Exploring the metabolic network of the epidemic pathogen Burkholderia cenocepacia J2315 via genome-scale reconstruction

BMC Systems Biology

Volumn 5, Issue , 2011, Pages

  Fang, Kechi ^a   Zhao, Hansheng ^a,b   Sun, Changyue ^a   Lam, Carolyn M C ^c   Chang, Suhua ^a,d   Zhang, Kunlin ^a   Panda, Gurudutta ^c   Godinho, Miguel ^c,e   Martins dos Santos, Vítor A P ^c,f   Wang, Jing ^a  

^a INSTITUTE OF PSYCHOLOGY   (China)

^b CHINA AGRICULTURAL UNIVERSITY   (China)

^c HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^d UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^e Lifewizz Lda   (Portugal)

^f WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BURKHOLDERIA CENOCEPACIA;

ANTIINFECTIVE AGENT; FATTY ACID; LIPOPOLYSACCHARIDE;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GENOME; BIOLOGICAL MODEL; BIOLOGY; BIOMASS; BURKHOLDERIA CENOCEPACIA; BURKHOLDERIA INFECTION; CATALYSIS; GENETICS; GENOME; HUMAN; METABOLISM; METHODOLOGY; MICROBIOLOGY; PHENOTYPE; STATISTICAL MODEL; SYSTEMS BIOLOGY;

ANTI-BACTERIAL AGENTS; BIOMASS; BURKHOLDERIA CENOCEPACIA; BURKHOLDERIA INFECTIONS; CATALYSIS; COMPUTATIONAL BIOLOGY; DRUG RESISTANCE, BACTERIAL; FATTY ACIDS; GENOME; GENOME, BACTERIAL; HUMANS; LIPOPOLYSACCHARIDES; MODELS, BIOLOGICAL; MODELS, STATISTICAL; PHENOTYPE; SYSTEMS BIOLOGY;

EID: 80053352451     PISSN: None     EISSN: 17520509     Source Type: Journal    
DOI: 10.1186/1752-0509-5-83     Document Type: Article

References (96)

1. Mahenthiralingam E, Baldwin A, Dowson CG. Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol 2008, 104:1539-1551. 10.1111/j.1365-2672.2007.03706.x, 18217926.
2. Vanlaere E, Lipuma JJ, Baldwin A, Henry D, De Brandt E, Mahenthiralingam E, Speert D, Dowson C, Vandamme P. Burkholderia latens sp. nov., Burkholderia diffusa sp. nov., Burkholderia arboris sp. nov., Burkholderia seminalis sp. nov. and Burkholderia metallica sp. nov., novel species within the Burkholderia cepacia complex. Int J Syst Evol Microbiol 2008, 58:1580-1590. 10.1099/ijs.0.65634-0, 18599699.
3. Vanlaere E, Baldwin A, Gevers D, Henry D, De Brandt E, LiPuma JJ, Mahenthiralingam E, Speert DP, Dowson C, Vandamme P. Taxon K, a complex within the Burkholderia cepacia complex, comprises at least two novel species, Burkholderia contaminans sp. nov. and Burkholderia lata sp. nov. Int J Syst Evol Microbiol 2009, 59:102-111. 10.1099/ijs.0.001123-0, 19126732.
4. Parke JL, Gurian-Sherman D. Diversity of the Burkholderia cepacia complex and implications for risk assessment of biological control strains. Annu Rev Phytopathol 2001, 39:225-258. 10.1146/annurev.phyto.39.1.225, 11701865.
5. Mahenthiralingam E, Baldwin A, Vandamme P. Burkholderia cepacia complex infection in patients with cystic fibrosis. J Med Microbiol 2002, 51:533-538.
6. Mahenthiralingam E, Urban TA, Goldberg JB. The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 2005, 3:144-156. 10.1038/nrmicro1085, 15643431.
