{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:11:09Z","timestamp":1791108669717,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2009,2,15]],"date-time":"2009-02-15T00:00:00Z","timestamp":1234656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2009,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            During inhalational anthrax,\n            <jats:italic>Bacillus anthracis<\/jats:italic>\n            survives and replicates in alveolar macrophages, followed by rapid invasion into the host's bloodstream, where it multiplies to cause heavy bacteremia.\n            <jats:italic>B. anthracis<\/jats:italic>\n            must therefore defend itself from host immune functions encountered during both the intracellular and the extracellular stages of anthrax infection. In both of these niches, cationic antimicrobial peptides are an essential component of the host's innate immune response that targets\n            <jats:italic>B. anthracis<\/jats:italic>\n            . However, the genetic determinants of\n            <jats:italic>B. anthracis<\/jats:italic>\n            contributing to resistance to these peptides are largely unknown. Here we generated Tn\n            <jats:italic>917<\/jats:italic>\n            transposon mutants in the \u0394ANR strain (pXO1\n            <jats:sup>\u2212<\/jats:sup>\n            pXO2\n            <jats:sup>\u2212<\/jats:sup>\n            ) of\n            <jats:italic>B. anthracis<\/jats:italic>\n            and screened them for altered protamine susceptibility. A protamine-sensitive mutant identified carried the transposon inserted in the BA1486 gene encoding a putative membrane protein homologous to MprF known in several gram-positive pathogens. A mutant strain with the BAS1375 gene (the orthologue of BA1486) deleted in the Sterne 34F2 strain (pXO1\n            <jats:sup>+<\/jats:sup>\n            pXO2\n            <jats:sup>\u2212<\/jats:sup>\n            ) of\n            <jats:italic>B. anthracis<\/jats:italic>\n            exhibited hypersusceptibility not only to protamine but also to \u03b1-helical cathelicidin LL-37 and \u03b2-sheet defensin human neutrophil peptide 1 compared to the wild-type Sterne strain. Analysis of membrane lipids using isotopic labeling demonstrated that the BAS1375 deletion mutant is unable to synthesize lysinylated phosphatidylglycerols, and this defect is rescued by genetic complementation. Further, we determined the structures of these lysylphosphatidylglycerols by using various mass spectrometric analyses. These results demonstrate that in\n            <jats:italic>B. anthracis<\/jats:italic>\n            a functional MprF is required for the biosynthesis of lysylphosphatidylglycerols, which is critical for resistance to cationic antimicrobial peptides.\n          <\/jats:p>","DOI":"10.1128\/jb.01345-08","type":"journal-article","created":{"date-parts":[[2008,12,13]],"date-time":"2008-12-13T02:48:38Z","timestamp":1229136518000},"page":"1311-1319","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["The\n            <i>Bacillus anthracis<\/i>\n            Protein MprF Is Required for Synthesis of Lysylphosphatidylglycerols and for Resistance to Cationic Antimicrobial Peptides"],"prefix":"10.1128","volume":"191","author":[{"given":"Shalaka","family":"Samant","sequence":"first","affiliation":[{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, M\/C 870, 900 S. Ashland Ave., Chicago, Illinois 60607"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fong-Fu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Resource, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Neyfakh","sequence":"additional","affiliation":[{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, M\/C 870, 900 S. Ashland Ave., Chicago, Illinois 60607"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunwoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, M\/C 870, 900 S. Ashland Ave., Chicago, Illinois 60607"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2958.2002.02723.x","volume":"43","year":"2002","unstructured":"Abachin, E., C. Poyart, E. Pellegrini, E. Milohanic, F. Fiedler, P. Berche, and P. Trieu-Cuot. 2002. Formation of d-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol. Microbiol. 43 : 1-14.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.2.562-567.1999"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.2.872-877.2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.10.6076-6085.2004"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1462-5822.2000.00067.x","volume":"2","year":"2000","unstructured":"Dixon, T. C., A. A. Fadl, T. M. Koehler, J. A. Swanson, and P. C. Hanna. 2000. Early Bacillus anthracis-macrophage interactions: intracellular survival and escape. Cell. Microbiol. 