Regulation of the arginine deiminase system by argr2 interferes with arginine metabolism and fitness of streptococcus pneumoniae

mBio

Volumn 5, Issue 6, 2014, Pages

  Schulz, Christian ^a   Gierok, Philipp ^a   Petruschka, Lothar ^a   Lalk, Michael ^a   Mäder, Ulrike ^b   Hammerschmidt, Sven ^a  

^a UNIVERSITY OF GREIFSWALD   (Germany)

^b UNIVERSITY MEDICINE GREIFSWALD   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE DEIMINASE; ARGININE ORNITHINE ANTIPORTER; CHLORAMPHENICOL; ERYTHROMYCIN; KANAMYCIN; MEMBRANE PROTEIN; UNCLASSIFIED DRUG; ARGININE; ARGR PROTEIN, BACTERIA; BACTERIAL DNA; BACTERIAL PROTEIN; HYDROLASE; PROTEIN BINDING; REPRESSOR PROTEIN;

AMINO ACID METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ARCABCDT GENE; ARGR2 GENE; ARTICLE; BACTERIAL GENE; CONTROLLED STUDY; GENE DELETION; GENE MUTATION; HUMAN; HUMAN CELL; IN VIVO STUDY; LOBAR PNEUMONIA; MIXED INFECTION; MOUSE; NONHUMAN; NOSE INFECTION; PROMOTER REGION; PROTEIN EXPRESSION; REGULATORY MECHANISM; RESPIRATORY SYSTEM; STREPTOCOCCUS PNEUMONIAE; ANIMAL; BIOSYNTHESIS; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MICROBIOLOGY; MULTIGENE FAMILY; PATHOLOGY; PHYSIOLOGY; PNEUMOCOCCAL INFECTION; VIRULENCE;

MUS; STREPTOCOCCUS PNEUMONIAE;

ANIMALS; ARGININE; BACTERIAL PROTEINS; DISEASE MODELS, ANIMAL; DNA, BACTERIAL; GENE DELETION; GENE EXPRESSION REGULATION, BACTERIAL; HYDROLASES; MICE; MULTIGENE FAMILY; PNEUMOCOCCAL INFECTIONS; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; REPRESSOR PROTEINS; STREPTOCOCCUS PNEUMONIAE; VIRULENCE;

EID: 84920996729     PISSN: 21612129     EISSN: 21507511     Source Type: Journal    
DOI: 10.1128/mBio.01858-14     Document Type: Article

References (78)

1. Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rümke HC, Verbrugh HA, Hermans PW. 2004. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 363: 1871–1872. http://dx.doi.org/10.1016/S0140-6736(04)16357-5.
2. Cartwright K. 2002. Pneumococcal disease in Western Europe: burden of disease, antibiotic resistance and management. Eur. J. Pediatr. 161: 188–195. http://dx.doi.org/10.1007/s00431-001-0907-3.
3. Musher DM. 1992. Infections caused by Streptococcus pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin. Infect. Dis. 14:801–807. http://dx.doi.org/10.1093/clinids/14.4.801.
4. Gamez G, Hammerschmidt S. 2012. Combat pneumococcal infections: adhesins as candidates for protein-based vaccine development. Curr. Drug Targets 13:323–337. http://dx.doi.org/10.2174/ 138945012799424697.
5. Paterson GK, Mitchell TJ. 2006. Innate immunity and the pneumococcus. Microbiology 152:285–293. http://dx.doi.org/10.1099/ mic.0.28551-0.
6. Härtel T, Eylert E, Schulz C, Petruschka L, Gierok P, Grubmüller S, Lalk M, Eisenreich W, Hammerschmidt S. 2012. Characterization of central carbon metabolism of Streptococcus pneumoniae by isotopologue profiling. J. Biol. Chem. 287:4260-4274. http://dx.doi.org/10.1074/ jbc.M111.304311.
7. Härtel T, Klein M, Koedel U, Rohde M, Petruschka L, Hammerschmidt S. 2011. Impact of glutamine transporters on pneumococcal fitness under infection-related conditions. Infect. Immun. 79:44–58. http://dx.doi.org/ 10.1128/IAI.00855-10.
8. Canepa A, Filho JC, Gutierrez A, Carrea A, Forsberg AM, Nilsson E, Verrina E, Perfumo F, Bergström J. 2002. Free amino acids in plasma, red blood cells, polymorphonuclear leukocytes, and muscle in normal and uraemic children. Nephrol. Dial. Transplant. 17:413-421. http:// dx.doi.org/10.1093/ndt/17.3.413.
9. Sethuraman R, Lee TL, Chui JW, Tachibana S. 2006. Changes in amino acids and nitric oxide concentration in cerebrospinal fluid during labor pain. Neurochem. Res. 31:1127–1133. http://dx.doi.org/10.1007/s11064- 006-9133-8.
10. Currie GA, Gyure L, Cifuentes L. 1979. Microenvironmental arginine depletion by macrophages in vivo. Br. J. Cancer 39:613-620. http:// dx.doi.org/10.1038/bjc.1979.112.
11. Albina JE, Mills CD, Barbul A, Thirkill CE, Henry WL, Mastrofrancesco B, Caldwell MD. 1988. Arginine metabolism in wounds. Am. J. Physiol. 254:E459–E467.
12. Wu G. 2009. Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17. http://dx.doi.org/10.1007/s00726-009-0269-0.
13. Li P, Yin YL, Li D, Kim SW, Wu G. 2007. Amino acids and immune function. Br. J. Nutr. 98:237–252. http://dx.doi.org/10.1017/ S000711450769936X.
14. Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA, 1998. The natural polyamine spermine functions directly as a free radical scavenger. Proc. Natl. Acad. Sci. U. S. A. 95:11140–11145. http:// dx.doi.org/10.1073/pnas.95.19.11140.
15. Chattopadhyay MK, Tabor CW, Tabor H. 2003. Polyamines protect Escherichia coli cells from the toxic effect of oxygen. Proc. Natl. Acad. Sci. U. S. A. 100:2261–2265. http://dx.doi.org/10.1073/pnas.2627990100.
16. Piet JR, Geldhoff M, van Schaik BD, Brouwer MC, Valls Seron M, Jakobs ME, Schipper K, Pannekoek Y, Zwinderman AH, van der Poll T, van Kampen AH, Baas F, van der Ende A, van de Beek D. 2014. Streptococcus pneumoniae arginine synthesis genes promote growth and virulence in pneumococcal meningitis. J. Infect. Dis. 209:1781–1791. http://dx.doi.org/10.1093/infdis/jit818.
17. Abdelal AT. 1979. Arginine catabolism by microorganisms. Annu. Rev. Microbiol. 33:139-168. http://dx.doi.org/10.1146/ annurev.mi.33.100179.001035.
18. Blakemore RP, Canale-Parola E. 1976. Arginine catabolism by Treponema denticola. J. Bacteriol. 128:616–622.
