{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:56:27Z","timestamp":1784912187997,"version":"3.55.0"},"reference-count":77,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CRG\/2021\/003598"],"award-info":[{"award-number":["CRG\/2021\/003598"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["IF180902"],"award-info":[{"award-number":["IF180902"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001862","name":"The Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"crossref"}]},{"name":"KAW Foundation"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,4,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Peptidoglycan (PG)-modifying enzymes play a crucial role in cell wall remodeling, essential for growth and division. Cell wall degradation products are transported to the cytoplasm and recycled back in most gram-negative bacteria, and PG recycling is also linked to \u03b2-lactam resistance in many bacteria.\n              <jats:italic>Caulobacter crescentus<\/jats:italic>\n              is intrinsically resistant to \u03b2-lactams. Recently, it was shown that a soluble lytic transglycosylase, SdpA, is essential for \u03b2-lactam resistance. However, the precise role of SdpA in \u03b2-lactam resistance is unknown. This study investigated the PG recycling pathway and its role in antibiotic resistance in\n              <jats:italic>C. crescentus<\/jats:italic>\n              . Anhydromuropeptides generated by the action of lytic transglycosylases (LTs) are transported to the cytoplasm by the permease AmpG.\n              <jats:italic>C. crescentus<\/jats:italic>\n              encodes an\n              <jats:italic>ampG<\/jats:italic>\n              homolog, and deletion mutants of\n              <jats:italic>sdpA<\/jats:italic>\n              and\n              <jats:italic>ampG<\/jats:italic>\n              are sensitive to \u03b2-lactams. The\n              <jats:italic>ampG<\/jats:italic>\n              deletion mutant displays a significant accumulation of anhydromuropeptides in the periplasm of\n              <jats:italic>C. crescentus,<\/jats:italic>\n              demonstrating its essential role in PG recycling. While single knockout mutants of\n              <jats:italic>sdpA<\/jats:italic>\n              and\n              <jats:italic>ampG<\/jats:italic>\n              exhibit no growth defects, double-deletion mutants (\u2206\n              <jats:italic>sdpA<\/jats:italic>\n              \u2206\n              <jats:italic>ampG<\/jats:italic>\n              ) exhibit severe growth and morphological defects. These double mutants also show enhanced sensitivity to \u03b2-lactams. Analysis of soluble muropeptides in wild-type (WT), \u2206\n              <jats:italic>sdpA<\/jats:italic>\n              , and \u2206\n              <jats:italic>ampG<\/jats:italic>\n              mutants revealed reduced levels of PG precursors (UDP-GlcNAc, UDP-MurNAc, and UDP-MurNAc-P5), suggesting that PG recycling products contribute toward\n              <jats:italic>de novo<\/jats:italic>\n              PG biosynthesis. Furthermore, supplementing the growth media with GlcNAc sugar enhanced the fitness of \u2206\n              <jats:italic>sdpA<\/jats:italic>\n              and \u2206\n              <jats:italic>ampG<\/jats:italic>\n              mutants under \u03b2-lactam stress. In conclusion, our study indicates that defects in PG recycling compromise cell wall biogenesis, leading to antibiotic sensitivity in\n              <jats:italic>C. crescentus<\/jats:italic>\n              .\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>\n                <jats:bold>IMPORTANCE<\/jats:bold>\n              <\/jats:title>\n              <jats:p>\n                \u03b2-lactam antibiotics target the peptidoglycan cell wall biosynthetic pathway in bacteria. In response to antibiotic pressures, bacteria have developed various resistance mechanisms. In many gram-negative species, cell wall degradation products are transported into the cytoplasm and induce the expression of \u03b2-lactamase enzymes. In this study, we investigated the cell wall recycling pathway and its role in antibiotic resistance in\n                <jats:italic>Caulobacter crescentus<\/jats:italic>\n                . Based on our data and prior studies, we propose that cell wall degradation products are utilized for the synthesis of peptidoglycan precursors in the cytoplasm. A deficiency in cell wall recycling leads to cell wall defects and increased antibiotic sensitivity in\n                <jats:italic>C. crescentus<\/jats:italic>\n                . These findings are crucial for understanding antibiotic resistance mechanisms in bacteria.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02975-24","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T13:02:27Z","timestamp":1741698147000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Deficiency in peptidoglycan recycling promotes \u03b2-lactam sensitivity in\n            <i>Caulobacter crescentus<\/i>"],"prefix":"10.1128","volume":"16","author":[{"given":"Malvika","family":"Modi","sequence":"first","affiliation":[{"name":"Department of Life Sciences, School of Natural Sciences, Shiv Nadar Institution of Eminence","place":["Gautam Buddha Nagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Natural Sciences, Shiv Nadar Institution of Eminence","place":["Gautam Buddha Nagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6848-5134","authenticated-orcid":true,"given":"Michael C.","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Ume\u00e5 Centre for Microbial Research, Ume\u00e5 University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-718X","authenticated-orcid":true,"given":"Felipe","family":"Cava","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Ume\u00e5 Centre for Microbial Research, Ume\u00e5 University","place":["Ume\u00e5, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8613-9438","authenticated-orcid":true,"given":"Richa","family":"Priyadarshini","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Natural Sciences, Shiv Nadar Institution of Eminence","place":["Gautam Buddha Nagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2009.12.004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","unstructured":"Typas A Banzhaf M Gross CA Vollmer W. 2012. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Available from: https:\/\/doi.org\/10.1038\/nrmicro2677","DOI":"10.1038\/nrmicro2677"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00094.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","unstructured":"den Blaauwen T de Pedro MA Nguyen-Dist\u00e8 Che MA Ayala JA. 2008. Morphogenesis of rod-shaped sacculi. Available from: https:\/\/doi.org\/10.1111\/j.1574-6976.2007.00090.x","DOI":"10.1111\/j.1574-6976.2007.00090.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00030-07"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0923-2508(90)90017-k"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02529958"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00099.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00022-11"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00428-22"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0031"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.163.1.305-310.1985"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.52.4.554-567.1988"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06792.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2024.11.004"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.23.6434-6436.2002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.15.4108"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02268.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.17.4836-4840.2000"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.11.3643-3649.2005"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.18.5347-5352.1996"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00923-16"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02725"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01256-09"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04200.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002571"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10586-2"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2014.05.011"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.00333-22"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2008\/022772-0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81928-5"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.128"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.150.2.528-534.1982"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1986.tb04704.x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.2.428-432.2000"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2017.1337705"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00013"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01292"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.23.7192-7198.1999"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73178"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13775"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3013"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340220305"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.286"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/br.28.3.231-295.1964"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06706.x"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fny065"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-021-00446-7"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00009-10"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01731.x"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35607-5"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911674106"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06432.x"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(01)03152-0"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00331"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9025566"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.2.224"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.3.583-589.2000"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.15.4233-4239.2002"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2014.0036"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1974.tb43277.x"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00448-09"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1289"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00102-17"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00092-17"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107578"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057579"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00306-15"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05720.x"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm818"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-017-0781-9"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1183-784"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.132.1.294-301.1977"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13264"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.22.10881"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-8-91"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006999"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02975-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02975-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T13:05:51Z","timestamp":1744203951000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.02975-24"}},"subtitle":[],"editor":[{"given":"Nina R.","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Joseph P.","family":"Dillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":77,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,9]]}},"alternative-id":["10.1128\/mbio.02975-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02975-24","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]},"assertion":[{"value":"2024-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02975-24"}}