Journal
SCIENCE ADVANCES
Volume 6, Issue 27, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb9593
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Funding
- National Natural Science Foundation of China [21925405, 201874005, 21635002]
- Shaanxi Provincial Science Fund for Distinguished Young Scholars [2018JC-011]
- National Key Research and Development Program of China [2018YFA0208800]
- Chinese Academy of Sciences [XDA23030106, YJKYYQ20180044]
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beta-Lactam-resistant (BLR) Gram-negative bacteria that are difficult or impossible to treat are causing a global health threat. However, the development of effective nanoantibiotics is limited by the poor understanding of changes in the physical nature of BLR Gram-negative bacteria. Here, we systematically explored the nanomechanical properties of a range of Gram-negative bacteria (Salmonella, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae) with different degrees of beta-lactam resistance. Our observations indicated that the BLR bacteria had cell stiffness values almost 10x lower than that of beta-lactam-susceptible bacteria, caused by reduced peptidoglycan biosynthesis. With the aid of numerical modeling and experimental measurements, we demonstrated that these stiffness findings can be used to develop programmable, stiffness-mediated antimicrobial nanowires that mechanically penetrate the BLR bacterial cell envelope. We anticipate that these stiffness-related findings will aid in the discovery and development of novel treatment strategies for BLR Gram-negative bacterial infections.
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