19. Broman K, Lauwers N, Stalon V, Wiame JM. 1978. Oxygen and nitrate in utilization by Bacillus licheniformis of the arginase and arginine deiminase routes of arginine catabolism and other factors affecting their syntheses. J. Bacteriol. 135:920–927.
20. Floderus E, Linder LE, Sund ML. 1990. Arginine catabolism by strains of oral streptococci. APMIS 98:1045–1052. http://dx.doi.org/10.1111/ j.1699-0463.1990.tb05033.x.
21. Mercenier A, Simon JP, Haas D, Stalon V. 1980. Catabolism of L-arginine by Pseudomonas aeruginosa. J. Gen. Microbiol. 116:381–389.
22. Burne RA, Marquis RE. 2000. Alkali production by oral bacteria and protection against dental caries. FEMS Microbiol. Lett. 193:1–6. http:// dx.doi.org/10.1111/j.1574-6968.2000.tb09393.x.
23. Dong Y, Chen YY, Snyder JA, Burne RA. 2002. Isolation and molecular analysis of the gene cluster for the arginine deiminase system from Streptococcus gordonii DL1. Appl. Environ. Microbiol. 68:5549–5553. http:// dx.doi.org/10.1128/AEM.68.11.5549-5553.2002.
24. Griswold A, Chen YY, Snyder JA, Burne RA. 2004. Characterization of the arginine deiminase operon of Streptococcus rattus FA-1. Appl. Environ. Microbiol. 70:1321–1327. http://dx.doi.org/10.1128/AEM.70.3.1321- 1327.2004.
25. Gruening P, Fulde M, Valentin-Weigand P, Goethe R. 2006. Structure, regulation, and putative function of the arginine deiminase system of Streptococcus suis. J. Bacteriol. 188:361–369. http://dx.doi.org/10.1128/ JB.188.2.361-369.2006.
26. Maghnouj A, de Sousa Cabral TF, Stalon V, Vander Wauven C. 1998. The arcABDC gene cluster, encoding the arginine deiminase pathway of Bacillus licheniformis, and its activation by the arginine repressor ArgR. J. Bacteriol. 180:6468–6475.
27. Vander Wauven C, Piérard A, Kley-Raymann M, Haas D. 1984. Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway. J. Bacteriol. 160:928–934.
28. Zúñiga M, Pérez G, González-Candelas F. 2002. Evolution of arginine deiminase (ADI) pathway genes. Mol. Phylogenet. Evol. 25:429–444. http://dx.doi.org/10.1016/S1055-7903(02)00277-4.
29. Poolman B. 1993. Energy transduction in lactic acid bacteria. FEMS Microbiol. Rev. 12:125–147. http://dx.doi.org/10.1111/j.1574- 6976.1993.tb00015.x.
30. Wimmer F, Oberwinkler T, Bisle B, Tittor J, Oesterhelt D. 2008. Identification of the arginine/ornithine antiporter ArcD from Halobacterium salinarum. FEBS Lett. 582:3771–3775. http://dx.doi.org/10.1016/ j.febslet.2008.10.004.
31. Casiano-Colón A, Marquis RE. 1988. Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance. Appl. Environ. Microbiol. 54:1318–1324.
32. Nascimento MM, Gordan VV, Garvan CW, Browngardt CM, Burne RA. 2009. Correlations of oral bacterial arginine and urea catabolism with caries experience. Oral Microbiol. Immunol. 24:89–95. http://dx.doi.org/ 10.1111/j.1399-302X.2008.00477.x.
33. Hogardt M, Heesemann J. 2010. Adaptation of Pseudomonas aeruginosa during persistence in the cystic fibrosis lung. Int. J. Med. Microbiol. 300: 557–562. http://dx.doi.org/10.1016/j.ijmm.2010.08.008.
34. Winterhoff N, Goethe R, Gruening P, Rohde M, Kalisz H, Smith HE, Valentin-Weigand P. 2002. Identification and characterization of two temperature-induced surface-associated proteins of Streptococcus suis with high homologies to members of the arginine deiminase system of Streptococcus pyogenes. J. Bacteriol. 184:6768–6776. http://dx.doi.org/ 10.1128/JB.184.24.6768-6776.2002.
35. Gupta R, Yang J, Dong Y, Swiatlo E, Zhang JR, Metzger DW, Bai G. 2013. Deletion of arcD in Streptococcus pneumoniae D39 impairs its capsule and attenuates virulence. Infect. Immun. 81:3903–3911. http:// dx.doi.org/10.1128/IAI.00778-13.
