1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Single-Cell Metabolism and Stress Responses in Complex Host Tissues

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Author: Dirk Bumann1
  • Editors: Pascale Cossart2, Craig R. Roy3, Philippe Sansonetti4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland; 2: Institut Pasteur, Paris, France; 3: Yale University School of Medicine, New Haven, Connecticut; 4: Institut Pasteur, Paris, France
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0009-2019
  • Received 27 April 2018 Accepted 18 January 2019 Published 05 April 2019
  • Dirk Bumann, [email protected]
image of <span class="jp-italic">Salmonella</span> Single-Cell Metabolism and Stress Responses in Complex Host Tissues
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Single-Cell Metabolism and Stress Responses in Complex Host Tissues, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/7/2/BAI-0009-2019-1.gif /docserver/preview/fulltext/microbiolspec/7/2/BAI-0009-2019-2.gif
  • Abstract:

    Systemic infections are a major cause of mortality worldwide and are becoming increasingly untreatable. Recent single-cell data from a mouse model of typhoid fever show that the host immune system actually eradicates many cells, while other organisms thrive at the same time in the same tissue, causing lethal disease progression. The surviving cells have highly heterogeneous metabolism, growth rates, and exposure to various stresses. Emerging evidence suggests that similarly heterogeneous host-pathogen encounters might be a key feature of many infectious diseases. This heterogeneity offers fascinating opportunities for research and application. If we understand the mechanisms that determine the disparate local outcomes, we might be able to develop entirely novel strategies for infection control by broadening successful host antimicrobial attacks and closing permissive niches in which pathogens can thrive. This review describes suitable technologies, a current working model of heterogeneous host- interactions, the impact of diverse subsets on antimicrobial chemotherapy, and major open questions and challenges.

  • Citation: Bumann D. 2019. Single-Cell Metabolism and Stress Responses in Complex Host Tissues. Microbiol Spectrum 7(2):BAI-0009-2019. doi:10.1128/microbiolspec.BAI-0009-2019.

