{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:35:42Z","timestamp":1792737342627,"version":"4.5.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":["Infect Immun"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The genomic analysis of<jats:italic>Streptococcus<\/jats:italic><jats:italic>pneumoniae<\/jats:italic>predicted six putative glutamine uptake systems, which are expressed under<jats:italic>in<\/jats:italic><jats:italic>vitro<\/jats:italic>conditions, as shown here by reverse transcription-PCR. Four of these operons consist of<jats:italic>glnHPQ<\/jats:italic>, while two lack<jats:italic>glnH<\/jats:italic>, which encodes a soluble glutamine-binding protein. Here, we studied the impact of two of these glutamine ATP-binding cassette transporters on<jats:italic>S<\/jats:italic>.<jats:italic>pneumoniae<\/jats:italic>D39 virulence and phagocytosis, which consist of GlnQ and a translationally fused protein of GlnH and GlnP. Mice infected intranasally with D39\u0394<jats:italic>gln0411<\/jats:italic>\/<jats:italic>0412<\/jats:italic>showed significantly increased survival times and a significant delay in the development of pneumococcal pneumonia compared to those infected with D39, as observed in real time using bioluminescent pneumococci. In a mouse sepsis model, the mutant D39\u0394<jats:italic>gln0411<\/jats:italic>\/<jats:italic>0412<\/jats:italic>showed only moderate but significant attenuation. In contrast, the D39\u0394<jats:italic>gln1098<\/jats:italic>\/<jats:italic>1099<\/jats:italic>knockout strain was massively attenuated in the pneumonia and septicemia mouse infection model. To cause pneumonia or sepsis with D39\u0394<jats:italic>gln1098<\/jats:italic>\/<jats:italic>1099<\/jats:italic>, infection doses 100- to 10,000-fold higher than those used for wild-type strain D39 were required. In an experimental mouse meningitis model, D39\u0394<jats:italic>gln1098<\/jats:italic>\/<jats:italic>1099<\/jats:italic>produced decreased levels of white blood cells in cerebrospinal fluid and showed decreased numbers of bacteria in the bloodstream compared to D39 and D39\u0394<jats:italic>gln0411<\/jats:italic>\/<jats:italic>0412<\/jats:italic>. Phagocytosis experiments revealed significantly decreased intracellular survival rates of mutants D39\u0394<jats:italic>gln1098<\/jats:italic>\/<jats:italic>1099<\/jats:italic>and D39\u0394<jats:italic>gln0411<\/jats:italic>\/<jats:italic>0412<\/jats:italic>compared to wild-type D39, suggesting that the deficiency of Gln uptake systems impairs resistance to oxidative stress. Taken together, our results demonstrate that both glutamine uptake systems are required for full virulence of pneumococci but exhibit different impacts on the pathogenesis of pneumococci under<jats:italic>in<\/jats:italic><jats:italic>vivo<\/jats:italic>conditions.<\/jats:p>","DOI":"10.1128\/iai.00855-10","type":"journal-article","created":{"date-parts":[[2010,11,16]],"date-time":"2010-11-16T05:57:00Z","timestamp":1289887020000},"page":"44-58","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Impact of Glutamine Transporters on Pneumococcal Fitness under Infection-Related Conditions"],"prefix":"10.1128","volume":"79","author":[{"given":"Tobias","family":"Ha\u0308rtel","sequence":"first","affiliation":[{"name":"Department of Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt Universita\u0308t Greifswald, D-17487 Greifswald, Germany"},{"name":"Max von Pettenkofer Institute, Ludwig Maximilians Universita\u0308t Mu\u0308nchen, D-80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum Gro\u00dfhadern, Ludwig Maximilians Universita\u0308t Mu\u0308nchen, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Koedel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum Gro\u00dfhadern, Ludwig Maximilians Universita\u0308t Mu\u0308nchen, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Rohde","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, Helmholtz Center of Infection Research, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Petruschka","sequence":"additional","affiliation":[{"name":"Department of Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt Universita\u0308t Greifswald, D-17487 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Department of Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt Universita\u0308t Greifswald, D-17487 Greifswald, Germany"},{"name":"Max von Pettenkofer Institute, Ludwig Maximilians Universita\u0308t Mu\u0308nchen, D-80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1997.0150"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28610-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2416-2419.2004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03557.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02414.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.11.6702-6706.2001"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-001-0907-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.026765-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01333.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2005.11.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5848"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1683-1687.1999"},{"key":"e_1_3_3_14_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1046\/j.1365-2958.2000.01897.x","volume":"36","year":"2000","unstructured":"Hammerschmidt, S., M. 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