36. Lu CD, Winteler H, Abdelal A, Haas D. 1999. The ArgR regulatory protein, a helper to the anaerobic regulator ANR during transcriptional activation of the arcD promoter in Pseudomonas aeruginosa. J. Bacteriol. 181:2459–2464.
37. Dong Y, Chen YY, Burne RA. 2004. Control of expression of the arginine deiminase operon of Streptococcus gordonii by CcpA and Flp. J. Bacteriol. 186:2511–2514. http://dx.doi.org/10.1128/JB.186.8.2511-2514.2004.
38. Barcelona-Andrés B, Marina A, Rubio V. 2002. Gene structure, organization, expression, and potential regulatory mechanisms of arginine catabolism in Enterococcus faecalis. J. Bacteriol. 184:6289-6300. http:// dx.doi.org/10.1128/JB.184.22.6289-6300.2002.
39. Maghnouj A, Abu-Bakr AA, Baumberg S, Stalon V, Vander Wauven C. 2000. Regulation of anaerobic arginine catabolism in Bacillus licheniformis by a protein of the Crp/Fnr family. FEMS Microbiol. Lett. 191:227–234. http://dx.doi.org/10.1111/j.1574-6968.2000.tb09344.x.
40. Makhlin J, Kofman T, Borovok I, Kohler C, Engelmann S, Cohen G, Aharonowitz Y. 2007. Staphylococcus aureus ArcR controls expression of the arginine deiminase operon. J. Bacteriol. 189:5976-5986. http:// dx.doi.org/10.1128/JB.00592-07.
41. Ferro KJ, Bender GR, Marquis RE. 1983. Coordinately repressible arginine deiminase system in Streptococcus sanguis. Curr. Microbiol. 9:145–149. http://dx.doi.org/10.1007/BF01567287.
42. Fulde M, Willenborg J, de Greeff A, Benga L, Smith HE, Valentin- Weigand P, Goethe R. 2011. ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment. Microbiology 157:572–582. http://dx.doi.org/10.1099/mic.0.043067-0.
43. Baumberg S, Klingel U. 1993. Biosynthesis of arginine, proline and related compounds, p 299572–306. In Sonenshein AL, Hoch JA, Losick R (ed), Bacillus subtilis and other Gram-positive bacteria. American Society for Microbiology, Washington, DC.
44. Kloosterman TG, Kuipers OP. 2011. Regulation of arginine acquisition and virulence gene expression in the human pathogen Streptococcus pneumoniae by transcription regulators ArgR1 and AhrC. J. Biol. Chem. 286: 44594–44605. http://dx.doi.org/10.1074/jbc.M111.295832.
45. Lanie JA, Ng WL, Kazmierczak KM, Andrzejewski TM, Davidsen TM, Wayne KJ, Tettelin H, Glass JI, Winkler ME. 2007. Genome sequence of Avery’s virulent serotype 2 strain D39 of Streptococcus pneumoniae and comparison with that of unencapsulated laboratory strain R6. J. Bacteriol. 189:38–51. http://dx.doi.org/10.1128/JB.01148-06.
46. Knodler LA, Sekyere EO, Stewart TS, Schofield PJ, Edwards MR. 1998. Cloning and expression of a prokaryotic enzyme, arginine deiminase, from a primitive eukaryote Giardia intestinalis. J. Biol. Chem. 273: 4470–4477. http://dx.doi.org/10.1074/jbc.273.8.4470.
47. Houghton JE, Bencini DA, O’Donovan GA, Wild JR. 1984. Protein differentiation: a comparison of aspartate transcarbamoylase and ornithine transcarbamoylase from Escherichia coli K-12. Proc. Natl. Acad. Sci. U. S. A. 81:4864–4868. http://dx.doi.org/10.1073/pnas.81.15.4864.
48. Marina A, Uriarte M, Barcelona B, Fresquet V, Cervera J, Rubio V. 1998. Carbamate kinase from Enterococcus faecalis and Enterococcus faecium— cloning of the genes, studies on the enzyme expressed in Escherichia coli, and sequence similarity with N-acetyl-L-glutamate kinase. Eur. J. Biochem. 253:280-291. http://dx.doi.org/10.1046/j.1432-1327.1998.2530280.x.
49. Degnan BA, Fontaine MC, Doebereiner AH, Lee JJ, Mastroeni P, Dougan G, Goodacre JA, Kehoe MA. 2000. Characterization of an isogenic mutant of Streptococcus pyogenes Manfredo lacking the ability to make streptococcal acid glycoprotein. Infect. Immun. 68:2441–2448. http://dx.doi.org/10.1128/IAI.68.5.2441-2448.2000.
