Carbapenem‐resistant Gram‐negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer‐membrane or are excluded by efflux mechanisms. Here, we report a cationic block β‐peptide (PAS8‐b‐PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8‐b‐PDM12 does not only compromise the integrity of the bacterial outer‐membrane, it also deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As a result, PAS8‐b‐PDM12 sensitizes carbapenem‐ and colistin‐resistant GNB to multiple antibiotics in vitro and in vivo. The β‐peptide allows the perfect alternation of cationic versus hydrophobic side chains, representing a significant improvement over previous antimicrobial α‐peptides sensitizing agents. Together, our results indicate that it is technically possible for a single adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group, including those resistant to last resort antibiotics.
Carbapenem-resistant Gram-negative bacteria (GNB) are heading the list of pathogens for whicha ntibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer-membrane or are excluded by efflux mechanisms.Here,wereport acationic block b-peptide (PAS8-b-PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8-b-PDM12 does not only compromise the integrity of the bacterial outermembrane,italso deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As ar esult, PAS8-b-PDM12 sensitizes carbapenem-and colistin-resistant GNB to multiple antibiotics in vitro and in vivo.The b-peptide allows the perfect alternation of cationic versus hydrophobic side chains,r epresenting as ignificant improvement over previous antimicrobial a-peptides sensitizing agents.T ogether, our results indicate that it is technically possible for as ingle adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group,i ncluding those resistant to last resort antibiotics. Singapore 637551 (Singapore) Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under https://doi.
We report a case of an unusually located site of acute localized exanthematous pustulosis in the right lower limb of a patient treated with beta‐lactams which resolved upon cessation. This case report highlights the need for vigilance as well as an index of suspicion for atypical presentations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.