{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:14:03Z","timestamp":1778854443214,"version":"3.51.4"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019721","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019721","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,5,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The antibacterial efficacy of polymyxins in lungs may be impacted by mucin. The aim of this study was to characterize\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              the effect of mucin on polymyxin B (PMB) activity against two multidrug-resistant\n              <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n              strains isolated from a patient before (AB121-D0) and after colistin treatment (AB122-D12), using a pharmacokinetic\/pharmacodynamic (PK\/PD) modeling approach. PMB binding to mucin was characterized by ultracentrifugation in cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with 1% mucin. Time-kill (TK) experiments were performed in CAMHB, with 1% mucin or without as control, and with PMB total concentrations ranging from 0.25 to 512 mg\/L based on the strain\u2019s minimum inhibitory concentration (MIC). For each strain, TK data were modeled based on unbound PMB concentrations. Bacterial resistance to PMB was investigated via MIC and whole genome sequencing from bacteria that regrew in the presence of antibiotics at the end of the TK experiments. PMB unbound fraction increased nonlinearly from 6% to 60% when total concentration increased from 0.5 to 512 mg\/L. In addition to binding to PMB, mucin had an impact on PMB activity, which differed between the two strains. For AB121-D0, PMB activity increased in the presence of mucin resulting in a reduction of the bacterial regrowth, whereas for AB122-D12, a decrease in PMB activity was observed. Mutations in genes involved in PMB resistance appeared randomly and explained only partially the bacterial regrowth observed in TK with antibiotics. This study showed that PMB binding to mucin had a real and important impact but was not the only factor explaining the impaired PMB efficacy in the presence of mucin.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01535-24","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T14:52:18Z","timestamp":1743000738000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>In vitro<\/i>\n            pharmacokinetic\/pharmacodynamic modeling of the effect of mucin on polymyxin B activity against\n            <i>Acinetobacter baumannii<\/i>"],"prefix":"10.1128","volume":"69","author":[{"given":"Mathilde","family":"Lacroix","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Poitiers INSERM, PHAR2","place":["Poitiers, France"]},{"name":"Institut Roche\u2013Boulogne-Billancourt","place":["Boulogne-Billancourt, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00e9my","family":"Moreau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Poitiers INSERM, PHAR2","place":["Poitiers, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Zampaloni","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Immunology, Infectious Disease and Ophthalmology","place":["Basel, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Bissantz","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd","place":["Basel, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Mirfendereski","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Pharmacocin\u00e9tique et Toxicologie, CHU Poitiers","place":["Poitiers, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamasseh","family":"Shirvani","sequence":"additional","affiliation":[{"name":"Institut Roche\u2013Boulogne-Billancourt","place":["Boulogne-Billancourt, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5279-6678","authenticated-orcid":true,"given":"Sandrine","family":"Marchand","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Poitiers INSERM, PHAR2","place":["Poitiers, France"]},{"name":"D\u00e9partement de Pharmacocin\u00e9tique et Toxicologie, CHU Poitiers","place":["Poitiers, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-8965","authenticated-orcid":true,"given":"William","family":"Couet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Poitiers INSERM, PHAR2","place":["Poitiers, France"]},{"name":"D\u00e9partement de Pharmacocin\u00e9tique et Toxicologie, CHU Poitiers","place":["Poitiers, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-5888","authenticated-orcid":true,"given":"Alexia","family":"Chauzy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Poitiers INSERM, PHAR2","place":["Poitiers, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-005-2598-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2019.09.012"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.5005\/jp-journals-10071-23276"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm357"},{"key":"e_1_3_3_6_2","first-page":"1254","article-title":"In vitro activity of polymyxin B against carbapenem-resistant Acinetobacter baumannii","volume":"97","author":"Thamlikitkul V","year":"2014","unstructured":"Thamlikitkul V, Tiengrim S, Seenama C. 2014. In vitro activity of polymyxin B against carbapenem-resistant Acinetobacter baumannii. J Med Assoc Thai 97:1254\u20131258.","journal-title":"J Med Assoc Thai"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2016.10.001"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24530"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.12.006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(86)90077-3"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(95)04333-0"},{"key":"e_1_3_3_12_2","unstructured":"Mucus and mucin environments reduce the efficacy of polymyxin and fluoroquinolone antibiotics against Pseudomonas aeruginosa - PMC. 2023. Available from: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9267971\/. Retrieved 15 Mar 2023."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.8b01054"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00808-15"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit334"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0359OC"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03451-23"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73469"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.09.023"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113845"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00208"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009262"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00834-10"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.770518"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02928"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190599"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88397-z"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwae085"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2024.106975"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00591-19"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00073-12"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.07.003"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.10.016"},{"key":"e_1_3_3_34_2","first-page":"1","volume-title":"Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases","author":"European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID)","year":"2003","unstructured":"European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). 2003. Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution, p 1\u20137. In Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases. Vol. 9."},{"key":"e_1_3_3_35_2","unstructured":"2024. M100Ed33 | Performance standards for antimicrobial susceptibility testing. Clinical & Laboratory Standards Institute. Available from: https:\/\/clsi.org\/standards\/products\/microbiology\/documents\/m100"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv267"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.842921"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.02.021"},{"key":"e_1_3_3_39_2","volume-title":"NCCLS","year":"1999","unstructured":"Methods for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline. 1999. In NCCLS. NCCLS document M26-A."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012299115260"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0731-7085(02)00016-x"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.733"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-016-9487-8"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12161"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01535-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01535-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T13:02:00Z","timestamp":1746622920000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01535-24"}},"subtitle":[],"editor":[{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,7]]}},"alternative-id":["10.1128\/aac.01535-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01535-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]},"assertion":[{"value":"2024-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01535-24"}}