{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:38:34Z","timestamp":1790768314339,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2002,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Chromosomally mediated penicillin resistance in\n            <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n            occurs in part through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. However, the genetic and molecular mechanisms of transformation of a penicillin-susceptible strain of\n            <jats:italic>N. gonorrhoeae<\/jats:italic>\n            to high-level penicillin resistance have not been clearly elucidated. Previous studies suggested that alterations in PBP 1 were involved in high-level penicillin resistance. In this study, we identified a single amino acid mutation in PBP 1 located 40 amino acids N terminal to the active-site serine residue that was present in all chromosomally mediated resistant\n            <jats:italic>N. gonorrhoeae<\/jats:italic>\n            (CMRNG) strains for which MICs of penicillin were \u22651 \u03bcg\/ml. PBP 1 harboring this point mutation (PBP 1*) had a three- to fourfold lower rate of acylation (\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>2<\/jats:sub>\n            \/\n            <jats:italic>K'<\/jats:italic>\n            ) than wild-type PBP 1 with a variety of \u03b2-lactam antibiotics. Consistent with its involvement in high-level penicillin resistance, replacement of the altered\n            <jats:italic>ponA<\/jats:italic>\n            gene (\n            <jats:italic>ponA1<\/jats:italic>\n            ) in several CMRNG strains with the wild-type\n            <jats:italic>ponA<\/jats:italic>\n            gene resulted in a twofold decrease in the MICs of penicillin. Surprisingly, transformation of an intermediate-level penicillin-resistant strain (PR100; FA19\n            <jats:italic>penA4 mtr penB5<\/jats:italic>\n            ) with the\n            <jats:italic>ponA1<\/jats:italic>\n            gene did not increase the MIC of penicillin for this strain. However, we identified an additional resistance locus, termed\n            <jats:italic>penC<\/jats:italic>\n            , which was required along with\n            <jats:italic>ponA1<\/jats:italic>\n            to increase penicillin resistance of PR100 to a high level (MIC = 4 \u03bcg\/ml). The\n            <jats:italic>penC<\/jats:italic>\n            locus by itself, when present in PR100, increases the MICs of penicillin and tetracycline twofold each. These data indicate that an additional locus,\n            <jats:italic>penC<\/jats:italic>\n            , is required along with\n            <jats:italic>ponA1<\/jats:italic>\n            to achieve high-level penicillin resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.46.3.769-777.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:56:57Z","timestamp":1027763817000},"page":"769-777","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":175,"title":["Mutations in\n            <i>ponA<\/i>\n            , the Gene Encoding Penicillin-Binding Protein 1, and a Novel Locus,\n            <i>penC<\/i>\n            , Are Required for High-Level Chromosomally Mediated Penicillin Resistance in\n            <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1128","volume":"46","author":[{"given":"Patricia A.","family":"Ropp","sequence":"first","affiliation":[{"name":"Departments of Chemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Hu","sequence":"additional","affiliation":[{"name":"Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Olesky","sequence":"additional","affiliation":[{"name":"Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.19.2.316"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/jlcr.2580270406","volume":"27","year":"1989","unstructured":"Blaszczak, L. C., N. G. Halligan, and D. E. Seitz. 1989. Radioiododestannylation. Convenient synthesis of a stable penicillin derivative for rapid penicillin binding protein (PBP) assay. J. Label. Compd. Radiopharm.27:401-406.","journal-title":"J. Label. Compd. Radiopharm."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.2.333-337.1994"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1990.tb00664.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.52.2.529-533.1986"},{"key":"e_1_3_2_7_2","unstructured":"Division of STD Prevention. 1998. Sexually Transmitted Disease Surveillance. Supplement: Gonococcal Isolate Surveillance Project (GISP) Annual Report-1998. Department of Health and Human Services Public Health Service. Centers for Disease Control and Prevention Atlanta Ga."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.5.649"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.18.5.730"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1989.tb00108.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1989.tb00101.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.6.856"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009820"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1975.tb02308.x"},{"key":"e_1_3_2_15_2","first-page":"148","year":"1992","unstructured":"Frere, J. M., M. Nguyen-Disteche, J. Coyette, and B. Joris. 1992. Mode of action: interaction with the penicillin binding proteins., p. 148-196. In M. I. Page (ed.), The chemistry of \u03b2-lactams. Chapman & Hall, Glasgow, United Kingdom.","journal-title":"The chemistry of \u03b2-lactams"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.2799"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.4.829"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-141-3-611"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.17.5574-5577.1994"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/314608"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.85.6.1274-1279.1963"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.3.321"},{"key":"e_1_3_2_23_2","first-page":"923","volume":"254","year":"1988","unstructured":"Martin, M. T., and S. G. Waley. 1988. Kinetic characterization of the acyl-enzyme mechanism for \u03b2-lactamase I. Biochem. J.254:923-925.","journal-title":"Kinetic characterization of the acyl-enzyme mechanism for \u03b2-lactamase I. Biochem. J."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(84)90059-3"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.8.2783-2787.1997"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.120.3.1284-1292.1974"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/1046-5928(91)90092-W","volume":"2","year":"1991","unstructured":"Schultz, D. E., B. G. Spratt, and R. A. Nicholas. 1991. Expression and purification of a soluble form of penicillin-binding protein 2 from both penicillin-susceptible and penicillin-resistant Neisseria gonorrhoeae. Protein Expr. Purif.2:339-349.","journal-title":"Protein Expr. 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