Omics Analysis of Blood-Responsive Regulon in Bordetella pertussis Identifies a Novel Essential T3SS Substrate
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
19-12338S
Grantová Agentura České Republiky
CZ.02.2.69/0.0/0.0/17_050/0008376
Europeam Social Fund
PubMed
33450976
PubMed Central
PMC7828420
DOI
10.3390/ijms22020736
PII: ijms22020736
Knihovny.cz E-zdroje
- Klíčová slova
- Bordetella pertussis, T3SS, blood exposure, gene expression, omics analyses, protein secretion,
- MeSH
- anotace sekvence MeSH
- bakteriální proteiny metabolismus MeSH
- Bordetella pertussis fyziologie MeSH
- chromatografie kapalinová MeSH
- faktory virulence MeSH
- genomika * metody MeSH
- lidé MeSH
- proteomika * metody MeSH
- regulace genové exprese u bakterií MeSH
- sekreční systém typu III genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- tandemová hmotnostní spektrometrie MeSH
- transkriptom MeSH
- virulence MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bakteriální proteiny MeSH
- faktory virulence MeSH
- sekreční systém typu III MeSH
Bacterial pathogens sense specific cues associated with different host niches and integrate these signals to appropriately adjust the global gene expression. Bordetella pertussis is a Gram-negative, strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Though B. pertussis does not cause invasive infections, previous results indicated that this reemerging pathogen responds to blood exposure. Here, omics RNA-seq and LC-MS/MS techniques were applied to determine the blood-responsive regulon of B. pertussis. These analyses revealed that direct contact with blood rewired global gene expression profiles in B. pertussis as the expression of almost 20% of all genes was significantly modulated. However, upon loss of contact with blood, the majority of blood-specific effects vanished, with the exception of several genes encoding the T3SS-secreted substrates. For the first time, the T3SS regulator BtrA was identified in culture supernatants of B. pertussis. Furthermore, proteomic analysis identified BP2259 protein as a novel secreted T3SS substrate, which is required for T3SS functionality. Collectively, presented data indicate that contact with blood represents an important cue for B. pertussis cells.
Zobrazit více v PubMed
Fang F.C., Frawley E.R., Tapscott T., Vazquez-Torres A. Bacterial Stress Responses during Host Infection. Cell Host Microbe. 2016;20:133–143. doi: 10.1016/j.chom.2016.07.009. PubMed DOI PMC
Chauvaux S., Rosso M.L., Frangeul L., Lacroix C., Labarre L., Schiavo A., Marceau M., Dillies M.A., Foulon J., Coppee J.Y., et al. Transcriptome analysis of Yersinia pestis in human plasma: An approach for discovering bacterial genes involved in septicaemic plague. Microbiology. 2007;153:3112–3124. doi: 10.1099/mic.0.2007/006213-0. PubMed DOI
Malachowa N., Whitney A.R., Kobayashi S.D., Sturdevant D.E., Kennedy A.D., Braughton K.R., Shabb D.W., Diep B.A., Chambers H.F., Otto M., et al. Global changes in Staphylococcus aureus gene expression in human blood. PLoS ONE. 2011;6:e18617. doi: 10.1371/journal.pone.0018617. PubMed DOI PMC
