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

Srikkanth Balasubramanian,Usama R Abdelmohsen,Ulrike Holzgrabe,Wilma Ziebuhr,Konrad U Förstner,Richa Bharti,Joseph Skaf,Ute H Humeida,Tobias A Oelschlaeger

doi:10.3389/fmicb.2018.01473

Srikkanth Balasubramanian, Usama R Abdelmohsen + Show 7 more

Open Access

https://doi.org/10.3389/fmicb.2018.01473

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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.

Highlights

Surgical implants and medical devices have greatly assisted in improving the survival and recovery of patients from physical ailments (Vinh and Embil, 2005)
SBT348 was identified with a preliminary anti-biofilm screening of different actinomycetes organic extracts against the strong biofilm forming S. epidermidis RP62A
Scanning electron microscopy (SEM) analysis revealed the filamentous nature of Streptomyces sp

Summary

Introduction

Surgical implants and medical devices have greatly assisted in improving the survival and recovery of patients from physical ailments (Vinh and Embil, 2005). They are ideal niches for colonization and biofilm formation by microorganisms from patient’s own skin, healthcare workers’ skin, or hospitalized settings (Percival et al, 2015). Biofilms are networks of microorganisms that are entrapped in a selfproduced gluey matrix made up of polysaccharides, proteins, lipids, and eDNA (Otto, 2009; Flemming and Wingender, 2010). Current treatment of biofilm based device-related infections (DRIs) involves complete removal of the infected implant or device by a surgical procedure followed by prolonged antibiotic treatments (Otto, 2012). Lead to increased patient morbidity and mortality, and increased health care costs (Shida et al, 2013; Kleinschmidt et al, 2015; Leary et al, 2017)

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