{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:02:35Z","timestamp":1781766155190,"version":"3.54.5"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"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":[[2006,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n            has two porins, PIA and PIB, whose genes (\n            <jats:italic>porA<\/jats:italic>\n            and\n            <jats:italic>porB<\/jats:italic>\n            , respectively) are alleles of a single\n            <jats:italic>por<\/jats:italic>\n            locus. We recently demonstrated that\n            <jats:italic>penB<\/jats:italic>\n            mutations at positions 120 and 121 in PIB, which are presumed to reside in loop 3 that forms the pore constriction zone, confer intermediate-level resistance to penicillin and tetracycline (M. Olesky, M. Hobbs, and R. A. Nicholas, Antimicrob. Agents Chemother.\n            <jats:bold>46:<\/jats:bold>\n            2811-2820, 2002). In the present study, we investigated the electrophysiological properties as well as solute and antibiotic permeation rates of recombinant PIB proteins containing\n            <jats:italic>penB<\/jats:italic>\n            mutations (G120K, G120D\/A121D, G120P\/A121P, and G120R\/A121H). In planar lipid bilayers, the predominant conducting state of each porin variant was 30 to 40% of the wild type, even though the anion selectivity and maximum channel conductance of each PIB variant was similar to that of the wild type. Liposome-swelling experiments revealed no significant differences in the permeation of sugars or \u03b2-lactam antibiotics through the wild type or PIB variants. Although these results are seemingly contradictory with the ability of these variants to increase antibiotic resistance, they are consistent with MIC data showing that these porin mutations confer resistance only in strains containing an\n            <jats:italic>mtrR<\/jats:italic>\n            mutation, which increases expression of the MtrC-MtrD-MtrE efflux pump. Moreover, both the\n            <jats:italic>mtrR<\/jats:italic>\n            and\n            <jats:italic>penB<\/jats:italic>\n            mutations were required to decrease in vivo permeation rates below those observed in the parental strain containing either\n            <jats:italic>mtrR<\/jats:italic>\n            or porin mutations alone. Thus, these data demonstrate a novel mechanism of porin-mediated resistance in which mutations in PIB have no affect on antibiotic permeation alone but instead act synergistically with the MtrC-MtrD-MtrE efflux pump in the development of antibiotic resistance in gonococci.\n          <\/jats:p>","DOI":"10.1128\/jb.188.7.2300-2308.2006","type":"journal-article","created":{"date-parts":[[2006,3,17]],"date-time":"2006-03-17T09:27:51Z","timestamp":1142587671000},"page":"2300-2308","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":135,"title":["Porin-Mediated Antibiotic Resistance in\n            <i>Neisseria gonorrhoeae<\/i>\n            : Ion, Solute, and Antibiotic Permeation through PIB Proteins with\n            <i>penB<\/i>\n            Mutations"],"prefix":"10.1128","volume":"188","author":[{"given":"Melanie","family":"Olesky","sequence":"first","affiliation":[{"name":"Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The 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":"Department of Pharmacology, The 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":"crossref","first-page":"16393","DOI":"10.1016\/S0021-9258(19)84719-1","volume":"264","year":"1989","unstructured":"Bauer, K., M. 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