{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Russo TA"],"funding":["BLRD VA","U.S. Department of Veterans Affairs"],"pagination":["e0103322"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9872597"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(1)"],"pubmed_abstract":["Limited therapeutic options dictate the need for new classes of antimicrobials active against carbapenem-resistant Acinetobacter baumannii. Presented data confirm and extend penicillin binding protein 7/8 (PBP 7/8) as a high-value target in the CR A. baumannii strain HUMC1. PBP 7/8 was essential for optimal growth/survival of HUMC1 in <i>ex vivo</i> human ascites and in a rat subcutaneous abscess model; in a mouse pneumonia model, the absence of PBP 7/8 decreased lethality 11-fold. The loss of PBP 7/8 resulted in increased permeability, sensitivity to complement, and lysozyme-mediated bactericidal activity. These changes did not appear to be due to alterations in the cellular fatty acid composition or capsule production. However, a decrease in lipid A and an increase in coccoidal cells and cell aggregation were noted. The compromise of the stringent permeability barrier in the PBP 7/8 mutant was reflected by an increased susceptibility to several antimicrobials. Importantly, expression of <i>ampC</i> was not significantly affected by the loss of PBP 7/8 and serial passage of the mutant strain in human ascites over 7 days did not yield revertants possessing a wild-type phenotype. In summary, these data and other features support PBP 7/8 as a high-value drug target for extensively drug-resistant and CR A. baumannii. Our results guide next-stage studies; the determination that the inactivation of PBP 7/8 results in an increased sensitivity to lysozyme enables the design of a high-throughput screening assay to identify small molecule compounds that can specifically inhibit PBP 7/8 activity."],"journal":["Antimicrobial agents and chemotherapy"],"pubmed_title":["Penicillin Binding Protein 7/8 Is a Potential Drug Target in Carbapenem-Resistant Acinetobacter baumannii."],"pmcid":["PMC9872597"],"funding_grant_id":["I01 BX004677","1I01BX004677-01A1","I01 BX000984","1I01BX000984"],"pubmed_authors":["Alvarado CL","Zang M","Trivedi G","Hutson A","Davies CJ","Carlino-MacDonald U","Barnes O","Adams FG","Mathur P","Ascari A","Eijkelkamp BA","Russo TA"],"additional_accession":[]},"is_claimable":false,"name":"Penicillin Binding Protein 7/8 Is a Potential Drug Target in Carbapenem-Resistant Acinetobacter baumannii.","description":"Limited therapeutic options dictate the need for new classes of antimicrobials active against carbapenem-resistant Acinetobacter baumannii. Presented data confirm and extend penicillin binding protein 7/8 (PBP 7/8) as a high-value target in the CR A. baumannii strain HUMC1. PBP 7/8 was essential for optimal growth/survival of HUMC1 in <i>ex vivo</i> human ascites and in a rat subcutaneous abscess model; in a mouse pneumonia model, the absence of PBP 7/8 decreased lethality 11-fold. The loss of PBP 7/8 resulted in increased permeability, sensitivity to complement, and lysozyme-mediated bactericidal activity. These changes did not appear to be due to alterations in the cellular fatty acid composition or capsule production. However, a decrease in lipid A and an increase in coccoidal cells and cell aggregation were noted. The compromise of the stringent permeability barrier in the PBP 7/8 mutant was reflected by an increased susceptibility to several antimicrobials. Importantly, expression of <i>ampC</i> was not significantly affected by the loss of PBP 7/8 and serial passage of the mutant strain in human ascites over 7 days did not yield revertants possessing a wild-type phenotype. In summary, these data and other features support PBP 7/8 as a high-value drug target for extensively drug-resistant and CR A. baumannii. Our results guide next-stage studies; the determination that the inactivation of PBP 7/8 results in an increased sensitivity to lysozyme enables the design of a high-throughput screening assay to identify small molecule compounds that can specifically inhibit PBP 7/8 activity.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-06-13T06:14:32.087Z","creation":"2025-04-05T21:08:19.326Z"},"accession":"S-EPMC9872597","cross_references":{"pubmed":["36475717"],"doi":["10.1128/aac.01033-22"]}}