期刊论文详细信息
BMC Microbiology
Gene expression profiling of Mycobacterium avium subsp. paratuberculosis in simulated multi-stress conditions and within THP-1 cells reveals a new kind of interactive intramacrophage behaviour
Valentina Rosu1  Stefania Zanetti2  Leonardo Antonio Sechi2  Andrea Cossu2 
[1] Experimental Zooprophylactic Institute of Sardinia, Department of Nuoro, Nuoro, Italy;Department of Biomedical Sciences, Division of Experimental and Clinical Microbiology, University of Sassari, Sassari, Italy
关键词: macrophage infection;    simulated intra-phagosomal multi-stress;    DNA-microarray;    functional genomics;    Mycobacterium avium subsp. paratuberculosis;   
Others  :  1221928
DOI  :  10.1186/1471-2180-12-87
 received in 2012-01-14, accepted in 2012-05-30,  发布年份 2012
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【 摘 要 】

Background

Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, it is necessary a thorough understanding of MAP's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic and therapeutic tools.

Results

In order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures.

Conclusions

These results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health.

【 授权许可】

   
2012 Cossu et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Harris NB, Barletta RG: Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine. Clin Microbiol Rev 2001, 14:489-512.
  • [2]Sohal JS, Singh SV, Tyagi P, Subhodh S, Singh PK, Singh AV, Narayanasamy K, Sheoran N, Singh Sandhu K: Immunology of mycobacterial infections: with special reference to Mycobacterium avium subspecies paratuberculosis. Immunobiology 2008, 213:585-598.
  • [3]Coussens PM: Mycobacterium paratuberculosis and the bovine immune system. Anim Health Res Rev 2001, 2:141-161.
  • [4]Beard RM, Henderson D, Daniels MJ, Pirie A, Buxton D, Greig A, Hutchings MR, McKendrick I, Rhind S, Stevenson K, Sharp JM: Evidence of paratuberculosis in fox (Vulpes vulpes) and stoat (Mustela erminea). Vet Rec 1999, 145:612-613.
  • [5]Chiodini RJ: Crohn's disease and the mycobacterioses: a review and comparison of two disease entities. Clin Microbiol Rev 1989, 2:90-117.
  • [6]Gerlach GF: Paratuberculosis: the pathogen and routes of infection. DTW. Dtsch Tierarztl Wochenschr 2002, 109:504-506.
  • [7]Bull TJ, McMinn EJ, Sidi-Boumedine K, Skull A, Durkin D, Neild P, Rhodes G, Pickup R, Hermon-Taylor J: Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn's disease. J Clin Microbiol 2003, 41:2915-2923.
  • [8]Sechi LA, Scanu AM, Molicotti P, Cannas S, Mura M, Dettori G, Fadda G, Zanetti S: Detection and Isolation of Mycobacterium avium subspecies paratuberculosis from intestinal mucosal biopsies of patients with and without Crohn's disease in Sardinia. Am J Gastroenterol 2005, 100:1529-1536.
  • [9]Cossu A, Rosu V, Paccagnini D, Cossu D, Pacifico A, Sechi LA: MAP3738c and MptD are specific tags of Mycobacterium avium subsp. paratuberculosis infection in type I diabetes mellitus. Clin Immunol 2011, 141:49-57.
  • [10]Whittington RJ, Marshall DJ, Nicholls PJ, Marsh IB, Reddacliff LA: Survival and dormancy of Mycobacterium avium subsp. paratuberculosis in the environment. Appl Environ Microbiol 2004, 70:2989-3004.
  • [11]Donaghy JA, Totton NL, Rowe MT: Persistence of Mycobacterium paratuberculosis during manufacture and ripening of cheddar cheese. Appl Environ Microbiol 2004, 70:4899-4905.
  • [12]de Lisle GW, Yates GF, Joyce MA, Cavaignac SM, Hynes TJ, Collins DM: Case report and DNA characterization of Mycobacterium avium isolates from multiple animals with lesions in a beef cattle herd. J Vet Diagn Invest 1998, 10:283-284.
