{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:43Z","timestamp":1792788763412,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009468","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R001111\/1"],"award-info":[{"award-number":["MR\/R001111\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/L006162\/1"],"award-info":[{"award-number":["BB\/L006162\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UKRI Strategic Priorities Fund","award":["EP\/T002778\/1"],"award-info":[{"award-number":["EP\/T002778\/1"]}]},{"name":"UKRI Strategic Priorities Fund","award":["EP\/T002778\/1"],"award-info":[{"award-number":["EP\/T002778\/1"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N002679\/1"],"award-info":[{"award-number":["MR\/N002679\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MR\/N002679\/1"],"award-info":[{"award-number":["MR\/N002679\/1"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["212197\/Z\/19\/Z"],"award-info":[{"award-number":["212197\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership","award":["MR\/N013840\/1"],"award-info":[{"award-number":["MR\/N013840\/1"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Peptidoglycan is the major structural component of the\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    cell wall, in which it maintains cellular integrity, is the interface with the host, and its synthesis is targeted by some of the most crucial antibiotics developed. Despite this importance, and the wealth of data from\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies, we do not understand the structure and dynamics of peptidoglycan during infection. In this study we have developed methods to harvest bacteria from an active infection in order to purify cell walls for biochemical analysis\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . Isolated\n                    <jats:italic>ex vivo<\/jats:italic>\n                    bacterial cells are smaller than those actively growing\n                    <jats:italic>in vitro<\/jats:italic>\n                    , with thickened cell walls and reduced peptidoglycan crosslinking, similar to that of stationary phase cells. These features suggested a role for specific peptidoglycan homeostatic mechanisms in disease. As\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    missing penicillin binding protein 4 (PBP4) has reduced peptidoglycan crosslinking\n                    <jats:italic>in vitro<\/jats:italic>\n                    its role during infection was established. Loss of PBP4 resulted in an increased recovery of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    from the livers of infected mice, which coincided with enhanced fitness within murine and human macrophages. Thicker cell walls correlate with reduced activity of peptidoglycan hydrolases.\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    has a family of 4 putative glucosaminidases, that are collectively crucial for growth. Loss of the major enzyme SagB, led to attenuation during murine infection and reduced survival in human macrophages. However, loss of the other three enzymes Atl, SagA and ScaH resulted in clustering dependent attenuation, in a zebrafish embryo, but not a murine, model of infection. A combination of\n                    <jats:italic>pbp4<\/jats:italic>\n                    and\n                    <jats:italic>sagB<\/jats:italic>\n                    deficiencies resulted in a restoration of parental virulence. Our results, demonstrate the importance of appropriate cell wall structure and dynamics during pathogenesis, providing new insight to the mechanisms of disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009468","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T13:43:51Z","timestamp":1617198231000},"page":"e1009468","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":99,"title":["Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0440-610X","authenticated-orcid":true,"given":"Joshua A. F.","family":"Sutton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8847-5489","authenticated-orcid":true,"given":"Oliver T.","family":"Carnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8105-5083","authenticated-orcid":true,"given":"Lucia","family":"Lafage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2338-0301","authenticated-orcid":true,"given":"Joe","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Biboy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-2488","authenticated-orcid":true,"given":"Josie F.","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2406-2241","authenticated-orcid":true,"given":"Eric J. G.","family":"Pollitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone C.","family":"Tazoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-4961","authenticated-orcid":true,"given":"William","family":"Turnbull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia H.","family":"Hajdamowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9157-5800","authenticated-orcid":true,"given":"Bart\u0142omiej","family":"Salamaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-3631","authenticated-orcid":true,"given":"Grace R.","family":"Pidwill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-8648","authenticated-orcid":true,"given":"Alison M.","family":"Condliffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1790-1641","authenticated-orcid":true,"given":"Stephen A.","family":"Renshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Vollmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-7805","authenticated-orcid":true,"given":"Simon 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