7. Mann T, Ben-David D, Zlotkin A, Shachar D, Keller N, Toren A, Nagler A, Smollan G, Barzilai A, Rahav G. An outbreak of Burkholderia cenocepacia bacteremia in immunocompromised oncology patients. Infection 2010,
8. Govan JR, Brown PH, Maddison J, Doherty CJ, Nelson JW, Dodd M, Greening AP, Webb AK. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 1993, 342:15-19. 10.1016/0140-6736(93)91881-L, 7686239.
9. Martin DW, Mohr CD. Invasion and intracellular survival of Burkholderia cepacia. Infect Immun 2000, 68:24-29. 10.1128/IAI.68.1.24-29.2000, 97097, 10603364.
10. Vandamme P, Holmes B, Coenye T, Goris J, Mahenthiralingam E, LiPuma JJ, Govan JR. Burkholderia cenocepacia sp. nov.--a new twist to an old story. Res Microbiol 2003, 154:91-96. 10.1016/S0923-2508(03)00026-3, 12648723.
11. Drevinek P, Holden MT, Ge Z, Jones AM, Ketchell I, Gill RT, Mahenthiralingam E. Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum. BMC Infect Dis 2008, 8:121. 10.1186/1471-2334-8-121, 2559838, 18801206.
12. Dubarry N, Du W, Lane D, Pasta F. Improved electrotransformation and decreased antibiotic resistance of the cystic fibrosis pathogen Burkholderia cenocepacia strain J2315. Appl Environ Microbiol 2010, 76:1095-1102. 10.1128/AEM.02123-09, 2820974, 20023084.
13. Holden MT, Seth-Smith HM, Crossman LC, Sebaihia M, Bentley SD, Cerdeno-Tarraga AM, Thomson NR, Bason N, Quail MA, Sharp S, et al. The genome of Burkholderia cenocepacia J2315, an epidemic pathogen of cystic fibrosis patients. J Bacteriol 2009, 191:261-277. 10.1128/JB.01230-08, 2612433, 18931103.
14. Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 1998, 42:2206-2214. 105778, 9736536.
15. Loutet SA, Flannagan RS, Kooi C, Sokol PA, Valvano MA. A complete lipopolysaccharide inner core oligosaccharide is required for resistance of Burkholderia cenocepacia to antimicrobial peptides and bacterial survival in vivo. J Bacteriol 2006, 188:2073-2080. 10.1128/JB.188.6.2073-2080.2006, 1428139, 16513737.
16. Miller JM, Rhoden DL. Preliminary evaluation of Biolog, a carbon source utilization method for bacterial identification. J Clin Microbiol 1991, 29:1143-1147. 269959, 1864931.
17. Reed JL, Vo TD, Schilling CH, Palsson BO. An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biology 2003, 4:R45. 10.1186/gb-2003-4-7-r45, 193632, 12844361.
18. Lee DS, Burd H, Liu J, Almaas E, Wiest O, Barabasi AL, Oltvai ZN, Kapatral V. Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets. J Bacteriol 2009, 191:4015-4024. 10.1128/JB.01743-08, 2698402, 19376871.
19. Becker SA, Palsson BO. Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. BMC Microbiol 2005, 5:8. 10.1186/1471-2180-5-8, 1079855, 15752426.
20. Heinemann M, Kummel A, Ruinatscha R, Panke S. In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network. Biotechnol Bioeng 2005, 92:850-864. 10.1002/bit.20663, 16155945.
21. Kim HU, Kim TY, Lee SY. Genome-scale metabolic network analysis and drug targeting of multi-drug resistant pathogen Acinetobacter baumannii AYE. Mol Biosyst 2010, 6:339-348. 10.1039/b916446d, 20094653.
22. Jamshidi N, Palsson BO. Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets. BMC Syst Biol 2007, 1:26. 10.1186/1752-0509-1-26, 1925256, 17555602.