50. Ryan S, Begley M, Gahan CG, Hill C. 2009. Molecular characterization of the arginine deiminase system in Listeria monocytogenes: regulation and role in acid tolerance. Environ. Microbiol. 11:432–445. http://dx.doi.org/ 10.1111/j.1462-2920.2008.01782.x.
51. Larsen R, Buist G, Kuipers OP, Kok J. 2004. ArgR and AhrC are both required for regulation of arginine metabolism in Lactococcus lactis. J. Bacteriol. 186:1147–1157. http://dx.doi.org/10.1128/JB.186.4.1147-1157.2004.
52. Larsen R, Kok J, Kuipers OP. 2005. Interaction between ArgR and AhrC controls regulation of arginine metabolism in Lactococcus lactis. J. Biol. Chem. 280:19319–19330. http://dx.doi.org/10.1074/jbc.M413983200.
53. Larsen R, van Hijum SA, Martinussen J, Kuipers OP, Kok J. 2008. Transcriptome analysis of the Lactococcus lactis ArgR and AhrC regulons. Appl. Environ. Microbiol. 74:4768-4771. http://dx.doi.org/10.1128/AEM.00117-08.
54. Maas WK. 1994. The arginine repressor of Escherichia coli. Microbiol. Rev. 58:631–640.
55. Park SM, Lu CD, Abdelal AT. 1997. Purification and characterization of an arginine regulatory protein, ArgR, from Pseudomonas aeruginosa and its interactions with the control regions for the car, argF, and aru operons. J. Bacteriol. 179:5309–5317.
56. Park SM, Lu CD, Abdelal AT. 1997. Cloning and characterization of argR, a gene that participates in regulation of arginine biosynthesis and catabolism in Pseudomonas aeruginosa PAO1. J. Bacteriol. 179: 5300–5308.
57. Dennis C CA, Glykos NM, Parsons MR, Phillips SE. 2002. The structure of AhrC, the arginine repressor/activator protein from Bacillus subtilis. Acta Crystallogr. D Biol. Crystallogr. 58:421-430. http://dx.doi.org/ 10.1107/S0907444901021692.
58. Miller CM, Baumberg S, Stockley PG. 1997. Operator interactions by the Bacillus subtilis arginine repressor/activator, AhrC: novel positioning and DNA-mediated assembly of a transcriptional activator at catabolic sites. Mol. Microbiol. 26:37-48. http://dx.doi.org/10.1046/j.1365- 2958.1997.5441907.x.
59. Gardan R, Rapoport G, Débarbouillé M. 1997. Role of the transcriptional activator RocR in the arginine-degradation pathway of Bacillus subtilis. Mol. Microbiol. 24:825-837. http://dx.doi.org/10.1046/j.1365- 2958.1997.3881754.x.
60. Nicoloff H, Arsène-Ploetze F, Malandain C, Kleerebezem M, Bringel F. 2004. Two arginine repressors regulate arginine biosynthesis in Lactobacillus plantarum. J. Bacteriol. 186:6059–6069. http://dx.doi.org/10.1128/ JB.186.18.6059-6069.2004.
61. Cherney LT, Cherney MM, Garen CR, Lu GJ, James MN. 2008. Crystal structure of the arginine repressor protein in complex with the DNA operator from Mycobacterium tuberculosis. J. Mol. Biol. 384:1330-1340. http://dx.doi.org/10.1016/j.jmb.2008.10.015.
62. Garnett JA, Marincs F, Baumberg S, Stockley PG, Phillips SE. 2008. Structure and function of the arginine repressor-operator complex from Bacillus subtilis. J. Mol. Biol. 379:284-298. http://dx.doi.org/10.1016/ j.jmb.2008.03.007.
63. Makarova KS, Mironov AA, Gelfand MS. 2001. Conservation of the binding site for the arginine repressor in all bacterial lineages. Genome Biol. 2:RESEARCH0013. http://dx.doi.org/10.1186/gb-2001-2-4- research0013.
64. Liu Y, Dong Y, Chen YY, Burne RA. 2008. Environmental and growth phase regulation of the Streptococcus gordonii arginine deiminase genes. Appl. Environ. Microbiol. 74:5023–5030. http://dx.doi.org/10.1128/ AEM.00556-08.
65. Carvalho SM, Kloosterman TG, Kuipers OP, Neves AR. 2011. CcpA ensures optimal metabolic fitness of Streptococcus pneumoniae. PLoS One 6:e26707. http://dx.doi.org/10.1371/journal.pone.0026707.