Mandlik A., Livny J., Robins W.P., Ritchie J.M., Mekalanos J.J., Waldor M.K. RNA-Seq-based monitoring of infection-linked changes in Vibrio cholerae gene expression. Cell Host Microbe. 2011;10:165–174. doi: 10.1016/j.chom.2011.07.007. PubMed DOI PMC
Mereghetti L., Sitkiewicz I., Green N.M., Musser J.M. Extensive adaptive changes occur in the transcriptome of Streptococcus agalactiae (group B streptococcus) in response to incubation with human blood. PLoS ONE. 2008;3:e3143. doi: 10.1371/journal.pone.0003143. PubMed DOI PMC
Fang F.C., Frawley E.R., Tapscott T., Vazquez-Torres A. Discrimination and Integration of Stress Signals by Pathogenic Bacteria. Cell Host Microbe. 2016;20:144–153. doi: 10.1016/j.chom.2016.07.010. PubMed DOI PMC
Mattoo S., Cherry J.D. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin. Microbiol. Rev. 2005;18:326–382. doi: 10.1128/CMR.18.2.326-382.2005. PubMed DOI PMC
Locht C. Molecular aspects of Bordetella pertussis pathogenesis. Int. Microbiol. Off. J. Span. Soc. Microbiol. 1999;2:137–144. PubMed
Melvin J.A., Scheller E.V., Miller J.F., Cotter P.A. Bordetella pertussis pathogenesis: Current and future challenges. Nat. Rev. Microbiol. 2014;12:274–288. doi: 10.1038/nrmicro3235. PubMed DOI PMC
Guiso N. Bordetella Adenylate Cyclase-Hemolysin Toxins. Toxins. 2017;9:277. doi: 10.3390/toxins9090277. PubMed DOI PMC
Carbonetti N.H. Pertussis toxin and adenylate cyclase toxin: Key virulence factors of Bordetella pertussis and cell biology tools. Future Microbiol. 2010;5:455–469. doi: 10.2217/fmb.09.133. PubMed DOI PMC
Teruya S., Hiramatsu Y., Nakamura K., Fukui-Miyazaki A., Tsukamoto K., Shinoda N., Motooka D., Nakamura S., Ishigaki K., Shinzawa N., et al. Bordetella Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses CaV3.1 as the Cell Surface Receptor. mBio. 2020;11 doi: 10.1128/mBio.03146-19. PubMed DOI PMC
Vojtova J., Kamanova J., Sebo P. Bordetella adenylate cyclase toxin: A swift saboteur of host defense. Curr. Opin. Microbiol. 2006;9:69–75. doi: 10.1016/j.mib.2005.12.011. PubMed DOI
Fennelly N.K., Sisti F., Higgins S.C., Ross P.J., van der Heide H., Mooi F.R., Boyd A., Mills K.H. Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses. Infect. Immun. 2008;76:1257–1266. doi: 10.1128/IAI.00836-07. PubMed DOI PMC
Gaillard M.E., Bottero D., Castuma C.E., Basile L.A., Hozbor D. Laboratory adaptation of Bordetella pertussis is associated with the loss of type three secretion system functionality. Infect. Immun. 2011;79:3677–3682. doi: 10.1128/IAI.00136-11. PubMed DOI PMC
Bibova I., Hot D., Keidel K., Amman F., Slupek S., Cerny O., Gross R., Vecerek B. Transcriptional profiling of Bordetella pertussis reveals requirement of RNA chaperone Hfq for Type III secretion system functionality. RNA Biol. 2015;12:175–185. doi: 10.1080/15476286.2015.1017237. PubMed DOI PMC
Brickman T.J., Cummings C.A., Liew S.Y., Relman D.A., Armstrong S.K. Transcriptional profiling of the iron starvation response in Bordetella pertussis provides new insights into siderophore utilization and virulence gene expression. J. Bacteriol. 2011;193:4798–4812. doi: 10.1128/JB.05136-11. PubMed DOI PMC
