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Screening a library of mutants in pneumococcal surface proteins for the ability to survive 10\u2003\u00d7 minimum inhibitory concentration (MIC) of penicillin revealed over 10 candidate tolerance genes. One such mutant contained an insertion in the known gene<jats:italic>psaA<\/jats:italic>, which is part of the<jats:italic>psa<\/jats:italic>locus. This locus encodes an ABC\u2010type Mn permease complex. Sequence analysis of adjacent DNA extended the known genetic organization of the locus to include two new open reading frames (ORFs),<jats:italic>psaB<\/jats:italic>, which encodes an ATP\u2010binding protein, and<jats:italic>psaC<\/jats:italic>, which encodes a hydrophobic transmembrane protein. Mutagenesis of<jats:italic>psaB<\/jats:italic>,<jats:italic>psaC<\/jats:italic>,<jats:italic>psaA<\/jats:italic>and downstream<jats:italic>psaD<\/jats:italic>resulted in penicillin tolerance. Defective adhesion and reduced transformation efficiency, as reported previously for a<jats:italic>psaA<\/jats:italic><jats:sup>\u2212<\/jats:sup>mutant, were phenotypes shared by<jats:italic>psaB<\/jats:italic>\u2003<jats:sup>\u2212<\/jats:sup>,<jats:italic>psaC<\/jats:italic>\u2003<jats:sup>\u2212<\/jats:sup>and<jats:italic>psaD<\/jats:italic>\u2003<jats:sup>\u2212<\/jats:sup>knockout mutants. Western blot analysis demonstrated that the set of mutants expressed RecA, but none of them showed translation of the autolysin gene, which is located downstream of<jats:italic>recA<\/jats:italic>. The addition of manganese (Mn) failed to correct the abnormal physiology. These results suggest that this ABC\u2010type Mn permease complex has a pleiotropic effect on pneumococcal physiology including adherence and autolysis. These are the first genes suggested as being involved in triggering autolysin. The results raise the possibility that loss of function of PsaA, by vaccine\u2010induced antibody for instance, may promote penicillin tolerance.<\/jats:p>","DOI":"10.1046\/j.1365-2958.1998.01016.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:19:39Z","timestamp":1047467979000},"page":"1285-1296","source":"Crossref","is-referenced-by-count":103,"title":["Penicillin tolerance genes of<i>Streptococcus pneumoniae<\/i>: the ABC\u2010type manganese permease complex Psa"],"prefix":"10.1111","volume":"29","author":[{"given":"Rodger","family":"Novak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann S.","family":"Braun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Charpentier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine","family":"Tuomanen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,5]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1990.tb00632.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1472"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(05)80008-7"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.61.3.981-987.1993"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07176.x"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.64.12.5255-5262.1996"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1979.tb03283.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00737.x"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.19.5610-5614.1996"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(87)90278-2"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.7.2493-2498.1995"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb03928.x"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-2508(97)87643-7"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.5111879.x"},{"key":"e_1_2_7_17_2","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1128\/iai.57.11.3527-3533.1989","article-title":"Nucleotide sequence analysis of type 1 fimbrial gene of Streptococcus sanguis FW213","volume":"57","author":"Fenno J.C.","year":"1989","journal-title":"Infect Immun"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02355.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1990.tb02072.x"},{"key":"e_1_2_7_20_2","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1128\/iai.59.3.1093-1099.1991","article-title":"Nucleotide sequence of a gene coding for a saliva\u2010binding protein (SsaB) from Streptococcus sanguis 12 and possible role of the protein in coaggregation with actinomyces","volume":"59","author":"Ganeshkumar N.","year":"1991","journal-title":"Infect Immun"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(86)90215-5"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1988.tb03284.x"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.142.1.90-98.1980"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/7.3.368"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.11140"},{"key":"e_1_2_7_26_2","doi-asserted-by":"crossref","unstructured":"Hayashi S.&Wu H.C.(1992) Identification and characterization of lipid\u2010modified proteins in bacteria. 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