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To expand the arsenal of treatments against antimicrobial\u2010resistant (AMR) pathogens, 600\u2010Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate \u03b2\u2010lactam antibiotics against Gram\u2010positive bacteria. BPEI binds cell\u2010wall 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\u2010positive pathogens but not Gram\u2010negative bacteria. 600\u2010Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non\u2010\u03b2\u2010lactam co\u2010drug, erythromycin, which targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL\u20108 by human epithelial keratinocytes. This enables BPEI to function as a broad\u2010spectrum antibiotic potentiator, and expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care.<\/jats:p>","DOI":"10.1002\/cmdc.202000239","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T14:10:56Z","timestamp":1591279856000},"page":"1421-1428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Expanding the Spectrum of Antibiotics Capable of Killing Multidrug\u2010Resistant <i>Staphylococcus aureus<\/i> and <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1002","volume":"15","author":[{"given":"Anh K.","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Panlilio","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Pusavat","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra L.","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika L.","family":"Moen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Biology University of Central Oklahoma  100 North University Drive Edmond OK 73034 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-405X","authenticated-orcid":false,"given":"Charles V.","family":"Rice","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  101 Stephenson Parkway Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.9b00486"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.9b00334"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00056"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.10.056"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00288"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00084"},{"key":"e_1_2_7_7_1","unstructured":"D.\u2005A. 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