Antimicrobial elements discovered as possible leads to new antibiotics
The rise of antibiotic resistance in microorganisms is a concerning situation and leads to the necessity to develop novel antimicrobial medicines. Microbiologist Soraya Omardien, together with her colleagues from UvA’s Swammerdam Institute of Life Sciences (SILS) performed four years of research on novel ways to fight dangerous bacteria. The results of her research show promising antimicrobial proteins that occur naturally in the immune system of humans.
The team improved a screening method using software “SporeTrackerX” to detect novel antibiotic compounds. They analysed live imaging data from experiments on model organisms Bacillus subtilis and the food-borne pathogen Bacillus cereus. Both are representatives of bacterial spore forming organisms. This makes them difficult to eradicate because spores are highly stress resistant. By performing live imaging, effects on individual bacteria and their spores can be followed in close detail, for example effects on germination and outgrowth. This is important for the identification of promising new lead antimicrobials that may form the basis of effective antibiotics of the future.
Understanding the mode-of-action of human antimicrobial peptides
The research group, together with Dr. Bas Zaat from the AMC, also studied three peptides with antimicrobial effects that are derivatives of antimicrobial proteins naturally occurring in the human body. Since the mode of action of antimicrobial peptides is substantially different from existing antibiotics, knowledge of this can be highly important in the battle against antibiotic resistance.
The peptides studied are based on proteins found in the human immune system. By combining imaging techniques with a transcriptomic approach, they were able to elucidate the mode of action of these peptides against spore forming bacteria. The peptides attack the bacteria in different ways, making it difficult for the bacteria to develop resistance. They perturb the membrane and cause a stress response in the bacterial cell envelope. In a large proportion tested bacteria, presence of the peptides leads to the formation of vast domains of increased fluidity in the plasma membrane that surrounds the cells. This ultimately promotes cell death, making them very promising candidates as future antimicrobial agents of practical use.
The research team
The work was done at the research group Molecular Biology and Microbial Food Safety, chaired by prof. Stanley Brul, in close collaboration with the Bacterial Cell Biology group of prof. Leendert Hamoen and Dr. Bas Zaat of the Medical Microbiology department at the AMC. Soraya Omardien performed the work as part of her PhD thesis “Mechanistic study of novel antimicrobials for infection prevention and cure” that she successfully defended on the 20th of April 2018 with prof. Brul (SILS) as promotor and Dr. Zaat (AMC) as copromotor.
Soraya Omardien, Jan W. Drijfhout, Henk van Veen, Soraya Schachtschabel, Martijn Riool, Leendert W. Hamoen, Stanley Brul and Sebastian A.J. Zaat, Synthetic antimicrobial peptides delocalize membrane bound proteins thereby inducing a cell envelope stress response, Biochimica et Biophysica Acta (BBA) – Biomembranes, published online 9 June 2018. Doi: 10.1016/j.bbamem.2018.06.005
Soraya Omardien, Jan W. Drijfhour, Frédéric M. Vaz, Michaela Wenzel, Leendert W. Hamoen, Sebastiaan A.J. Zaat and Stanley Brul. Bactericidal activity of amphipathic cationic antimicrobial peptides involves altering the membrane fluidity when interacting with the phospholipid bilayer, Biochimica et Biophysica Acta (BBA)- Biomembranes, published online 11 June 2018. Doi:10.1016/j.bbamem.2018.06.004
Soraya Omardien, Alexander Ter Beek, Norbert Vischer, Roy Montijn, Frank Schuren and Stanley Brul, Evaluating novel synthetic compounds active against Bacillus subtilis and Bacillus cereus spores using Live imaging with SporeTrackerX, Scientific Reports, published online 14 June 2018. Doi: 10.1038/s41598-018-27529-4