Expression of urease by Haemophilus influenzaeduring human respiratory tract infection and role in survival in an acid environment
Tóm tắt
Nontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Prior studies have shown that H. influenzae expresses abundant urease during growth in the middle ear of the chinchilla and in pooled human sputum, suggesting that expression of urease is important for colonization and infection in the hostile environments of the middle ear and in the airways in adults. Virtually nothing else is known about the urease of H. influenzae, which was characterized in the present study. Analysis by reverse transcriptase PCR revealed that the ure gene cluster is expressed as a single transcript. Knockout mutants of a urease structural gene (ureC) and of the entire ure operon demonstrated no detectable urease activity indicating that this operon is the only one encoding an active urease. The ure operon is present in all strains tested, including clinical isolates from otitis media and COPD. Urease activity decreased as nitrogen availability increased. To test the hypothesis that urease is expressed during human infection, purified recombinant urease C was used in ELISA with pre acquisition and post infection serum from adults with COPD who experienced infections caused by H. influenzae. A total of 28% of patients developed new antibodies following infection indicating that H. influenzae expresses urease during airway infection. Bacterial viability assays performed at varying pH indicate that urease mediates survival of H. influenzae in an acid environment. The H. influenzae genome contains a single urease operon that mediates urease expression and that is present in all clinical isolates tested. Nitrogen availability is a determinant of urease expression. H. influenzae expresses urease during human respiratory tract infection and urease is a target of the human antibody response. Expression of urease enhances viability in an acid environment. Taken together, these observations suggest that urease is important for survival and replication of H. influenzae in the human respiratory tract.
Tài liệu tham khảo
Murphy TF, Faden H, Bakaletz LO, Kyd JM, Forsgren A, Campos J, Virji M, Pelton SI: Nontypeable Haemophilus influenzae as a pathogen in children. Pediatr Infect Dis J. 2009, 28 (1): 43-48. 10.1097/INF.0b013e318184dba2.
Sethi S, Murphy TF: Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008, 359 (22): 2355-2365. 10.1056/NEJMra0800353.
Murphy TF: Respiratory infections caused by non-typeable Haemophilus influenzae. Curr Opin Infect Dis. 2003, 16 (2): 129-134. 10.1097/00001432-200304000-00009.
Zalacain R, Sobradillo V, Amilibia J, Barron J, Achotegui V, Pijoan JI, Llorente JL: Predisposing factors to bacterial colonization in chronic obstructive pulmonary disease. Eur Respir J. 1999, 13: 343-348. 10.1034/j.1399-3003.1999.13b21.x.
Soler N, Torres A, Ewig S, Gonzalez J, Celis R, El-Ebiary M, Hernandez C, Rodriguez-Roisin R: Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med. 1998, 157: 1498-1505.
Sethi S, Maloney J, Grove L, Wrona C, Berenson CS: Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006, 173 (9): 991-998. 10.1164/rccm.200509-1525OC.
Monso E, Ruiz J, Rosell A, Manterola J, Fiz J, Morera J, Ausina V: Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med. 1995, 152: 1316-1320.
Drost EM, Skwarski KM, Sauleda J, Soler N, Roca J, Agusti A, MacNee W: Oxidative stress and airway inflammation in severe exacerbations of COPD. Thorax. 2005, 60 (4): 293-300. 10.1136/thx.2004.027946.
Gerritsen WB, Asin J, Zanen P, van den Bosch JM, Haas FJ: Markers of inflammation and oxidative stress in exacerbated chronic obstructive pulmonary disease patients. Respir Med. 2005, 99 (1): 84-90. 10.1016/j.rmed.2004.04.017.
Dekhuijzen PN, Aben KK, Dekker I, Aarts LP, Wielders PL, van Herwaarden CL, Bast A: Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996, 154 (3 Pt 1): 813-816.
Barnes PJ: The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2009, 41 (6): 631-638. 10.1165/rcmb.2009-0220TR.
Barnes PJ: Chronic obstructive pulmonary disease. N Engl J Med. 2000, 343 (4): 269-280. 10.1056/NEJM200007273430407.
Qu J, Lesse AJ, Brauer AL, Cao J, Gill SR, Murphy TF: Proteomic expression profiling of Haemophilus influenzae grown in pooled human sputum from adults with chronic obstructive pulmonary disease reveal antioxidant and stress responses. BMC Microbiol. 2010, 10: 162-10.1186/1471-2180-10-162.