Hanawa T., Kamachi K., Yonezawa H., Fukutomi T., Kawakami H., Kamiya S. Glutamate Limitation, BvgAS Activation, and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System. J. Bacteriol. 2016;198:343–351. doi: 10.1128/JB.00596-15. PubMed DOI PMC
Dienstbier A., Amman F., Stipl D., Petrackova D., Vecerek B. Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis. Int. J. Mol. Sci. 2019;20:3073. doi: 10.3390/ijms20123073. PubMed DOI PMC
Dienstbier A., Amman F., Petrackova D., Stipl D., Capek J., Zavadilova J., Fabianova K., Drzmisek J., Kumar D., Wildung M., et al. Comparative Omics Analysis of Historic and Recent Isolates of Bordetella pertussis and Effects of Genome Rearrangements on Evolution. Emerg. Infect. Dis. 2021;27:57–68. doi: 10.3201/eid2701.191541. PubMed DOI PMC
Galan J.E., Lara-Tejero M., Marlovits T.C., Wagner S. Bacterial type III secretion systems: Specialized nanomachines for protein delivery into target cells. Annu. Rev. Microbiol. 2014;68:415–438. doi: 10.1146/annurev-micro-092412-155725. PubMed DOI PMC
French C.T., Panina E.M., Yeh S.H., Griffith N., Arambula D.G., Miller J.F. The Bordetella type III secretion system effector BteA contains a conserved N-terminal motif that guides bacterial virulence factors to lipid rafts. Cell. Microbiol. 2009;11:1735–1749. doi: 10.1111/j.1462-5822.2009.01361.x. PubMed DOI PMC
Kuwae A., Matsuzawa T., Ishikawa N., Abe H., Nonaka T., Fukuda H., Imajoh-Ohmi S., Abe A. BopC is a novel type III effector secreted by Bordetella bronchiseptica and has a critical role in type III-dependent necrotic cell death. J. Biol. Chem. 2006;281:6589–6600. doi: 10.1074/jbc.M512711200. PubMed DOI
Kamanova J. Bordetella Type III Secretion Injectosome and Effector Proteins. Front. Cell Infect. Microbiol. 2020;10:466. doi: 10.3389/fcimb.2020.00466. PubMed DOI PMC
Bayram J., Malcova I., Sinkovec L., Holubova J., Streparola G., Jurnecka D., Kucera J., Sedlacek R., Sebo P., Kamanova J. Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue. PLoS Pathog. 2020;16:e1008512. doi: 10.1371/journal.ppat.1008512. PubMed DOI PMC
Yuk M.H., Harvill E.T., Cotter P.A., Miller J.F. Modulation of host immune responses, induction of apoptosis and inhibition of NF-kappaB activation by the Bordetella type III secretion system. Mol. Microbiol. 2000;35:991–1004. doi: 10.1046/j.1365-2958.2000.01785.x. PubMed DOI
Nagamatsu K., Kuwae A., Konaka T., Nagai S., Yoshida S., Eguchi M., Watanabe M., Mimuro H., Koyasu S., Abe A. Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopN. J. Exp. Med. 2009;206:3073–3088. doi: 10.1084/jem.20090494. PubMed DOI PMC
Abe A., Nishimura R., Kuwae A. Bordetella effector BopN is translocated into host cells via its N-terminal residues. Microbiol. Immunol. 2017;61:206–214. doi: 10.1111/1348-0421.12489. PubMed DOI
Fauconnier A., Veithen A., Gueirard P., Antoine R., Wacheul L., Locht C., Bollen A., Godfroid E. Characterization of the type III secretion locus of Bordetella pertussis. Int. J. Med. Microbiol. 2001;290:693–705. doi: 10.1016/S1438-4221(01)80009-6. PubMed DOI
Mattoo S., Yuk M.H., Huang L.L., Miller J.F. Regulation of type III secretion in Bordetella. Mol. Microbiol. 2004;52:1201–1214. doi: 10.1111/j.1365-2958.2004.04053.x. PubMed DOI