References

1. Lozano R, et al. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2095–2128. ERRATUM Lancet 381:628 http://dx.doi.org/10.1016/S0140-6736(12)61728-0.
2. Zinkernagel RM, Hengartner H. 2004. On immunity against infections and vaccines: credo 2004. Scand J Immunol 60:9–13 http://dx.doi.org/10.1111/j.0300-9475.2004.01460.x. [PubMed]
3. Kaufmann SH. 2007. The contribution of immunology to the rational design of novel antibacterial vaccines. Nat Rev Microbiol 5:491–504 http://dx.doi.org/10.1038/nrmicro1688. [PubMed]
4. Epstein JE, Giersing B, Mullen G, Moorthy V, Richie TL. 2007. Malaria vaccines: are we getting closer? Curr Opin Mol Ther 9:12–24. [PubMed]
5. Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE Jr. 2004. Trends in antimicrobial drug development: implications for the future. Clin Infect Dis 38:1279–1286 http://dx.doi.org/10.1086/420937. [PubMed]
6. Norrby SR, Nord CE, Finch R, European Society of Clinical Microbiology and Infectious Diseases. 2005. Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancet Infect Dis 5:115–119 http://dx.doi.org/10.1016/S1473-3099(05)70086-4.
7. Kaldalu N, Hauryliuk V, Tenson T. 2016. Persisters—as elusive as ever. Appl Microbiol Biotechnol 100:6545–6553 http://dx.doi.org/10.1007/s00253-016-7648-8. [PubMed]
8. Rowe SE, Conlon BP, Keren I, Lewis K. 2016. Persisters: methods for isolation and identifying contributing factors—a review. Methods Mol Biol 1333:17–28 http://dx.doi.org/10.1007/978-1-4939-2854-5_2. [PubMed]
9. Balaban NQ, Gerdes K, Lewis K, McKinney JD. 2013. A problem of persistence: still more questions than answers? Nat Rev Microbiol 11:587–591 http://dx.doi.org/10.1038/nrmicro3076. [PubMed]
10. Maisonneuve E, Gerdes K. 2014. Molecular mechanisms underlying bacterial persisters. Cell 157:539–548 http://dx.doi.org/10.1016/j.cell.2014.02.050. [PubMed]
11. Davis KM, Isberg RR. 2016. Defining heterogeneity within bacterial populations via single cell approaches. BioEssays 38:782–790 http://dx.doi.org/10.1002/bies.201500121. [PubMed]
12. Bumann D. 2015. Heterogeneous host-pathogen encounters: act locally, think globally. Cell Host Microbe 17:13–19 http://dx.doi.org/10.1016/j.chom.2014.12.006. [PubMed]
13. Kreibich S, Hardt WD. 2015. Experimental approaches to phenotypic diversity in infection. Curr Opin Microbiol 27:25–36 http://dx.doi.org/10.1016/j.mib.2015.06.007. [PubMed]
14. Prideaux B, Via LE, Zimmerman MD, Eum S, Sarathy J, O’Brien P, Chen C, Kaya F, Weiner DM, Chen PY, Song T, Lee M, Shim TS, Cho JS, Kim W, Cho SN, Olivier KN, Barry CE III, Dartois V. 2015. The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med 21:1223–1227 http://dx.doi.org/10.1038/nm.3937. [PubMed]
15. Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, DePalatis L, Raab H, Hazenbos WL, Morisaki JH, Kim J, Park S, Darwish M, Lee BC, Hernandez H, Loyet KM, Lupardus P, Fong R, Yan D, Chalouni C, Luis E, Khalfin Y, Plise E, Cheong J, Lyssikatos JP, Strandh M, Koefoed K, Andersen PS, Flygare JA, Wah Tan M, Brown EJ, Mariathasan S. 2015. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527:323–328 http://dx.doi.org/10.1038/nature16057. [PubMed]
16. Brauner A, Fridman O, Gefen O, Balaban NQ. 2016. Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol 14:320–330 http://dx.doi.org/10.1038/nrmicro.2016.34. [PubMed]
17. Malherbe ST, Shenai S, Ronacher K, Loxton AG, Dolganov G, Kriel M, Van T, Chen RY, Warwick J, Via LE, Song T, Lee M, Schoolnik G, Tromp G, Alland D, Barry CE III, Winter J, Walzl G, Lucas L, van der Spuy G, Stanley K, Thiart L, Smith B, Du Plessis N, Beltran CG, Maasdorp E, Ellmann A, Choi H, Joh J, Dodd LE, Allwood B, Koegelenberg C, Vorster M, Griffith-Richards S, Catalysis TB–Biomarker Consortium. 2016. Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat Med 22:1094–1100. CORRIGENDUM Nat Med 23:526. CORRIGENDUM Nat Med 23:1499. http://dx.doi.org/10.1038/nm.4177.
18. Lenaerts A, Barry CE III, Dartois V. 2015. Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Immunol Rev 264:288–307 http://dx.doi.org/10.1111/imr.12252. [PubMed]
19. Marakalala MJ, Raju RM, Sharma K, Zhang YJ, Eugenin EA, Prideaux B, Daudelin IB, Chen PY, Booty MG, Kim JH, Eum SY, Via LE, Behar SM, Barry CE III, Mann M, Dartois V, Rubin EJ. 2016. Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat Med 22:531–538 http://dx.doi.org/10.1038/nm.4073. [PubMed]
20. Diard M, Garcia V, Maier L, Remus-Emsermann MN, Regoes RR, Ackermann M, Hardt WD. 2013. Stabilization of cooperative virulence by the expression of an avirulent phenotype. Nature 494:353–356 http://dx.doi.org/10.1038/nature11913. [PubMed]