Mason KM, Munson RS, Bakaletz LO: Nontypeable Haemophilus influenzae gene expression induced in vivo in a chinchilla model of otitis media. Infect Immun. 2003, 71 (6): 3454-3462. 10.1128/IAI.71.6.3454-3462.2003.
Mobley HL, Island MD, Hausinger RP: Molecular biology of microbial ureases. Microbiol Rev. 1995, 59 (3): 451-480.
Mobley HLT: Urease. Helicobacter pylori: Physiology and Genetics. Edited by: Mobley HLT, Mendz GL, Hazell SL. 2001, Washington DC: ASM Press, 2011/02/04 edn
Molnar B, Galamb O, Sipos F, Leiszter K, Tulassay Z: Molecular pathogenesis of Helicobacter pylori infection: the role of bacterial virulence factors. Dig Dis. 2010, 28 (4-5): 604-608. 10.1159/000320060.
Schoep TD, Fulurija A, Good F, Lu W, Himbeck RP, Schwan C, Choi SS, Berg DE, Mittl PR, Benghezal M, Marshall BJ: Surface properties of Helicobacter pylori urease complex are essential for persistence. PLoS One. 2010, 5 (11): e15042.-
Stingl K, Altendorf K, Bakker EP: Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis?. Trends Microbiol. 2002, 10 (2): 70-74. 10.1016/S0966-842X(01)02287-9.
Stingl K, Uhlemann EM, Schmid R, Altendorf K, Bakker EP: Energetics of Helicobacter pylori and its implications for the mechanism of urease-dependent acid tolerance at pH 1. J Bacteriol. 2002, 184 (11): 3053-3060. 10.1128/JB.184.11.3053-3060.2002.
Coker C, Poore CA, Li X, Mobley HL: Pathogenesis of Proteus mirabilis urinary tract infection. Microbes Infect. 2000, 2 (12): 1497-1505. 10.1016/S1286-4579(00)01304-6.
Dattelbaum JD, Lockatell CV, Johnson DE, Mobley HL: UreR, the transcriptional activator of the Proteus mirabilis urease gene cluster, is required for urease activity and virulence in experimental urinary tract infections. Infect Immun. 2003, 71 (2): 1026-1030. 10.1128/IAI.71.2.1026-1030.2003.
Island MD, Mobley HL: Proteus mirabilis urease: operon fusion and linker insertion analysis of ure gene organization, regulation, and function. J Bacteriol. 1995, 177 (19): 5653-5660.
Burne RA, Chen YY: Bacterial ureases in infectious diseases. Microbes Infect. 2000, 2 (5): 533-542. 10.1016/S1286-4579(00)00312-9.
Sangari FJ, Seoane A, Rodriguez MC, Aguero J, Garcia Lobo JM: Characterization of the urease operon of Brucella abortus and assessment of its role in virulence of the bacterium. Infect Immun. 2007, 75 (2): 774-780. 10.1128/IAI.01244-06.
Maroncle N, Rich C, Forestier C: The role of Klebsiella pneumoniae urease in intestinal colonization and resistance to gastrointestinal stress. Res Microbiol. 2006, 157 (2): 184-193. 10.1016/j.resmic.2005.06.006.
Olivera-Severo D, Wassermann GE, Carlini CR: Ureases display biological effects independent of enzymatic activity: is there a connection to diseases caused by urease-producing bacteria?. Braz J Med Biol Res. 2006, 39 (7): 851-861. 10.1590/S0100-879X2006000700002.
Williams CL, Preston T, Hossack M, Slater C, McColl KE: Helicobacter pylori utilises urea for amino acid synthesis. FEMS Immunol Med Microbiol. 1996, 13 (1): 87-94. 10.1111/j.1574-695X.1996.tb00220.x.
Harris PR, Ernst PB, Kawabata S, Kiyono H, Graham MF, Smith PD: Recombinant Helicobacter pylori urease activates primary mucosal macrophages. J Infect Dis. 1998, 178 (5): 1516-1520. 10.1086/314426.