  • [13]Kuehnel MP, Goethe R, Habermann A, Mueller E, Rohde M, Griffiths G, Valentin-Weigand P: Characterization of the intracellular survival of Mycobacterium avium ssp. paratuberculosis: phagosomal pH and fusogenicity in J774 macrophages compared with other mycobacteria. Cell Microbiol 2001, 3:551-566.
  • [14]Hestvik ALK, Hmama Z, Av-Gay Y: Mycobacterial manipulation of the host cell. FEMS Microbiol Rev 2005, 29:1041-1050.
  • [15]Alonso S, Pethe K, Russell DG, Purdy GE: Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc Natl Acad Sci USA 2007, 104:6031-6036.
  • [16]Bannantine JP, Stabel JR: Killing of Mycobacterium avium subspecies paratuberculosis within macrophages. BMC Microbiol 2002, 2:2. BioMed Central Full Text
  • [17]Murphy JT, Sommer S, Kabara EA, Verman N, Kuelbs MA, Saama P, Halgren R, Coussens PM: Gene expression profiling of monocyte-derived macrophages following infection with Mycobacterium avium subspecies avium and Mycobacterium avium subspecies paratuberculosis. Physiol Genomics 2006, 28:67-75.
  • [18]Verschoor CP, Pant SD, You Q, Kelton DF, Karrow NA: Gene expression profiling of PBMCs from Holstein and Jersey cows sub-clinically infected with Mycobacterium avium ssp. paratuberculosis. Vet Immunol Immunopathol 2010, 137:1-11.
  • [19]Boshoff HIM, Myers TG, Copp BR, McNeil MR, Wilson MA, Barry CE: The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem 2004, 279:40174-40184.
  • [20]Zhu X, Tu ZJ, Coussens PM, Kapur V, Janagama H, Naser S, Sreevatsan S: Transcriptional analysis of diverse strains Mycobacterium avium subspecies paratuberculosis in primary bovine monocyte derived macrophages. Microbes Infect 2008, 10:1274-1282.
  • [21]Janagama HK, Lamont EA, George S, Bannantine JP, Xu WW, Tu ZJ, Wells SJ, Schefers J, Sreevatsan S: Primary transcriptomes of Mycobacterium avium subsp. paratuberculosis reveal proprietary pathways in tissue and macrophages. BMC Genomics 2010, 11:561. BioMed Central Full Text
  • [22]Sechi LA, Rosu V, Pacifico A, Fadda G, Ahmed N, Zanetti S: Humoral immune responses of type 1 diabetes patients to Mycobacterium avium subsp. paratuberculosis lend support to the infectious trigger hypothesis. Clin Vaccine Immunol 2008, 15:320-326.
  • [23]Chiodini RJ, Van Kruiningen HJ, Merkal RS, Thayer WR, Coutu JA: Characteristics of an unclassified Mycobacterium species isolated from patients with Crohn's disease. J Clin Microbiol 1984, 20:966-971.
  • [24]Rohde KH, Abramovitch RB, Russell DG: Mycobacterium tuberculosis invasion of macrophages: linking bacterial gene expression to environmental cues. Cell Host Microbe 2007, 2:352-364.
  • [25]Butcher PD, Mangan JA, Monahan IM: Intracellular gene expression. Analysis of RNA from mycobacteria in macrophages using RT-PCR. Methods Mol Biol 1998, 101:285-306.
  • [26]Kanehisa M, Goto S: KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000, 28:27-30.
  • [27]Uchiyama I: MBGD: a platform for microbial comparative genomics based on the automated construction of orthologous groups. Nucleic Acids Res 2007, 35:D343-D346.
  • [28]Hunter S, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bork P, Das U, Daugherty L, Duquenne L, Finn RD, Gough J, Haft D, Hulo N, Kahn D, Kelly E, Laugraud A, Letunic I, Lonsdale D, Lopez R, Madera M, Maslen J, McAnulla C, McDowall J, Mistry J, Mitchell A, Mulder N, Natale D, Orengo C, Quinn AF, Selengut JD, Sigrist CJA, Thimma M, Thomas PD, Valentin F, Wilson D, Wu CH, Yeats C: InterPro: the integrative protein signature database. Nucleic Acids Res 2009, 37:D211-D215.
