, 2017 ), antitumor ( Yi-Lei et al, 2014 ; Yan et al, 2017 ), and immunomodulatory ( Tabares et al, 2011 ) activities. These diverse bioactive NPs are represented by alkaloids ( Elsayed et al, 2017 ), polyketides ( Schneemann et al, 2010 ), peptides ( Cheng et al, 2017 ), quinolone ( Cheng et al, 2016 ), and anthraquinones ( Abdelfattah et al, 2018 ).…”

Streptomyces from traditional medicine: sources of new innovations in antibiotic discovery

“…Other researchers have isolated new compounds from Streptomyces associated with marine sponges in the Vietnam Sea, some of which are completely novel compounds active against both Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis [46]. Under certain conditions, these new bioactive compounds can also inhibit bacterial biofilm formation [47].…”