2 : 453-463.","journal-title":"Cell. Microbiol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.4.1301-1309.2006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.21.7280-7289.2004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"11939","DOI":"10.1073\/pnas.89.24.11939","volume":"89","year":"1992","unstructured":"Groisman, E. A., C. Parra-Lopez, M. Salcedo, C. J. Lipps, and F. Heffron. 1992. Resistance to host antimicrobial peptides is necessary for Salmonella virulence. Proc. Natl. Acad. Sci. USA 89 : 11939-11943.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1365-2958.1999.01137.x","volume":"31","year":"1999","unstructured":"Guidi-Rontani, C., M. Weber-Levy, E. Labruy\u00e8re, and M. Mock. 1999. Germination of Bacillus anthracis spores within alveolar macrophages. Mol. Microbiol. 31 : 9-17.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.14.4166-4175.1996"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.8.3091-3099.1997"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/S1044-0305(01)00285-9","volume":"12","year":"2001","unstructured":"Hsu, F.-F., and J. Turk. 2001. Studies on phosphatidylglycerol with triple quadrupole tandem mass spectrometry with electrospray ionization: fragmentation processes and structural characterization. J. Am. Soc. Mass Spectrom. 12 : 1036-1043.","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.jasms.2005.04.018","volume":"16","year":"2005","unstructured":"Hsu, F.-F., and J. Turk. 2005. Studies on phosphatidylserine by tandem quadrupole and multiple stage quadrupole ion-trap mass spectrometry with electrospray ionization: structural characterization and the fragmentation processes. J. Am. Soc. Mass Spectrom. 16 : 1510-1522.","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.48.4.726-731.1984"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00336-06"},{"key":"e_1_3_2_18_2","first-page":"231","volume":"306","year":"2006","unstructured":"Kraus, D., and A. Peschel. 2006. Molecular mechanisms of bacterial resistance to antimicrobial peptides. Curr. Top. Microbiol. Immunol. 306 : 231-250.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1182\/blood.V96.8.2664","volume":"96","year":"2000","unstructured":"Levy, O. 2000. Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents. Blood 96 : 2664-2672.","journal-title":"Blood"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1111\/j.1365-2958.2007.05986.x","volume":"66","year":"2007","unstructured":"Li, M., D. J. Cha, Y. Lai, A. E. Villaruz, D. E. Sturdevant, and M. Otto. 2007. The antimicrobial peptide-sensing system aps of Staphylococcus aureus. Mol. Microbiol. 66 : 1136-1147.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"9469","DOI":"10.1073\/pnas.0702159104","volume":"104","year":"2007","unstructured":"Li, M., Y. Lai, A. E. Villaruz, D. J. Cha, D. E. Sturdevant, and M. Otto. 2007. gram-positive three-component antimicrobial peptide-sensing system. Proc. Natl. Acad. Sci. USA 104 : 9469-9474.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.8.4801-4809.2004"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1111\/j.1365-2958.2005.04776.x","volume":"57","year":"2005","unstructured":"Mandin, P., H. Fsihi, O. Dussurget, M. Vergassola, E. Milohanic, A. Toledo-Arana, I. Lasa, J. Johansson, and P. Cossart. 2005. VirR, a response regulator critical for Listeria monocytogenes virulence. Mol. Microbiol. 57 : 1367-1380.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1371\/journal.ppat.0010023","volume":"1","year":"2005","unstructured":"Mayer-Scholl, A., R. Hurwitz, V. Brinkmann, M. Schmid, P. Jungblut, Y. Weinrauch, and A. Zychlinsky. 2005. Human neutrophils kill Bacillus anthracis. PLoS Pathog. 1 : e23.","journal-title":"PLoS Pathog."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1146\/annurev.micro.55.1.647","volume":"55","year":"2001","unstructured":"Mock, M., and A. Fouet. 2001. Anthrax. Annu. Rev. Microbiol. 55 : 647-671.","journal-title":"Annu. Rev. Microbiol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.12.4800-4807.2004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(99)10008-9"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1099\/mic.0.26706-0","volume":"150","year":"2004","unstructured":"Oku, Y., K. Kurokawa, N. Ichihashi, and K. Sekimizu. 2004. Characterization of the Staphylococcus aureus mprF gene, involved in lysinylation of phosphatidylglycerol. Microbiology 150 : 45-51.","journal-title":"Microbiology"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-1119(94)90597-5","volume":"143","year":"1994","unstructured":"Palmer, B. R., and M. G. Marinus. 1994. The dam and dcm strains of Escherichia coli. Gene 143 : 1-12.","journal-title":"Gene"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1084\/jem.193.9.1067","volume":"193","year":"2001","unstructured":"Peschel, A., R. W. Jack, M. Otto, L. V. Collins, P. Staubitz, G. Nicholson, H. Kalbacher, W. F. Nieuwenhuizen, G. Jung, A. Tarkowski, K. P. van Kessel, and J. A. van Strijp. 