23. Raghunathan A, Reed J, Shin S, Palsson B, Daefler S. Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction. BMC Syst Biol 2009, 3:38. 10.1186/1752-0509-3-38, 2678070, 19356237.
24. Oberhardt MA, Puchalka J, Fryer KE, Martins dos Santos VA, Papin JA. Genome-scale metabolic network analysis of the opportunistic pathogen Pseudomonas aeruginosa PAO1. J Bacteriol 2008, 190:2790-2803. 10.1128/JB.01583-07, 2293256, 18192387.
25. Eberl L. Quorum sensing in the genus Burkholderia. Int J Med Microbiol 2006, 296:103-110.
26. Eberl L. From a local dialect to a common language. Chem Biol 2006, 13:803-804. 10.1016/j.chembiol.2006.07.007, 16931327.
27. Sokol PA, Malott RJ, Riedel K, Eberl L. Communication systems in the genus Burkholderia: global regulators and targets for novel antipathogenic drugs. Future Microbiol 2007, 2:555-563. 10.2217/17460913.2.5.555, 17927476.
28. Boon C, Deng Y, Wang LH, He Y, Xu JL, Fan Y, Pan SQ, Zhang LH. A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida albicans morphological transition. ISME J 2008, 2:27-36. 10.1038/ismej.2007.76, 18049456.
29. Deng Y, Boon C, Eberl L, Zhang LH. Differential modulation of Burkholderia cenocepacia virulence and energy metabolism by the quorum-sensing signal BDSF and its synthase. J Bacteriol 2009, 191:7270-7278. 10.1128/JB.00681-09, 2786553, 19801414.
30. Ryan RP, McCarthy Y, Watt SA, Niehaus K, Dow JM. Intraspecies signaling involving the diffusible signal factor BDSF (cis-2-dodecenoic acid) influences virulence in Burkholderia cenocepacia. J Bacteriol 2009, 191:5013-5019. 10.1128/JB.00473-09, 2715730, 19482924.
31. Sokol PA, Darling P, Woods DE, Mahenthiralingam E, Kooi C. Role of ornibactin biosynthesis in the virulence of Burkholderia cepacia: characterization of pvdA, the gene encoding L-ornithine N(5)-oxygenase. Infect Immun 1999, 67:4443-4455. 96763, 10456885.
32. Farmer KL, Thomas MS. Isolation and characterization of Burkholderia cenocepacia mutants deficient in pyochelin production: pyochelin biosynthesis is sensitive to sulfur availability. J Bacteriol 2004, 186:270-277. 10.1128/JB.186.2.270-277.2004, 305768, 14702294.
33. Visser MB, Majumdar S, Hani E, Sokol PA. Importance of the ornibactin and pyochelin siderophore transport systems in Burkholderia cenocepacia lung infections. Infect Immun 2004, 72:2850-2857. 10.1128/IAI.72.5.2850-2857.2004, 387874, 15102796.
34. Sajjan US, Sun L, Goldstein R, Forstner JF. Cable (cbl) type II pili of cystic fibrosis-associated Burkholderia (Pseudomonas) cepacia: nucleotide sequence of the cblA major subunit pilin gene and novel morphology of the assembled appendage fibers. J Bacteriol 1995, 177:1030-1038. 176699, 7532166.
35. Sajjan U, Ackerley C, Forstner J. Interaction of cblA/adhesin-positive Burkholderia cepacia with squamous epithelium. Cell Microbiol 2002, 4:73-86. 10.1046/j.1462-5822.2002.00171.x, 11896764.
36. Sajjan U, Liu L, Lu A, Spilker T, Forstner J, LiPuma JJ. Lack of cable pili expression by cblA-containing Burkholderia cepacia complex. Microbiology 2002, 148:3477-3484.
37. Tomich M, Herfst CA, Golden JW, Mohr CD. Role of flagella in host cell invasion by Burkholderia cepacia. Infect Immun 2002, 70:1799-1806. 10.1128/IAI.70.4.1799-1806.2002, 127839, 11895941.