Ahuja U., Shokeen B., Cheng N., Cho Y., Blum C., Coppola G., Miller J.F. Differential regulation of type III secretion and virulence genes in Bordetella pertussis and Bordetella bronchiseptica by a secreted anti-sigma factor. Proc. Natl. Acad. Sci. USA. 2016;113:2341–2348. doi: 10.1073/pnas.1600320113. PubMed DOI PMC
Moon K., Bonocora R.P., Kim D.D., Chen Q., Wade J.T., Stibitz S., Hinton D.M. The BvgAS Regulon of Bordetella pertussis. mBio. 2017;8 doi: 10.1128/mBio.01526-17. PubMed DOI PMC
Chen Q., Stibitz S. The BvgASR virulence regulon of Bordetella pertussis. Curr. Opin. Microbiol. 2019;47:74–81. doi: 10.1016/j.mib.2019.01.002. PubMed DOI
van Beek L.F., de Gouw D., Eleveld M.J., Bootsma H.J., de Jonge M.I., Mooi F.R., Zomer A., Diavatopoulos D.A. Adaptation of Bordetella pertussis to the Respiratory Tract. J. Infect. Dis. 2018;217:1987–1996. doi: 10.1093/infdis/jiy125. PubMed DOI
Wong T.Y., Hall J.M., Nowak E.S., Boehm D.T., Gonyar L.A., Hewlett E.L., Eby J.C., Barbier M., Damron F.H. Analysis of the In Vivo Transcriptome of Bordetella pertussis during Infection of Mice. mSphere. 2019;4 doi: 10.1128/mSphereDirect.00154-19. PubMed DOI PMC
Hester S.E., Lui M., Nicholson T., Nowacki D., Harvill E.T. Identification of a CO2 responsive regulon in Bordetella. PLoS ONE. 2012;7:e47635. doi: 10.1371/journal.pone.0047635. PubMed DOI PMC
Gestal M.C., Rivera I., Howard L.K., Dewan K.K., Soumana I.H., Dedloff M., Nicholson T.L., Linz B., Harvill E.T. Blood or Serum Exposure Induce Global Transcriptional Changes, Altered Antigenic Profile, and Increased Cytotoxicity by Classical Bordetellae. Front. Microbiol. 2018;9:1969. doi: 10.3389/fmicb.2018.01969. PubMed DOI PMC
Petrackova D., Farman M.R., Amman F., Linhartova I., Dienstbier A., Kumar D., Drzmisek J., Hofacker I., Rodriguez M.E., Vecerek B. Transcriptional profiling of human macrophages during infection with Bordetella pertussis. RNA Biol. 2020;17:731–742. doi: 10.1080/15476286.2020.1727694. PubMed DOI PMC
Rivera I., Linz B., Dewan K.K., Ma L., Rice C.A., Kyle D.E., Harvill E.T. Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae. Front. Microbiol. 2019;10:2839. doi: 10.3389/fmicb.2019.02839. PubMed DOI PMC
Amman F., D’Halluin A., Antoine R., Huot L., Bibova I., Keidel K., Slupek S., Bouquet P., Coutte L., Caboche S., et al. Primary transcriptome analysis reveals importance of IS elements for the shaping of the transcriptional landscape of Bordetella pertussis. RNA Biol. 2018;15:967–975. doi: 10.1080/15476286.2018.1462655. PubMed DOI PMC
Iriarte M., Cornelis G.R. Identification of SycN, YscX, and YscY, three new elements of the Yersinia yop virulon. J. Bacteriol. 1999;181:675–680. doi: 10.1128/JB.181.2.675-680.1999. PubMed DOI PMC
Yang H., Shan Z., Kim J., Wu W., Lian W., Zeng L., Xing L., Jin S. Regulatory role of PopN and its interacting partners in type III secretion of Pseudomonas aeruginosa. J. Bacteriol. 2007;189:2599–2609. doi: 10.1128/JB.01680-06. PubMed DOI PMC
Graham M.R., Virtaneva K., Porcella S.F., Barry W.T., Gowen B.B., Johnson C.R., Wright F.A., Musser J.M. Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies. Am. J. Pathol. 2005;166:455–465. doi: 10.1016/S0002-9440(10)62268-7. PubMed DOI PMC
