Abstract
An in-depth understanding of cell-drug binding modes and action mechanisms can potentially guide the future design of novel drugs and antimicrobial materials and help to combat antibiotic resistance. Light-harvesting π-conjugated molecules have been demonstrated for their antimicrobial effects, but their impact on bacterial outer cell envelope needs to be studied in detail. Here, we synthesized poly(phenylene) based model cationic conjugated oligo- (2QA-CCOE, 4QA-CCOE) and polyelectrolytes (CCPE), and systematically explored their interactions with the outer cell membrane of wild-type and ampicillin (amp)-resistant Gram-negative bacteria, Escherichia coli (E. coli). Incubation of the E. coli cells in CCOE/CCPE solution inhibited the subsequent bacterial growth in LB media. About 99% growth inhibition was achieved if amp-resistant E. coli was treated for ~3–5 min, 1 h and 6 h with 100 μM of CCPE, 4QA-CCOE, and 2QA-CCOE solutions, respectively. Interestingly, these CCPE and CCOEs inhibited the growth of both wild-type and amp-resistant E. coli to a similar extent. A large surface charge reversal of bacteria upon treatment with CCPE suggested the formation of a coating of CCPE on the outer surface of bacteria; while a low reversal of bacterial surface charge suggested intercalation of CCOEs within the lipid bilayer of bacteria.
Highlights
While β-lactams are widely used to treat infections associated with Gram-negative bacteria, the emergence of resistance to this class of antibiotics has led researchers to find alternative drugs
We synthesized model cationic π-conjugated oligoelectrolytes (2QA-CCOE and 4QA-CCOE) and polyelectrolyte (CCPE) with phenylene based hydrophobic backbone and propoxy pendants terminated with cationic quaternary amine groups (Fig. 1)
We explored the antimicrobial activity of conjugated 2QA-CCOE, 4QA-CCOE, and cationic conjugated polyelectrolyte (CCPE) molecules against wild-type (DH10B) and amp-resistant (SSBIO002) Gram-negative E. coli for a complex matrix of treatment conditions, including chemical structure and concentration of CCOE/CCPE in treatment systems as well as time and modes of treatments of bacterial cells
Summary
While β-lactams are widely used to treat infections associated with Gram-negative bacteria, the emergence of resistance to this class of antibiotics has led researchers to find alternative drugs. We explored the antimicrobial activity of conjugated 2QA-CCOE, 4QA-CCOE, and CCPE molecules against wild-type (DH10B) and amp-resistant (SSBIO002) (explained in the supporting information) Gram-negative E. coli for a complex matrix of treatment conditions, including chemical structure and concentration of CCOE/CCPE in treatment systems as well as time and modes of treatments of bacterial cells. The killing efficiency (UV/Vis absorbance and flow cytometry); % growth inhibition (UV/Vis absorbance and colony-forming unit (CFU) assays); surface charge reversal (zeta potential analyzer); and, morphological changes (scanning electron microscopy (SEM), and fluorescence microscopy) of treated bacteria were explored. Such rigorous effort can greatly clarify our understanding of cell-conjugated molecule binding and growth inhibition mechanism from the viewpoint of fundamental changes on the bacterial membrane. Besides aiding in drug design, this effort to unravel bacteria-organic molecule interactions can assist in the development of coating for medical devices, wound healing materials, packaging materials for food safety, prevention of marine biofouling, wastewater treatment, microbial sensing, microbial fuel cells and more
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