Zhang JY, Liu T, Guo H, Liu XF, Zhuang Y, Yu S, Chen L, Wu C, Zhao Z, Tang B, Luo P, Mao XH, Guo G, Shi Y, Zou QM: Induction of a Th17 cell response by Helicobacter pylori urease subunit B. Immunobiology. 2010
Tanahashi T, Kita M, Kodama T, Yamaoka Y, Sawai N, Ohno T, Mitsufuji S, Wei YP, Kashima K, Imanishi J: Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells. Infect Immun. 2000, 68 (2): 664-671. 10.1128/IAI.68.2.664-671.2000.
Harris PR, Mobley HL, Perez-Perez GI, Blaser MJ, Smith PD: Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production. Gastroenterology. 1996, 111 (2): 419-425. 10.1053/gast.1996.v111.pm8690207.
Wroblewski LE, Shen L, Ogden S, Romero-Gallo J, Lapierre LA, Israel DA, Turner JR, Peek RM: Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation. Gastroenterology. 2009, 136 (1): 236-246. 10.1053/j.gastro.2008.10.011.
Fan X, Gunasena H, Cheng Z, Espejo R, Crowe SE, Ernst PB, Reyes VE: Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis. J Immunol. 2000, 165 (4): 1918-1924.
Schwartz JT, Allen LA: Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J Leukoc Biol. 2006, 79 (6): 1214-1225. 10.1189/jlb.0106030.
Makristathis A, Rokita E, Labigne A, Willinger B, Rotter ML, Hirschl AM: Highly significant role of Helicobacter pylori urease in phagocytosis and production of oxygen metabolites by human granulocytes. J Infect Dis. 1998, 177 (3): 803-806. 10.1086/517814.
Kuwahara H, Miyamoto Y, Akaike T, Kubota T, Sawa T, Okamoto S, Maeda H: Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production. Infect Immun. 2000, 68 (8): 4378-4383. 10.1128/IAI.68.8.4378-4383.2000.
Rokita E, Makristathis A, Presterl E, Rotter ML, Hirschl AM: Helicobacter pylori urease significantly reduces opsonization by human complement. J Infect Dis. 1998, 178 (5): 1521-1525. 10.1086/314459.
Bakaletz LO, Baker BD, Jurcisek JA, Harrison A, Novotny LA, Bookwalter JE, Mungur R, Munson RS: Demonstration of Type IV pilus expression and a twitching phenotype by Haemophilus influenzae. Infect Immun. 2005, 73 (3): 1635-1643. 10.1128/IAI.73.3.1635-1643.2005.
Erwin AL, Nelson KL, Mhlanga-Mutangadura T, Bonthuis PJ, Geelhood JL, Morlin G, Unrath WC, Campos J, Crook DW, Farley MM, Henderson FW, Jacobs RF, Muhlemann K, Satola SW, van Alphen L, Golomb M, Smith AL: Characterization of genetic and phenotypic diversity of invasive nontypeable Haemophilus influenzae. Infect Immun. 2005, 73 (9): 5853-5863. 10.1128/IAI.73.9.5853-5863.2005.
Sethi S, Wrona C, Grant BJ, Murphy TF: Strain-specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004, 169: 448-453.
Adlowitz DG, Kirkham C, Sethi S, Murphy TF: Human serum and mucosal antibody responses to outer membrane protein G1b of Moraxella catarrhalis in chronic obstructive pulmonary disease. FEMS Immunol Med Microbiol. 2006, 46 (1): 139-146. 10.1111/j.1574-695X.2005.00020.x.
Adlowitz DG, Sethi S, Cullen P, Adler B, Murphy TF: Human antibody response to outer membrane protein G1a, a lipoprotein of Moraxella catarrhalis. Infect Immun. 2005, 73 (10): 6601-6607. 10.1128/IAI.73.10.6601-6607.2005.
LaFontaine ER, Snipes LE, Bullard B, Brauer AL, Sethi S, Murphy TF: Identification of domains of the Hag/MID surface protein recognized by systemic and mucosal antibodies in adults with chronic obstructive pulmonary disease following clearance of Moraxella catarrhalis. Clin Vaccine Immunol. 2009, 16 (5): 653-659. 10.1128/CVI.00460-08.
Bosse JT, MacInnes JI: Urease activity may contribute to the ability of Actinobacillus pleuropneumoniae to establish infection. Canadian J Vet Res. 2000, 64 (3): 145-150.
