Uptake of monoaromatic hydrocarbons during biodegradation by FadL channel-mediated lateral diffusion

Journal article

The topic of this research was initiated by the discovery, in part by Dr. David Giles, that Vibrio cholerae, the enteric bacteria responsible for the disease cholera, has the ability to uptake and utilize long chain polyunsaturated fatty acids up to 22 carbon atoms long. Before this discovery was made, conventional belief was that fatty acids of greater than 18 carbons long were toxic to bacteria. Further investigations have revealed that this uptake is not unique to Vibrio cholerae, and a range of bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and even Escherichia coli have been found to uptake and use these longer chain fatty acids to varying degrees. This uptake has been linked to increased antimicrobial resistance, motility, biofilm formation, and virulence phenotypes. This research was a collaboration between Dr. David Giles and Dr. Bradley Harris to computationally investigate the uptake mechanism for the uptake of long chain fatty acids, as well as the effects these long-chain fatty acid integrated phospholipids have on antimicrobial resistance. The investigation was performed in two parts; the first involving the uptake of fatty acids by the long chain fatty acid transport protein FadL; the second a membrane system interacting with cationic antimicrobial peptides. The FadL uptake study involved the atomistic level modelling of various FadL homologs found in virulent V. cholerae serotypes. Docking of equilibrated FadL homologs presented information on the binding energies and binding locations of each fatty acid tested for a wide range of conformations. The summation of the binding locations revealed preferred binding sites and oftentimes the channels between them. To investigate cationic resistance, atomistic membrane systems were generated with varying fatty acids replacing the phospholipid tail groups. For each of the test membranes, various cationic antimicrobial peptides were pulled through the membrane systems using steered molecular dynamics. The membrane permeability for each fatty acid was analyzed from the energy required to move the cationic peptide through the membrane as well as the response of the membrane structure as the peptide passed through. Future suggested studies would include steered molecular dynamics for fatty acid transport through each FadL homolog. This would verify the found channels and investigate any conformational shifts in structure to accommodate the passage of the fatty acid. For the membrane permeability study, additional peptides could be tested as well as systems using the outer membrane of gram-negative bacteria. Additional studies using less complex membrane leaflets may also be insightful

Authors: Somboon, K; Doble, A; Bulmer, D; Baslé, A; Khalid, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 11
• Issue: 1
• Pages: 6331-6331
• Publication date: 2020-12-10
• DOI: 10.1038/s41467-020-20126-y
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Lipopolysaccharide; Escherichia coli; Biochemistry; Bacterial outer membrane; Bacteria; Chemical engineering; Biology; Biophysics; Biodegradation; Facilitated diffusion; Membrane; Diffusion; Quorum sensing; Chemistry; Periplasmic space; Organic chemistry; Biofilm; Pollutant