  • [29]Bacon J, James BW, Wernisch L, Williams A, Morley KA, Hatch GJ, Mangan JA, Hinds J, Stoker NG, Butcher PD, Marsh PD: The influence of reduced oxygen availability on pathogenicity and gene expression in Mycobacterium tuberculosis. Tuberculosis (Edinb) 2004, 84:205-217.
  • [30]Fischer R, von Strandmann RP, Hengstenberg W: Mannitol-specific phosphoenolpyruvate-dependent phosphotransferase system of Enterococcus faecalis: molecular cloning and nucleotide sequences of the enzyme IIIMtl gene and the mannitol-1-phosphate dehydrogenase gene, expression in Escherichia coli, and comparison of the gene products with similar enzymes. J Bacteriol 1991, 173:3709-3715.
  • [31]Sára M, Sleytr UB: S-Layer proteins. J Bacteriol 2000, 182:859-868.
  • [32]Kneidinger B, Marolda C, Graninger M, Zamyatina A, McArthur F, Kosma P, Valvano MA, Messner P: Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli. J Bacteriol 2002, 184:363-369.
  • [33]van Asselt EJ, Thunnissen AM, Dijkstra BW: High resolution crystal structures of the Escherichia coli lytic transglycosylase Slt70 and its complex with a peptidoglycan fragment. J Mol Biol 1999, 291:877-898.
  • [34]Begg KJ, Dewar SJ, Donachie WD: A new Escherichia coli cell division gene, ftsK. J Bacteriol 1995, 177:6211-6222.
  • [35]Pérez E, Samper S, Bordas Y, Guilhot C, Gicquel B, Martín C: An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol 2001, 41:179-187.
  • [36]Ito T, Uozumi N, Nakamura T, Takayama S, Matsuda N, Aiba H, Hemmi H, Yoshimura T: The implication of YggT of Escherichia coli in osmotic regulation. Biosci Biotechnol Biochem 2009, 73:2698-2704.
  • [37]Körner H, Sofia HJ, Zumft WG: Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. FEMS Microbiol Rev 2003, 27:559-592.
  • [38]Graham JE, Clark-Curtiss JE: Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Proc Natl Acad Sci USA 1999, 96:11554-11559.
  • [39]Domenech P, Honoré N, Heym B, Cole ST: Role of OxyS of Mycobacterium tuberculosis in oxidative stress: overexpression confers increased sensitivity to organic hydroperoxides. Microbes Infect 2001, 3:713-721.
  • [40]Delumeau O, Dutta S, Brigulla M, Kuhnke G, Hardwick SW, Völker U, Yudkin MD, Lewis RJ: Functional and structural characterization of RsbU, a stress signaling protein phosphatase 2 C. J Biol Chem 2004, 279:40927-40937.
  • [41]Manganelli R, Dubnau E, Tyagi S, Kramer FR, Smith I: Differential expression of 10 sigma factor genes in Mycobacterium tuberculosis. Mol Microbiol 1999, 31:715-724.
  • [42]Sechi LA, Felis GE, Ahmed N, Paccagnini D, Usai D, Ortu S, Molicotti P, Zanetti S: Genome and transcriptome scale portrait of sigma factors in Mycobacterium avium subsp. paratuberculosis. Infect Genet Evol 2007, 7:424-432.
  • [43]Lam THJ, Yuen KY, Ho PL, Wong KC, Leong WM, Law HKW, Weng XH, Zhang WH, Chen S, Yam WC: Differential fadE28 expression associated with phenotypic virulence of Mycobacterium tuberculosis. Microb Pathog 2008, 45:12-17.
  • [44]Kisker C, Hinrichs W, Tovar K, Hillen W, Saenger W: The complex formed between Tet repressor and tetracycline-Mg2+ reveals mechanism of antibiotic resistance. J Mol Biol 1995, 247:260-280.
