{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:46:19Z","timestamp":1791294379365,"version":"4.1.0"},"reference-count":92,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,4]],"date-time":"2012-01-04T00:00:00Z","timestamp":1325635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The<jats:italic>Bacillus subtilis<\/jats:italic>extracytoplasmic function (ECF) \u03c3 factor \u03c3<jats:sup>M<\/jats:sup>is inducible by, and confers resistance to, several cell envelope\u2010acting antibiotics. Here, we demonstrate that \u03c3<jats:sup>M<\/jats:sup>is responsible for intrinsic \u03b2\u2010lactam resistance, with \u03c3<jats:sup>X<\/jats:sup>playing a secondary role. Activation of \u03c3<jats:sup>M<\/jats:sup>upregulates several cell wall biosynthetic enzymes including one, PBP1, shown here to be a target for the beta\u2010lactam cefuroxime. However, \u03c3<jats:sup>M<\/jats:sup>still plays a major role in cefuroxime resistance even in cells lacking PBP1. To better define the role of \u03c3<jats:sup>M<\/jats:sup>in \u03b2\u2010lactam resistance, we characterized suppressor mutations that restore cefuroxime resistance to a<jats:italic>sigM<\/jats:italic>null mutant. The most frequent suppressors inactivated<jats:italic>gdpP<\/jats:italic>(<jats:italic>yybT<\/jats:italic>) which encodes a cyclic\u2010di\u2010AMP phosphodiesterase (PDE). Intriguingly, \u03c3<jats:sup>M<\/jats:sup>is a known activator of<jats:italic>disA<\/jats:italic>encoding one of three paralogous diadenylate cyclases (DAC). Overproduction of the GdpP PDE greatly sensitized cells to \u03b2\u2010lactam antibiotics. Conversely, genetic studies indicate that at least one DAC is required for growth with depletion leading to cell lysis. These findings support a model in which c\u2010di\u2010AMP is an essential signal molecule required for cell wall homeostasis. Other suppressors highlight the roles of ECF \u03c3 factors in counteracting the deleterious effects of autolysins and reactive oxygen species in \u03b2\u2010lactam\u2010treated cells.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2011.07953.x","type":"journal-article","created":{"date-parts":[[2011,12,28]],"date-time":"2011-12-28T21:59:47Z","timestamp":1325109587000},"page":"623-639","source":"Crossref","is-referenced-by-count":249,"title":["Analysis of the role of<i>Bacillus subtilis<\/i>\u03c3<sup>M<\/sup>in \u03b2\u2010lactam resistance reveals an essential role for c\u2010di\u2010AMP in peptidoglycan homeostasis"],"prefix":"10.1111","volume":"83","author":[{"given":"Yun","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Helmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(03)00093-4"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01859-07"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.039"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00476-08"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05131.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.22.6123-6129.2002"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.4.1136-1146.2004"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03050.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2007.09.008"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.07.017"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1915010"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07335.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00267940"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-291"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00443-06"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.2.484-490.2004"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002217"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00611-08"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05360-11"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01230-10"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.06090.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04506.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/9781555817992.ch4"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05598.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06262.x"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.21.6.950"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.9.1160"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510013103"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00286-11"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06023-11"},{"key":"e_1_2_5_32_1","first-page":"516","article-title":"Aztreonam, a new monobactam antimicrobial","volume":"4","author":"Guay D.R.","year":"1985","journal-title":"Clin Pharm"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175439"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01329-08"},{"key":"e_1_2_5_35_1","volume-title":"Molecular Biological Methods for Bacillus","author":"Harwood C.R.","year":"1990"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2911(02)46002-X"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05467-11"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1765"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.9.2915-2921.1997"},{"key":"e_1_2_5_40_1","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1128\/JB.180.15.3765-3770.1998","article-title":"Promoter recognition by Bacillus subtilis \u03c3W: autoregulation and partial overlap with the \u03c3X regulon","volume":"180","author":"Huang X.","year":"1998","journal-title":"J Bacteriol"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.7.2588-2594.2004"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00130-07"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06601.x"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.358"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03875.x"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2333"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04736.x"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07742"},{"key":"e_1_2_5_50_1","article-title":"Glutamate dehydrogenase affects resistance to cell wall antibiotics in Bacillus subtilis","author":"Lee Y.H.","year":"2012","journal-title":"J Bacteriol"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1136611"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00549-09"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00826-10"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2006.00024.x"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.3.749-752.1998"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03786.x"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00904-07"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-137-4-929"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03652.x"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-010-0630-4"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00618-09"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.17.4555-4563.1998"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02639.x"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.13.3664-3670.2002"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235180100"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.77"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00194-06"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4060-9"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.2.326-335.1995"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.6.1921-1927.2001"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.22.6573-6578.2001"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.040238"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01364-10"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.133pe39"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00691-09"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1266\/ggs.84.253"},{"key":"e_1_2_5_77_1","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J.","year":"2001"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.69.4.585-607.2005"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03854.x"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01497-08"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-146-2-249"},{"key":"e_1_2_5_82_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S1016-8478(23)13181-5","article-title":"Identification of essential genes in Streptococcus pneumoniae by allelic replacement mutagenesis","volume":"19","author":"Song J.H.","year":"2005","journal-title":"Mol Cells"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01081-07"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.12.3491-3498.2003"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.06.007"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro727"},{"key":"e_1_2_5_87_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.52.070183.004141"},{"key":"e_1_2_5_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2005.08.016"},{"key":"e_1_2_5_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.02.020"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189801"},{"key":"e_1_2_5_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-128"},{"key":"e_1_2_5_92_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.5.1124"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.091208.073241"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2958.2011.07953.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2958.2011.07953.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T20:15:12Z","timestamp":1713298512000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2958.2011.07953.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,4]]},"references-count":92,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["10.1111\/j.1365-2958.2011.07953.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2958.2011.07953.x","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,4]]}}}