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Expanding the Spectrum of Antibiotics Capable of Killing Multidrug‐Resistant Staphylococcus aureus and Pseudomonas aeruginosa
Author(s) -
Lam Anh K.,
Panlilio Hannah,
Pusavat Jennifer,
Wouters Cassandra L.,
Moen Erika L.,
Brennan Robert E.,
Rice Charles V.
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000239
Subject(s) - microbiology and biotechnology , pseudomonas aeruginosa , antibiotics , staphylococcus aureus , antibiotic resistance , teichoic acid , antimicrobial , bacteria , biology , penicillin , pathogenic bacteria , genetics
Infections from antibiotic‐resistant Staphylococcus aureus and Pseudomonas aeruginosa are a serious threat because reduced antibiotic efficacy complicates treatment decisions and prolongs the disease state in many patients. To expand the arsenal of treatments against antimicrobial‐resistant (AMR) pathogens, 600‐Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate β‐lactam antibiotics against Gram‐positive bacteria. BPEI binds cell‐wall teichoic acids and disables resistance factors from penicillin binding proteins PBP2a and PBP4. This study describes a new mechanism of action for BPEI potentiation of antibiotics generally regarded as agents effective against Gram‐positive pathogens but not Gram‐negative bacteria. 600‐Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non‐β‐lactam co‐drug, erythromycin, which targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL‐8 by human epithelial keratinocytes. This enables BPEI to function as a broad‐spectrum antibiotic potentiator, and expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care.