Vebo H.C., Snipen L., Nes I.F., Brede D.A. The transcriptome of the nosocomial pathogen Enterococcus faecalis V583 reveals adaptive responses to growth in blood. PLoS ONE. 2009;4:e7660. doi: 10.1371/journal.pone.0007660. PubMed DOI PMC
Bleackley M.R., Wong A.Y., Hudson D.M., Wu C.H., Macgillivray R.T. Blood iron homeostasis: Newly discovered proteins and iron imbalance. Transfus. Med. Rev. 2009;23:103–123. doi: 10.1016/j.tmrv.2008.12.001. PubMed DOI
Echenique-Rivera H., Muzzi A., Del Tordello E., Seib K.L., Francois P., Rappuoli R., Pizza M., Serruto D. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival. PLoS Pathog. 2011;7:e1002027. doi: 10.1371/journal.ppat.1002027. PubMed DOI PMC
Franca A., Carvalhais V., Maira-Litran T., Vilanova M., Cerca N., Pier G. Alterations in the Staphylococcus epidermidis biofilm transcriptome following interaction with whole human blood. Pathog. Dis. 2014;70:444–448. doi: 10.1111/2049-632X.12130. PubMed DOI
Gorringe A.R., Vaughan T.E. Bordetella pertussis fimbriae (Fim): Relevance for vaccines. Expert Rev. Vaccines. 2014;13:1205–1214. doi: 10.1586/14760584.2014.930667. PubMed DOI
Ogawa T., Asai Y., Hashimoto M., Uchida H. Bacterial fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. Eur. J. Immunol. 2002;32:2543–2550. doi: 10.1002/1521-4141(200209)32:9<2543::AID-IMMU2543>3.0.CO;2-2. PubMed DOI
Kalferstova L., Kolar M., Fila L., Vavrova J., Drevinek P. Gene expression profiling of Burkholderia cenocepacia at the time of cepacia syndrome: Loss of motility as a marker of poor prognosis? J. Clin. Microbiol. 2015;53:1515–1522. doi: 10.1128/JCM.03605-14. PubMed DOI PMC
Bheda P. Metabolic transcriptional memory. Mol. Metab. 2020;38:100955. doi: 10.1016/j.molmet.2020.01.019. PubMed DOI PMC
Kurushima J., Kuwae A., Abe A. The type III secreted protein BspR regulates the virulence genes in Bordetella bronchiseptica. PLoS ONE. 2012;7:e38925. doi: 10.1371/journal.pone.0038925. PubMed DOI PMC
Updegrove T.B., Zhang A., Storz G. Hfq: The flexible RNA matchmaker. Curr. Opin. Microbiol. 2016;30:133–138. doi: 10.1016/j.mib.2016.02.003. PubMed DOI PMC
Chao Y., Vogel J. The role of Hfq in bacterial pathogens. Curr. Opin. Microbiol. 2010;13:24–33. doi: 10.1016/j.mib.2010.01.001. PubMed DOI
Feliciano J.R., Grilo A.M., Guerreiro S.I., Sousa S.A., Leitao J.H. Hfq: A multifaceted RNA chaperone involved in virulence. Future Microbiol. 2016;11:137–151. doi: 10.2217/fmb.15.128. PubMed DOI
Bibova I., Skopova K., Masin J., Cerny O., Hot D., Sebo P., Vecerek B. The RNA chaperone Hfq is required for virulence of Bordetella pertussis. Infect. Immun. 2013;81:4081–4090. doi: 10.1128/IAI.00345-13. PubMed DOI PMC
Hot D., Slupek S., Wulbrecht B., D’Hondt A., Hubans C., Antoine R., Locht C., Lemoine Y. Detection of small RNAs in Bordetella pertussis and identification of a novel repeated genetic element. BMC Genom. 2011;12:207. doi: 10.1186/1471-2164-12-207. PubMed DOI PMC
Keidel K., Amman F., Bibova I., Drzmisek J., Benes V., Hot D., Vecerek B. Signal transduction-dependent small regulatory RNA is involved in glutamate metabolism of the human pathogen Bordetella pertussis. RNA. 2018;24:1530–1541. doi: 10.1261/rna.067306.118. PubMed DOI PMC