66. Abdullah MR, Gutiérrez-Fernández J, Pribyl T, Gisch N, Saleh M, Rohde M, Petruschka L, Burchhardt G, Schwudke D, Hermoso JA, Hammerschmidt S. 2014. Structure of the pneumococcal L,Dcarboxypeptidase DacB and pathophysiological effects of disabled cell wall hydrolases DacA and DacB. Mol. Microbiol. 93:1183–1206. http:// dx.doi.org/10.1111/mmi.12729.
67. Hitzmann A, Bergmann S, Rohde M, Chhatwal GS, Fulde M. 2013. Identification and characterization of the arginine deiminase system of Streptococcus canis. Vet. Microbiol. 162:270-277. http://dx.doi.org/ 10.1016/j.vetmic.2012.08.004.
68. Jensch I, Gámez G, Rothe M, Ebert S, Fulde M, Somplatzki D, Berg-mann S, Petruschka L, Rohde M, Nau R, Hammerschmidt S. 2010. PavB is a surface-exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections. Mol. Microbiol. 77: 22–43. http://dx.doi.org/10.1111/j.1365-2958.2010.07189.x.
69. Hammerschmidt S, Talay SR, Brandtzaeg P, Chhatwal GS. 1997. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol. Microbiol. 25: 1113–1124. http://dx.doi.org/10.1046/j.1365-2958.1997.5391899.x.
70. Chen JD, Morrison DA. 1988. Construction and properties of a new insertion vector, pJDC9, that is protected by transcriptional terminators and useful for cloning of DNA from Streptococcus pneumoniae. Gene 64: 155–164. http://dx.doi.org/10.1016/0378-1119(88)90489-1.
71. Saleh M, Bartual SG, Abdullah MR, Jensch I, Asmat TM, Petruschka L, Pribyl T, Gellert M, Lillig CH, Antelmann H, Hermoso JA, Hammerschmidt S. 2013. Molecular architecture of Streptococcus pneumoniae surface thioredoxin-fold lipoproteins crucial for extracellular oxidative stress resistance and maintenance of virulence. EMBO. Mol. Med. 5:1852–1870. http://dx.doi.org/10.1002/emmm.201202435.
72. Dörries K, Lalk M. 2013. Metabolic footprint analysis uncovers strain specific overflow metabolism and D-isoleucine production of Staphylococcus aureus COL and HG001. PLoS One 8:e81500. http://dx.doi.org/ 10.1371/journal.pone.0081500.
73. Oginsky EL. 1957. Isolation and determination of arginine and citrulline. Methods Enzymol. 3:639-643. http://dx.doi.org/10.1016/S0076- 6879(57)03434-5.
74. Degnan BA, Palmer JM, Robson T, Jones CE, Fischer M, Glanville M, Mellor GD, Diamond AG, Kehoe MA, Goodacre JA. 1998. Inhibition of human peripheral blood mononuclear cell proliferation by Streptococcus pyogenes cell extract is associated with arginine deiminase activity. Infect. Immun. 66:3050–3058.
75. Saleh M, Abdullah MR, Schulz C, Kohler T, Pribyl T, Jensch I, Hammerschmidt S. 2014. Following in real time the impact of pneumococcal virulence factors in an acute mouse pneumonia model using bioluminescent bacteria. J. Vis. Exp. 2014:e51174. doi: 10.3791/51174.
76. Hermans PW, Adrian PV, Albert C, Estevão S, Hoogenboezem T, Luijendijk IH, Kamphausen T, Hammerschmidt S. 2006. The streptococcal lipoprotein rotamase A (SlrA) is a functional peptidyl-prolyl isomerase involved in pneumococcal colonization. J. Biol. Chem. 281: 968–976. http://dx.doi.org/10.1074/jbc.M510014200.
77. Kerr AR, Irvine JJ, Search JJ, Gingles NA, Kadioglu A, Andrew PW, McPheat WL, Booth CG, Mitchell TJ. 2002. Role of inflammatory mediators in resistance and susceptibility to pneumococcal infection. Infect. Immun. 70:1547–1557. http://dx.doi.org/10.1128/IAI.70.3.1547-1557.2002.
78. Bergmann S, Lang A, Rohde M, Agarwal V, Rennemeier C, Grashoff C, Preissner KT, Hammerschmidt S. 2009. Integrin-linked kinase is required for vitronectin-mediated internalization of Streptococcus pneumoniae by host cells. J. Cell Sci. 122:256–267. http://dx.doi.org/10.1242/ jcs.035600.