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J. Exp. Med. 193 : 1067-1076.","journal-title":"J. Exp. Med."},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"8405","DOI":"10.1074\/jbc.274.13.8405","volume":"274","year":"1999","unstructured":"Peschel, A., M. Otto, R. W. Jack, H. Kalbacher, G. Jung, and F. Gotz. 1999. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J. Biol. Chem. 274 : 8405-8410.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1099\/mic.0.28764-0","volume":"152","year":"2006","unstructured":"Reeve, W. G., L. Brau, J. Castelli, G. Garau, C. Sohlenkamp, O. Geiger, M. J. Dilworth, A. R. Glenn, J. G. Howieson, and R. P. Tiwari. 2006. The Sinorhizobium medicae WSM419 lpiA gene is transcriptionally activated by FsrR and required to enhance survival in lethal acid conditions. Microbiology 152 : 3049-3059.","journal-title":"Microbiology"},{"key":"e_1_3_2_33_2","unstructured":"Molecular cloning: a laboratory manual 2001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.1016\/S0021-9258(18)68615-6","volume":"263","year":"1988","unstructured":"Sekimizu, K., and A. Kornberg. 1988. Cardiolipin activation of dnaA protein, the initiation protein of replication in Escherichia coli. J. Biol. Chem. 263 : 7131-7135.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.femsle.2005.03.029","volume":"245","year":"2005","unstructured":"Shatalin, K. Y., and A. A. Neyfakh. 2005. Efficient gene inactivation in Bacillus anthracis. FEMS Microbiol. Lett. 245 : 315-319.","journal-title":"FEMS Microbiol. Lett."},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1094\/MPMI-20-11-1421","volume":"20","year":"2007","unstructured":"Sohlenkamp, C., K. A. Galindo-Lagunas, Z. Guan, P. Vinuesa, S. Robinson, J. Thomas-Oates, C. R. H. Raetz, and O. Geiger. 2007. The Lipid lysyl-phosphatidylglycerol is present in membranes of Rhizobium tropici CIAT899 and confers increased resistance to polymyxin B under acidic growth conditions. Mol. Plant-Microbe Interact. 20 : 1421-1430.","journal-title":"Mol. Plant-Microbe Interact."},{"key":"e_1_3_2_37_2","first-page":"41","volume":"21","year":"1937","unstructured":"Sterne, M. 1937. Avirulent anthrax vaccine. Onderstepoort J. Vet. Sci. Anim. Ind. 21 : 41-43.","journal-title":"Onderstepoort J. Vet. Sci. Anim. Ind."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/j.1365-2958.2006.05452.x","volume":"62","year":"2006","unstructured":"Thedieck, K., T. Hain, W. Mohamed, B. J. Tindall, M. Nimtz, T. Chakraborty, J. Wehland, and L. Jansch. 2006. The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes. Mol. Microbiol. 62 : 1325-1339.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0378-1119(83)90022-7","volume":"23","year":"1983","unstructured":"Trieu-Cuot, P., and P. Courvalin. 1983. Nucleotide sequence of the Streptococcus faecalis plasmid gene encoding the 3\u20325\u2033-aminoglycoside phosphotransferase type III. Gene 23 : 331-341.","journal-title":"Gene"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1094\/MPMI.2003.16.2.159","volume":"16","year":"2003","unstructured":"Vinuesa, P., F. Neumann-Silkow, C. Pacios-Bras, H. P. Spaink, E. Martinez-Romero, and D. Werner. 2003. Genetic analysis of a pH-regulated operon from Rhizobium tropici CIAT899 involved in acid tolerance and nodulation competitiveness. Mol. Plant-Microbe Interact. 16 : 159-168.","journal-title":"Mol. Plant-Microbe Interact."},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0882-4010(91)90053-D","volume":"10","year":"1991","unstructured":"Welkos, S. L. 1991. Plasmid-associated virulence factors of non-toxigenic (pXO1\u2212) Bacillus anthracis. Microb. Pathog. 10 : 183-198.","journal-title":"Microb. Pathog."},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1124\/pr.55.1.2","volume":"55","year":"2003","unstructured":"Yeaman, M. R., and N. Y. Yount. 2003. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev. 55 : 27-55.","journal-title":"Pharmacol. Rev."}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.01345-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.01345-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T17:11:15Z","timestamp":1627578675000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.01345-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,15]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,2,15]]}},"alternative-id":["10.1128\/JB.01345-08"],"URL":"https:\/\/doi.org\/10.1128\/jb.01345-08","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,15]]},"assertion":[{"value":"2008-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-11-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}