38. Urban TA, Griffith A, Torok AM, Smolkin ME, Burns JL, Goldberg JB. Contribution of Burkholderia cenocepacia flagella to infectivity and inflammation. Infect Immun 2004, 72:5126-5134. 10.1128/IAI.72.9.5126-5134.2004, 517433, 15322006.
39. Hutchison ML, Poxton IR, Govan JR. Burkholderia cepacia produces a hemolysin that is capable of inducing apoptosis and degranulation of mammalian phagocytes. Infect Immun 1998, 66:2033-2039. 108160, 9573086.
40. Kooi C, Corbett CR, Sokol PA. Functional analysis of the Burkholderia cenocepacia ZmpA metalloprotease. J Bacteriol 2005, 187:4421-4429. 10.1128/JB.187.13.4421-4429.2005, 1151788, 15968051.
41. Kooi C, Subsin B, Chen R, Pohorelic B, Sokol PA. Burkholderia cenocepacia ZmpB is a broad-specificity zinc metalloprotease involved in virulence. Infect Immun 2006, 74:4083-4093. 10.1128/IAI.00297-06, 1489746, 16790782.
42. Kooi C, Sokol PA. Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides. Microbiology 2009, 155:2818-2825. 10.1099/mic.0.028969-0, 19542010.
43. Korbsrisate S, Tomaras AP, Damnin S, Ckumdee J, Srinon V, Lengwehasatit I, Vasil ML, Suparak S. Characterization of two distinct phospholipase C enzymes from Burkholderia pseudomallei. Microbiology 2007, 153:1907-1915. 10.1099/mic.0.2006/003004-0, 17526847.
44. Tomich M, Griffith A, Herfst CA, Burns JL, Mohr CD. Attenuated virulence of a Burkholderia cepacia type III secretion mutant in a murine model of infection. Infect Immun 2003, 71:1405-1415. 10.1128/IAI.71.3.1405-1415.2003, 148827, 12595458.
45. Engledow AS, Medrano EG, Mahenthiralingam E, LiPuma JJ, Gonzalez CF. Involvement of a plasmid-encoded type IV secretion system in the plant tissue watersoaking phenotype of Burkholderia cenocepacia. J Bacteriol 2004, 186:6015-6024. 10.1128/JB.186.18.6015-6024.2004, 515160, 15342570.
46. Markey KM, Glendinning KJ, Morgan JA, Hart CA, Winstanley C. Caenorhabditis elegans killing assay as an infection model to study the role of type III secretion in Burkholderia cenocepacia. J Med Microbiol 2006, 55:967-969. 10.1099/jmm.0.46618-0, 16772429.
47. Ortega X, Hunt TA, Loutet S, Vinion-Dubiel AD, Datta A, Choudhury B, Goldberg JB, Carlson R, Valvano MA. Reconstitution of O-specific lipopolysaccharide expression in Burkholderia cenocepacia strain J2315, which is associated with transmissible infections in patients with cystic fibrosis. J Bacteriol 2005, 187:1324-1333. 10.1128/JB.187.4.1324-1333.2005, 545620, 15687196.
48. Hunt TA, Kooi C, Sokol PA, Valvano MA. Identification of Burkholderia cenocepacia genes required for bacterial survival in vivo. Infect Immun 2004, 72:4010-4022. 10.1128/IAI.72.7.4010-4022.2004, 427415, 15213146.
49. De Soyza A, Silipo A, Lanzetta R, Govan JR, Molinaro A. Chemical and biological features of Burkholderia cepacia complex lipopolysaccharides. Innate Immun 2008, 14:127-144. 10.1177/1753425908093984, 18562572.
