{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:13:55Z","timestamp":1788225235926,"version":"build-2803163510"},"reference-count":15,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"DHAC | National Health and Medical Research Council","award":["APP1059354, APP631632, APP1026922, APP1113719, AF51105"],"award-info":[{"award-number":["APP1059354, APP631632, APP1026922, APP1113719, AF51105"]}]},{"name":"DHAC | National Health and Medical Research Council","award":["APP1113719"],"award-info":[{"award-number":["APP1113719"]}]},{"name":"DHAC | National Health and Medical Research Council","award":["APP1113719"],"award-info":[{"award-number":["APP1113719"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["094977\/Z\/10\/Z"],"award-info":[{"award-number":["094977\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bacteremic\n                    <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                    pneumonia is one of the most severe forms of invasive pneumococcal disease (IPD) and with particularly high case-fatality rates among the elderly and individuals with comorbidities, exacerbated by rising antibiotic resistance and time to initiation of therapy. Here, we examined the efficacy of the preclinical \u201cvancapticin\u201d glycopeptide MCC5145 against fulminant infection by\n                    <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                    serotype 2 strain D39 in a bioluminescent, neutropenic mouse model of bacteremic pneumonia. MCC5145 is a semisynthetic vancomycin derivative chemically modified at the\n                    <jats:italic toggle=\"yes\">C<\/jats:italic>\n                    -terminus with a membrane-targeting motif designed to preferentially bind the anionic bacterial surface. We show that similar to vancomycin, subcutaneous administration of MCC5145 to mice 1 day after intranasal infection with a bioluminescent derivative of\n                    <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                    D39 elicited time and concentration-dependent reduction in total flux in the lungs and blood. Together, our finding supports the further development of MCC5145 as a potential new treatment option for pneumonia and\/or bacteremic pneumonia in clinical settings, particularly for immunocompromised individuals.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      (the pneumococcus) causes severe community acquired lung and blood infection, especially among the elderly and people with underlying medical conditions and\/or weakened immune systems. The rising incidence of antibiotic resistance and delays between diagnosis of infection and commencement of effective therapy make treatment difficult and result in high mortality rates. In this work, we show that a new derivative (MCC5145) of an existing antibiotic (vancomycin) rapidly eradicated lethal pneumococcal challenge from the lungs and blood of mice with a suppressed immune system. Our findings support that MCC5145 is a promising option for the treatment of lung and blood infections caused by the pneumococcus at point-of-care settings, particularly for the elderly and individuals with a weakened immune system.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.04459-22","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:00:41Z","timestamp":1692694841000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Impact of the new membrane-targeting lipoglycopeptide antibiotic MCC5145 on the treatment of bacteremic pneumococcal pneumonia in mice"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-5629","authenticated-orcid":false,"given":"Abiodun D.","family":"Ogunniyi","sequence":"first","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide","place":["Roseworthy, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide","place":["Roseworthy, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl A.","family":"Hansford","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-5770","authenticated-orcid":false,"given":"Darren J.","family":"Trott","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide","place":["Roseworthy, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A. T.","family":"Blaskovich","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30310-4"},{"key":"e_1_3_2_3_2","first-page":"12463","article-title":"Severe pneumonia in the elderly: a multivariate analysis of risk factors","volume":"8","author":"Li W","year":"2015","unstructured":"Li W , Ding C , Yin S . 2015. Severe pneumonia in the elderly: a multivariate analysis of risk factors. Int J Clin Exp Med 8:12463\u201312475.","journal-title":"Int J Clin Exp Med"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12461"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e3283385653"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ368"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.8289"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa157"},{"key":"e_1_3_2_9_2","unstructured":"Musher DM Daniel J Bond S . 2017. Resistance of Streptococcus pneumoniae to beta-lactam antibiotics. Waltham MA UpToDate. https:\/\/www.medilib.ir\/uptodate\/show\/7034."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/430352"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj2381"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00943-09"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00310-10"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-6-55"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00295-12"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01161-07"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04459-22","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04459-22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:25:11Z","timestamp":1788222311000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.04459-22"}},"subtitle":[],"editor":[{"given":"Tomefa E.","family":"Asempa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,17]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10,17]]}},"alternative-id":["10.1128\/spectrum.04459-22"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.04459-22","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,17]]},"assertion":[{"value":"2022-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04459-22"}}