Researchers have discovered a novel antibacterial lipopeptide produced by the bacterium Serratia marcescens that exhibits potent efficacy in killing Staphylococcus aureus, one of the most significant human pathogens.
The findings, published recently in Microbiology Spectrum, shed light on the mode of action of the lipopeptide serrawettin W2-FL10 and its potential as a therapeutic agent for treating bacterial infections in humans.
Staphylococcus aureus is among the five most common causes of hospital-acquired infections and often leads to life-threatening complications following surgery. Since the introduction of antibiotics in the early 1940s, S. aureus has developed resistance against most classes of antibiotics, including penicillin. In the past six decades, only two new classes of antibiotics with unique modes of action have been introduced onto the market, one of which is daptomycin, a lipopeptide antibiotic.
Serrawettin W2-FL10: Targeting the Cell Membrane
Dr. Tanya Decker (neé Clements) from Stellenbosch University (SU) provided the first insight into the mode of action of serrawettin W2-FL10. She demonstrated that this lipopeptide targets the cell membrane of S. aureus, causing lesions that result in the leakage of intracellular components and, ultimately, cell death.
Decker also showed that serrawettin W2-FL10 is not toxic to mammalian cells, making it a promising candidate for the treatment of bacterial infections in humans. Moreover, the structure of serrawettin W2-FL10 is much smaller than that of daptomycin (five amino acids and a C10 fatty acid chain compared to 13 amino acids and a C10 fatty acid chain), which could significantly reduce manufacturing costs.
The Origin and Collaborative Efforts Behind the Discovery
Dr. Decker began working on serrawettin W2-FL10 in 2017 in the research group of Prof. Wesaal Khan in SU’s Department of Microbiology. Her research followed the work of another postgraduate student, Dr. Thando Ndlovu, who isolated various bacterial strains from wastewater samples whose biosurfactants proved effective against antibiotic-resistant and disease-causing bacteria. In polluted environments, bacteria naturally produce biosurfactants to protect themselves against and outcompete other bacteria.
Decker’s research focused on understanding the antimicrobial activity of Serratia-derived lipopeptides, primarily in pigmented and non-pigmented S. marcescens strains. She demonstrated that these strains produced a wide range of broad-spectrum antimicrobial compounds, leading to the identification of serrawettin W2-FL10 as a promising candidate for further investigation into its antimicrobial characteristics.
Prof. Khan attributes the success of their findings thus far to close collaboration with Prof. Marina Rautenbach, a biochemist and specialist in antimicrobial peptides at SU’s Department of Biochemistry.
Decker is continuing her research into novel natural antimicrobial products at the Helmholtz Institute for Pharmaceutical Research Saarland in Germany.