50. Parsons YN, Banasko R, Detsika MG, Duangsonk K, Rainbow L, Hart CA, Winstanley C. Suppression-subtractive hybridisation reveals variations in gene distribution amongst the Burkholderia cepacia complex, including the presence in some strains of a genomic island containing putative polysaccharide production genes. Arch Microbiol 2003, 179:214-223.
51. Silipo A, Molinaro A, Ierano T, De Soyza A, Sturiale L, Garozzo D, Aldridge C, Corris PA, Khan CM, Lanzetta R, Parrilli M. The complete structure and pro-inflammatory activity of the lipooligosaccharide of the highly epidemic and virulent gram-negative bacterium Burkholderia cenocepacia ET-12 (strain J2315). Chemistry 2007, 13:3501-3511. 10.1002/chem.200601406, 17219455.
52. Ortega X, Silipo A, Saldias MS, Bates CC, Molinaro A, Valvano MA. Biosynthesis and structure of the Burkholderia cenocepacia K56-2 lipopolysaccharide core oligosaccharide: truncation of the core oligosaccharide leads to increased binding and sensitivity to polymyxin B. J Biol Chem 2009, 284:21738-21751. 10.1074/jbc.M109.008532, 2755896, 19525227.
53. Vinion-Dubiel AD, Goldberg JB. Lipopolysaccharide of Burkholderia cepacia complex. J Endotoxin Res 2003, 9:201-213.
54. Ortega XP, Cardona ST, Brown AR, Loutet SA, Flannagan RS, Campopiano DJ, Govan JR, Valvano MA. A putative gene cluster for aminoarabinose biosynthesis is essential for Burkholderia cenocepacia viability. J Bacteriol 2007, 189:3639-3644. 10.1128/JB.00153-07, 1855895, 17337576.
55. Chung HS, Raetz CRH. Identification and characterization of a 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) oxidase; KdoO. The FASEB Journal 2010,
56. Kenna DT, Barcus VA, Langley RJ, Vandamme P, Govan JR. Lack of correlation between O-serotype, bacteriophage susceptibility and genomovar status in the Burkholderia cepacia complex. FEMS Immunol Med Microbiol 2003, 35:87-92. 10.1016/S0928-8244(02)00442-X, 12628542.
57. Malott RJ, Baldwin A, Mahenthiralingam E, Sokol PA. Characterization of the cciIR quorum-sensing system in Burkholderia cenocepacia. Infect Immun 2005, 73:4982-4992. 10.1128/IAI.73.8.4982-4992.2005, 1201253, 16041013.
58. Williams P, Winzer K, Chan WC, Camara M. Look who's talking: communication and quorum sensing in the bacterial world. Philos Trans R Soc Lond B Biol Sci 2007, 362:1119-1134. 10.1098/rstb.2007.2039, 2435577, 17360280.
59. Baldwin A, Sokol PA, Parkhill J, Mahenthiralingam E. The Burkholderia cepacia epidemic strain marker is part of a novel genomic island encoding both virulence and metabolism-associated genes in Burkholderia cenocepacia. Infect Immun 2004, 72:1537-1547. 10.1128/IAI.72.3.1537-1547.2004, 356040, 14977960.
60. Diggle SP, Matthijs S, Wright VJ, Fletcher MP, Chhabra SR, Lamont IL, Kong X, Hider RC, Cornelis P, Camara M, Williams P. The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment. Chem Biol 2007, 14:87-96. 10.1016/j.chembiol.2006.11.014, 17254955.
61. Dubeau D, Deziel E, Woods DE, Lepine F. Burkholderia thailandensis harbors two identical rhl gene clusters responsible for the biosynthesis of rhamnolipids. BMC Microbiol 2009, 9:263. 10.1186/1471-2180-9-263, 2804600, 20017946.
62. Coenye T, Vandamme P, Govan JR, LiPuma JJ. Taxonomy and identification of the Burkholderia cepacia complex. J Clin Microbiol 2001, 39:3427-3436. 10.1128/JCM.39.10.3427-3436.2001, 88367, 11574551.