  • [45]Rosen BP: The plasmid-encoded arsenical resistance pump: an anion-translocating ATPase. Res Microbiol 1990, 141:336-341.
  • [46]Sampson SL: Mycobacterial PE/PPE proteins at the host-pathogen interface. Clin Dev Immunol 2011, 2011:497203.
  • [47]Schué M, Maurin D, Dhouib R, Bakala N'Goma J-C, Delorme V, Lambeau G, Carrière F, Canaan S: Two cutinase-like proteins secreted by Mycobacterium tuberculosis show very different lipolytic activities reflecting their physiological function. FASEB J 2010, 24:1893-1903.
  • [48]Bera A, Biswas R, Herbert S, Götz F: The presence of peptidoglycan O-acetyltransferase in various staphylococcal species correlates with lysozyme resistance and pathogenicity. Infect Immun 2006, 74:4598-4604.
  • [49]Mol CD, Kuo CF, Thayer MM, Cunningham RP, Tainer JA: Structure and function of the multifunctional DNA-repair enzyme exonuclease III. Nature 1995, 374:381-386.
  • [50]Sugahara M, Mikawa T, Kumasaka T, Yamamoto M, Kato R, Fukuyama K, Inoue Y, Kuramitsu S: Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8. EMBO J 2000, 19:3857-3869.
  • [51]Sousa MC, McKay DB: Structure of the universal stress protein of Haemophilus influenzae. Structure 2001, 9:1135-1141.
  • [52]Mihara H, Esaki N: Bacterial cysteine desulfurases: their function and mechanisms. Appl Microbiol Biotechnol 2002, 60:12-23.
  • [53]Gebhard S, Ekanayaka N, Cook GM: The low-affinity phosphate transporter PitA is dispensable for in vitro growth of Mycobacterium smegmatis. BMC Microbiol 2009, 9:254. BioMed Central Full Text
  • [54]Payne SM: Detection, isolation, and characterization of siderophores. Meth Enzymol 1994, 235:329-344.
  • [55]Hu Y, Coates AR: Increased levels of sigJ mRNA in late stationary phase cultures of Mycobacterium tuberculosis detected by DNA array hybridisation. FEMS Microbiol Lett 2001, 202:59-65.
  • [56]Deb C, Lee C-M, Dubey VS, Daniel J, Abomoelak B, Sirakova TD, Pawar S, Rogers L, Kolattukudy PE: A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS One 2009, 4:e6077.
  • [57]Berney M, Cook GM: Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia. PLoS One 2010, 5:e8614.
  • [58]Dhiman RK, Mahapatra S, Slayden RA, Boyne ME, Lenaerts A, Hinshaw JC, Angala SK, Chatterjee D, Biswas K, Narayanasamy P, Kurosu M, Crick DC: Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non-replicating persistence. Mol Microbiol 2009, 72:85-97.
  • [59]Russell DG, VanderVen BC, Lee W, Abramovitch RB, Kim M-jeong, Homolka S, Niemann S, Rohde KH: Mycobacterium tuberculosis wears what it eats. Cell Host Microbe 2010, 8:68-76.
  • [60]Betts JC, Lukey PT, Robb LC, McAdam RA, Duncan K: Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 2002, 43:717-731.
  • [61]Voskuil MI, Bartek IL, Visconti K, Schoolnik GK: The response of mycobacterium tuberculosis to reactive oxygen and nitrogen species. Front Microbiol 2011, 2:105.
  • [62]Schnappinger D, Ehrt S, Voskuil MI, Liu Y, Mangan JA, Monahan IM, Dolganov G, Efron B, Butcher PD, Nathan C, Schoolnik GK: Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. J Exp Med 2003, 198:693-704.
  • [63]Velmurugan K, Chen B, Miller JL, Azogue S, Gurses S, Hsu T, Glickman M, Jacobs WR, Porcelli SA, Briken V: Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog 2007, 3:e110.
