Combating antibiotic-resistant pathogens
Researchers using the XSD 12-ID-B beamline at the APS are working towards the development of a new class of antimicrobial foldamers that may effectively combat emerging antibiotic-resistant pathogens.
The emerging antibiotic resistance poses an increasing threat to global public health. The resistance developed by multidrug-resistant pathogens including E. coli, P. aeruginosa, S. aureus, and S. epidermidis has been recognized by World Health Organization (WHO) as one of the biggest threats in the 21st century.
Thus, it is considerably significant to develop the new generation of antibiotics combating drug resistance more effectively. Natural cationic host-defense peptides (HDPs) have attracted substantial interest because they are believed to have lower risk of resistance.
Host-defense peptides (HDPs) such as magainin 2 have emerged as potential therapeutic agents combating antibiotic resistance. Inspired by their structures and mechanism of action, herein we report the first example of antimicrobial helical sulfono-γ-AApeptide foldamers. The lead molecule displays broad-spectrum and potent antimicrobial activity against multi-drug-resistant Gram-positive and Gram-negative bacterial pathogens. Time-kill studies and fluorescence microscopy suggest that sulfono-γ-AApeptides eradicate bacteria by taking a mode of action analogous to that of HDPs.
Clear structure–function relationships exist in the studied sequences. Longer sequences, presumably adopting more-defined helical structures, are more potent than shorter ones. Interestingly, the sequence with less helical propensity in solution could be more selective than the stronger helix-forming sequences. Moreover, this class of antimicrobial agents are resistant to proteolytic degradation.
Yaqiong Li, Haifan Wu, Peng Teng, Ge Bai, Xiaoyang Lin, Xiaobing Zuo, Chuanhai Cao and Jianfeng Cai, “Helical Antimicrobial Sulfono-γ-AApeptides,” Journal of Medicinal Chemisty, Article ASAP. DOI: 10.1021/acs.jmedchem.5b00537, Published May 28, 2015.