Kaulbach HC, White MV, Igarashi Y, Hahn BK, Kaliner MA: Estimation of nasal epithelial lining fluid using urea as a marker. Journal Allergy Clin Immunol. 1993, 92 (3): 457-465. 10.1016/0091-6749(93)90125-Y.
Murphy TF, Kirkham C, Sethi S, Lesse AJ: Expression of a peroxiredoxin-glutaredoxin by Haemophilus influenzae in biofilms and during human respiratory tract infection. FEMS Immunol Med Microbiol. 2005, 44 (1): 81-89. 10.1016/j.femsim.2004.12.008.
Ruckdeschel EA, Kirkham C, Lesse AJ, Hu Z, Murphy TF: Mining the Moraxella catarrhalis genome: identification of potential vaccine antigens expressed during human infection. Infect Immun. 2008, 76 (4): 1599-1607. 10.1128/IAI.01253-07.
Rudd PT, Cassell GH, Waites KB, Davis JK, Duffy LB: Ureaplasma urealyticum pneumonia: experimental production and demonstration of age-related susceptibility. Infect Immun. 1989, 57 (3): 918-925.
Monack DM, Falkow S: Cloning of Bordetella bronchiseptica urease genes and analysis of colonization by a urease-negative mutant strain in a guinea-pig model. Mol Microbiol. 1993, 10 (3): 545-553. 10.1111/j.1365-2958.1993.tb00926.x.
Ketterer MR, Shao JQ, Hornick DB, Buscher B, Bandi VK, Apicella MA: Infection of primary human bronchial epithelial cells by Haemophilus influenzae: macropinocytosis as a mechanism of airway epithelial cell entry. Infect Immun. 1999, 67: 4161-4170.
Forsgren J, Samuelson A, Ahlin A, Jonasson J, Rynnel-Dagoo B, Lindberg A: Haemophilus influenzae resides and multiplies intracellularly in human adenoid tissue as demonstrated by in situ hybridization and bacterial viability assay. Infect Immun. 1994, 62: 673-679.
Bandi V, Apicella MA, Mason E, Murphy TF, Siddiqi A, Atmar RL, Greenberg SB: Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis. Am J Respir Crit Care Med. 2001, 164 (11): 2114-2119.
Sethi S, Evans N, Grant BJB, Murphy TF: New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002, 347: 465-471. 10.1056/NEJMoa012561.
Murphy TF, Brauer AL, Sethi S, Kilian M, Cai X, Lesse AJ: Haemophilus haemolyticus: a human respiratory tract commensal to be distinguished from Haemophilus influenzae. J Infect Dis. 2007, 195 (1): 81-89. 10.1086/509824.
Menard R, Sansonetti PJ, Parsot C: Nonpolar mutagenesis of the ipa genes defines IpaB, IpaC, and IpaD as effectors of Shigella flexneri entry into epithelial cells. J Bacteriol. 1993, 175 (18): 5899-5906.
Herriott RM, Meyer EY, Vogt M, Modan M: Defined medium for growth of Haemophilus influenzae. J Bacteriol. 1970, 101: 513-516.
Poje G, Redfield RJ: Transformation of Haemophilus influenzae. Haemophilus influenzae protocols. Edited by: Herbert M, Wood D, Moxon E. 2003, Totowa, NJ: Humana Press, 57-70.
Murphy TF, Kirkham C, Lesse AJ: Construction of a mutant and characterization of the role of the vaccine antigen P6 in outer membrane integrity of nontypeable Haemophilus influenzae. Infect Immun. 2006, 74 (9): 5169-5176. 10.1128/IAI.00692-06.
Senior BW, Bradford NC, Simpson DS: The ureases of Proteus strains in relation to virulence for the urinary tract. J Med Microbiol. 1980, 13 (4): 507-512. 10.1099/00222615-13-4-507.
American Thoracic Society: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995, 152 (5 Pt 2): S77-S121.
Sethi S, Muscarella K, Evans N, Klingman KL, Grant BJB, Murphy TF: Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Chest. 2000, 118: 1557-1565. 10.1378/chest.118.6.1557.
Murphy TF, Kirkham C, Liu DF, Sethi S: Human immune response to outer membrane protein CD of Moraxella catarrhalis in adults with chronic obstructive pulmonary disease. Infect Immun. 2003, 71 (3): 1288-1294. 10.1128/IAI.71.3.1288-1294.2003.