CDC Fatal case of unsuspected pertussis diagnosed from a blood culture—Minnesota, 2003. Mmwr. Morb. Mortal. Wkly. Rep. 2004;53:131–132. PubMed
Janda W.M., Santos E., Stevens J., Celig D., Terrile L., Schreckenberger P.C. Unexpected isolation of Bordetella pertussis from a blood culture. J. Clin. Microbiol. 1994;32:2851–2853. doi: 10.1128/JCM.32.11.2851-2853.1994. PubMed DOI PMC
Troseid M., Jonassen T.O., Steinbakk M. Isolation of Bordetella pertussis in blood culture from a patient with multiple myeloma. J. Infect. 2006;52:e11–e13. doi: 10.1016/j.jinf.2005.04.014. PubMed DOI
Kasuga T., Nakase Y., Ukishima K., Takatsu K. Studies on Haemophilis pertussis. III. Some properties of each phase of H. pertussis. Kitasato Arch. Exp. Med. 1954;27:37–47. PubMed
Stainer D.W., Scholte M.J. A simple chemically defined medium for the production of phase I Bordetella pertussis. J. Gen. Microbiol. 1970;63:211–220. doi: 10.1099/00221287-63-2-211. PubMed DOI
Bolger A.M., Lohse M., Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–2120. doi: 10.1093/bioinformatics/btu170. PubMed DOI PMC
Patro R., Duggal G., Love M.I., Irizarry R.A., Kingsford C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods. 2017;14:417–419. doi: 10.1038/nmeth.4197. PubMed DOI PMC
Risso D., Ngai J., Speed T.P., Dudoit S. Normalization of RNA-seq data using factor analysis of control genes or samples. Nat. Biotechnol. 2014;32:896–902. doi: 10.1038/nbt.2931. PubMed DOI PMC
Love M.I., Huber W., Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. doi: 10.1186/s13059-014-0550-8. PubMed DOI PMC
Supek F., Bosnjak M., Skunca N., Smuc T. REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS ONE. 2011;6:e21800. doi: 10.1371/journal.pone.0021800. PubMed DOI PMC
Pfaffl M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45. doi: 10.1093/nar/29.9.e45. PubMed DOI PMC
Cox J., Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 2008;26:1367–1372. doi: 10.1038/nbt.1511. PubMed DOI
Cox J., Neuhauser N., Michalski A., Scheltema R.A., Olsen J.V., Mann M. Andromeda: A peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 2011;10:1794–1805. doi: 10.1021/pr101065j. PubMed DOI
Cox J., Hein M.Y., Luber C.A., Paron I., Nagaraj N., Mann M. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell. Proteom. 2014;13:2513–2526. doi: 10.1074/mcp.M113.031591. PubMed DOI PMC
Tyanova S., Temu T., Sinitcyn P., Carlson A., Hein M.Y., Geiger T., Mann M., Cox J. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods. 2016;13:731–740. doi: 10.1038/nmeth.3901. PubMed DOI
Perez-Riverol Y., Csordas A., Bai J., Bernal-Llinares M., Hewapathirana S., Kundu D.J., Inuganti A., Griss J., Mayer G., Eisenacher M., et al. The PRIDE database and related tools and resources in 2019: Improving support for quantification data. Nucleic Acids Res. 2019;47:D442–D450. doi: 10.1093/nar/gky1106. PubMed DOI PMC
Inatsuka C.S., Xu Q., Vujkovic-Cvijin I., Wong S., Stibitz S., Miller J.F., Cotter P.A. Pertactin is required for Bordetella species to resist neutrophil-mediated clearance. Infect. Immun. 2010;78:2901–2909. doi: 10.1128/IAI.00188-10. PubMed DOI PMC