63. Wilkinson S, Pitt T. Burkholderia (Pseudomonas) cepacia: Surface chemistry and typing methods. REV MED MICROBIOL 1995, 6:1-9.
64. Taylor CJ, Anderson AJ, Wilkinson SG. Phenotypic variation of lipid composition in Burkholderia cepacia: a response to increased growth temperature is a greater content of 2-hydroxy acids in phosphatidylethanolamine and ornithine amide lipid. Microbiology 1998, 144(Pt 7):1737-1745.
65. Gao JL, Weissenmayer B, Taylor AM, Thomas-Oates J, Lopez-Lara IM, Geiger O. Identification of a gene required for the formation of lyso-ornithine lipid, an intermediate in the biosynthesis of ornithine-containing lipids. Mol Microbiol 2004, 53:1757-1770. 10.1111/j.1365-2958.2004.04240.x, 15341653.
66. Harayama S, Bollinger J, Iino T, Hazelbauer GL. Characterization of the mgl operon of Escherichia coli by transposon mutagenesis and molecular cloning. J Bacteriol 1983, 153:408-415. 217387, 6294056.
67. Stamm LV, Young NR, Frye JG, Hardham JM. Identification and sequences of the Treponema pallidum mglA and mglC genes. DNA Seq 1996, 6:293-298.
68. Koonin EV. Comparative genomics, minimal gene-sets and the last universal common ancestor. Nat Rev Microbiol 2003, 1:127-136. 10.1038/nrmicro751, 15035042.
69. Jacobs MA, Alwood A, Thaipisuttikul I, Spencer D, Haugen E, Ernst S, Will O, Kaul R, Raymond C, Levy R, et al. Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 2003, 100:14339-14344. 10.1073/pnas.2036282100, 283593, 14617778.
70. Liberati NT, Urbach JM, Miyata S, Lee DG, Drenkard E, Wu G, Villanueva J, Wei T, Ausubel FM. An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci USA 2006, 103:2833-2838. 10.1073/pnas.0511100103, 1413827, 16477005.
71. Yabuuchi E, Kosako Y, Oyaizu H, Yano I, Hotta H, Hashimoto Y, Ezaki T, Arakawa M. Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. Microbiol Immunol 1992, 36:1251-1275.
72. Cronan JE, Waldrop GL. Multi-subunit acetyl-CoA carboxylases. Prog Lipid Res 2002, 41:407-435. 10.1016/S0163-7827(02)00007-3, 12121720.
73. Li SJ, Cronan JE. Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzes the first committed step of lipid biosynthesis. J Bacteriol 1993, 175:332-340. 196146, 7678242.
74. Abdel-Hamid AM, Cronan JE. Coordinate expression of the acetyl coenzyme A carboxylase genes, accB and accC, is necessary for normal regulation of biotin synthesis in Escherichia coli. J Bacteriol 2007, 189:369-376. 10.1128/JB.01373-06, 1797400, 17056747.
75. Yoder-Himes DR, Konstantinidis KT, Tiedje JM. Identification of potential therapeutic targets for Burkholderia cenocepacia by comparative transcriptomics. PLoS One 2010, 5:e8724. 10.1371/journal.pone.0008724, 2806911, 20090946.
76. Perumal D, Samal A, Sakharkar KR, Sakharkar MK. Targeting multiple targets in Pseudomonas aeruginosa PAO1 using flux balance analysis of a reconstructed genome-scale metabolic network. J Drug Target 2010,
77. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M. DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res 2008, 36:D901-906. 2238889, 18048412.
78. Zhang L, Parente J, Harris SM, Woods DE, Hancock RE, Falla TJ. Antimicrobial peptide therapeutics for cystic fibrosis. Antimicrob Agents Chemother 2005, 49:2921-2927. 10.1128/AAC.49.7.2921-2927.2005, 1168697, 15980369.