  • [64]Waddell SJ, Stabler RA, Laing K, Kremer L, Reynolds RC, Besra GS: The use of microarray analysis to determine the gene expression profiles of Mycobacterium tuberculosis in response to anti-bacterial compounds. Tuberculosis (Edinb) 2004, 84:263-274.
  • [65]MacHugh DE, Gormley E, Park SDE, Browne JA, Taraktsoglou M, O'Farrelly C, Meade KG: Gene expression profiling of the host response to Mycobacterium bovis infection in cattle. Transbound Emerg Dis 2009, 56:204-214.
  • [66]Patel D, Danelishvili L, Yamazaki Y, Alonso M, Paustian ML, Bannantine JP, Meunier-Goddik L, Bermudez LE: The ability of Mycobacterium avium subsp. paratuberculosis to enter bovine epithelial cells is influenced by preexposure to a hyperosmolar environment and intracellular passage in bovine mammary epithelial cells. Infect Immun 2006, 74:2849-2855.
  • [67]Tanaka K, Wilks M, Coates PJ, Farthing MJ, Walker-Smith JA, Tabaqchali S: Mycobacterium paratuberculosis and Crohn's disease. Gut 1991, 32:43-45.
  • [68]Naser SA, Ghobrial G, Romero C, Valentine JF: Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn's disease. Lancet 2004, 364:1039-1044.
  • [69]Lundberg JO, Weitzberg E: NO generation from nitrite and its role in vascular control. Arterioscler Thromb Vasc Biol 2005, 25:915-922.
  • [70]Moreno-Vivián C, Cabello P, Martínez-Luque M, Blasco R, Castillo F: Prokaryotic nitrate reduction: molecular properties and functional distinction among bacterial nitrate reductases. J Bacteriol 1999, 181:6573-6584.
  • [71]Loebel RO, Shorr E, Richardson HB: The Influence of Adverse Conditions upon the Respiratory Metabolism and Growth of Human Tubercle Bacilli. J Bacteriol 1933, 26:167-200.
  • [72]Wayne LG, Sohaskey CD: Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol 2001, 55:139-163.
  • [73]McKinney JD, Höner zu Bentrup K, Muñoz-Elías EJ, Miczak A, Chen B, Chan WT, Swenson D, Sacchettini JC, Jacobs WR, Russell DG: Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000, 406:735-738.
  • [74]Wu C-wei, Schmoller SK, Shin SJ, Talaat AM: Defining the stressome of Mycobacterium avium subsp. paratuberculosis in vitro and in naturally infected cows. J Bacteriol 2007, 189:7877-7886.
  • [75]Rengarajan J, Bloom BR, Rubin EJ: Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA 2005, 102:8327-8332.
  • [76]Goding J: Monoclonal antibodies: principles and practice : production and application of monoclonal antibodies in cell biology, biochemistry and immunology. 3rd edition. Academic Press, London; 1996.
  • [77]Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, Haddix PL, Collins HL, Fok AK, Allen RD, Gluck SL, Heuser J, Russell DG: Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 1994, 263:678-681.
  • [78]Domingue GJ, Woody HB: Bacterial persistence and expression of disease. Clin Microbiol Rev 1997, 10:320-344.
  • [79]Hines ME, Styer EL: Preliminary characterization of chemically generated Mycobacterium avium subsp. paratuberculosis cell wall deficient forms (spheroplasts). Vet Microbiol 2003, 95:247-258.
  • [80]Sechi LA, Ahmed N, Felis GE, Duprè I, Cannas S, Fadda G, Bua A, Zanetti S: Immunogenicity and cytoadherence of recombinant heparin binding haemagglutinin (HBHA) of Mycobacterium avium subsp. paratuberculosis: functional promiscuity or a role in virulence? Vaccine 2006, 24:236-243.
  • [81]Rahman A, Srivastava SS, Sneh A, Ahmed N, Krishnasastry MV: Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium tuberculosis: a non-conventional hemolysin and a ribosomal RNA methyl transferase. BMC Biochem 2010, 11:35. BioMed Central Full Text
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