79. Mookherjee N, Hancock RE. Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci 2007, 64:922-933. 10.1007/s00018-007-6475-6, 17310278.
80. Loutet SA, Bartholdson SJ, Govan JR, Campopiano DJ, Valvano MA. Contributions of two UDP-glucose dehydrogenases to viability and polymyxin B resistance of Burkholderia cenocepacia. Microbiology 2009, 155:2029-2039. 10.1099/mic.0.027607-0, 19383677.
81. Edwards JS, Covert M, Palsson BO. Metabolic modelling of microbes:the flux-balance approach. Environmental Microbiology 2002, 4:133-140. 10.1046/j.1462-2920.2002.00282.x, 12000313.
82. Diez MS, Lam CM, Leprince A, dos Santos VA. (Re-)construction, characterization and modeling of systems for synthetic biology. Biotechnol J 2009, 4:1382-1391. 10.1002/biot.200900173, 19830713.
83. Hertz-Fowler C, Peacock CS, Wood V, Aslett M, Kerhornou A, Mooney P, Tivey A, Berriman M, Hall N, Rutherford K, et al. GeneDB: a resource for prokaryotic and eukaryotic organisms. Nucleic Acids Res 2004, 32:D339-343. 10.1093/nar/gkh007, 308742, 14681429.
84. Schomburg I, Chang A, Ebeling C, Gremse M, Heldt C, Huhn G, Schomburg D. BRENDA, the enzyme database: updates and major new developments. Nucleic Acids Res 2004, 32:D431-433. 10.1093/nar/gkh081, 308815, 14681450.
85. Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 2006, 34:D354-357. 10.1093/nar/gkj102, 1347464, 16381885.
86. Ren Q, Chen K, Paulsen IT. TransportDB: a comprehensive database resource for cytoplasmic membrane transport systems and outer membrane channels. Nucleic Acids Res 2007, 35:D274-279. 10.1093/nar/gkl925, 1747178, 17135193.
87. The universal protein resource (UniProt). Nucleic Acids Res 2008, 36:D190-195. 10.1093/nar/gkn141, 2238893, 18045787.
88. Saier MH, Tran CV, Barabote RD. TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res 2006, 34:D181-186. 10.1093/nar/gkj001, 1334385, 16381841.
89. Orth JD, Palsson BO. Systematizing the generation of missing metabolic knowledge. Biotechnol Bioeng 2010, 107:403-412. 10.1002/bit.22844, 20589842.
90. Reed JL, Patel TR, Chen KH, Joyce AR, Applebee MK, Herring CD, Bui OT, Knight EM, Fong SS, Palsson BO. Systems approach to refining genome annotation. Proc Natl Acad Sci USA 2006, 103:17480-17484. 10.1073/pnas.0603364103, 1859954, 17088549.
91. Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson B. A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Molecular Systems Biology 2007, 3.
92. Krejci E, Kroppenstedt RM. Defferentiation of Species Combined into the Burkholderia cepacia Complex and Related Taxa on the Basis of Their Fatty Acid Patterns. Journal of Clinical Microbiology 2006, 44.
93. Sousa SA, Ramos CG, Almeida F, Meirinhos-Soares L, Wopperer J, Schwager S, Eberl L, Leitao JH. Burkholderia cenocepacia J2315 acyl carrier protein: a potential target for antimicrobials' development?. Microb Pathog 2008, 45:331-336. 10.1016/j.micpath.2008.08.002, 18771721.
94. Miller JH. Experiments in molecular genetics 1972, Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory.
95. Palmer KL, Aye LM, Whiteley M. Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J Bacteriol 2007, 189:8079-8087. 10.1128/JB.01138-07, 2168676, 17873029.
96. Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S. Experimental and computational assessment of conditionally essential genes in Escherichia coli. J Bacteriol 2006, 188:8259-8271. 10.1128/JB.00740-06, 1698209, 17012394.