21. Ackermann M, Stecher B, Freed NE, Songhet P, Hardt WD, Doebeli M. 2008. Self-destructive cooperation mediated by phenotypic noise. Nature 454:987–990 http://dx.doi.org/10.1038/nature07067. [PubMed]
22. Burton NA, Schürmann N, Casse O, Steeb AK, Claudi B, Zankl J, Schmidt A, Bumann D. 2014. Disparate impact of oxidative host defenses determines the fate of Salmonella during systemic infection in mice. Cell Host Microbe 15:72–83 http://dx.doi.org/10.1016/j.chom.2013.12.006. [PubMed]
23. Davis KM, Mohammadi S, Isberg RR. 2015. Community behavior and spatial regulation within a bacterial microcolony in deep tissue sites serves to protect against host attack. Cell Host Microbe 17:21–31 http://dx.doi.org/10.1016/j.chom.2014.11.008. [PubMed]
24. Alemany A, Florescu M, Baron CS, Peterson-Maduro J, van Oudenaarden A. 2018. Whole-organism clone tracing using single-cell sequencing. Nature 556:108–112 http://dx.doi.org/10.1038/nature25969. [PubMed]
25. Saliba AE, Santos SC, Vogel J. 2017. New RNA-seq approaches for the study of bacterial pathogens. Curr Opin Microbiol 35:78–87 http://dx.doi.org/10.1016/j.mib.2017.01.001. [PubMed]
26. Kang Y, McMillan I, Norris MH, Hoang TT. 2015. Single prokaryotic cell isolation and total transcript amplification protocol for transcriptomic analysis. Nat Protoc 10:974–984 http://dx.doi.org/10.1038/nprot.2015.058. [PubMed]
27. Avital G, Avraham R, Fan A, Hashimshony T, Hung DT, Yanai I. 2017. scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing. Genome Biol 18:200 http://dx.doi.org/10.1186/s13059-017-1340-x. [PubMed]
28. Chong S, Chen C, Ge H, Xie XS. 2014. Mechanism of transcriptional bursting in bacteria. Cell 158:314–326 http://dx.doi.org/10.1016/j.cell.2014.05.038. [PubMed]
29. Taniguchi Y, Choi PJ, Li GW, Chen H, Babu M, Hearn J, Emili A, Xie XS. 2010. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science 329:533–538 http://dx.doi.org/10.1126/science.1188308. [PubMed]
30. Zhang L, Vertes A. 2017. Single-cell mass spectrometry approaches to explore cellular heterogeneity. Angew Chem Int Ed Engl 57:4466–4477. [PubMed]
31. Khan SM, Franke-Fayard B, Mair GR, Lasonder E, Janse CJ, Mann M, Waters AP. 2005. Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology. Cell 121:675–687 http://dx.doi.org/10.1016/j.cell.2005.03.027. [PubMed]
32. Ackermann M. 2015. A functional perspective on phenotypic heterogeneity in microorganisms. Nat Rev Microbiol 13:497–508 http://dx.doi.org/10.1038/nrmicro3491. [PubMed]
33. Rodriguez EA, Campbell RE, Lin JY, Lin MZ, Miyawaki A, Palmer AE, Shu X, Zhang J, Tsien RY. 2017. The growing and glowing toolbox of fluorescent and photoactive proteins. Trends Biochem Sci 42:111–129 http://dx.doi.org/10.1016/j.tibs.2016.09.010. [PubMed]
34. Bumann D. 2002. Examination of Salmonella gene expression in an infected mammalian host using the green fluorescent protein and two-colour flow cytometry. Mol Microbiol 43:1269–1283 http://dx.doi.org/10.1046/j.1365-2958.2002.02821.x. [PubMed]
35. Müller AJ, Aeschlimann S, Olekhnovitch R, Dacher M, Späth GF, Bousso P. 2013. Photoconvertible pathogen labeling reveals nitric oxide control of Leishmania major infection in vivo via dampening of parasite metabolism. Cell Host Microbe 14:460–467 http://dx.doi.org/10.1016/j.chom.2013.09.008. [PubMed]
36. Rollenhagen C, Sörensen M, Rizos K, Hurvitz R, Bumann D. 2004. Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen. Proc Natl Acad Sci USA 101:8739–8744 http://dx.doi.org/10.1073/pnas.0401283101. [PubMed]
37. Bonde MT, Pedersen M, Klausen MS, Jensen SI, Wulff T, Harrison S, Nielsen AT, Herrgård MJ, Sommer MO. 2016. Predictable tuning of protein expression in bacteria. Nat Methods 13:233. [PubMed]
38. Wendland M, Bumann D. 2002. Optimization of GFP levels for analyzing Salmonella gene expression during an infection. FEBS Lett 521:105–108 http://dx.doi.org/10.1016/S0014-5793(02)02834-X.
39. Rang C, Galen JE, Kaper JB, Chao L. 2003. Fitness cost of the green fluorescent protein in gastrointestinal bacteria. Can J Microbiol 49:531–537 http://dx.doi.org/10.1139/w03-072. [PubMed]
40. Bienick MS, Young KW, Klesmith JR, Detwiler EE, Tomek KJ, Whitehead TA. 2014. The interrelationship between promoter strength, gene expression, and growth rate. PLoS One 9:e109105 http://dx.doi.org/10.1371/journal.pone.0109105. [PubMed]
41. Knodler LA, Bestor A, Ma C, Hansen-Wester I, Hensel M, Vallance BA, Steele-Mortimer O. 2005. Cloning vectors and fluorescent proteins can significantly inhibit Salmonella enterica virulence in both epithelial cells and macrophages: implications for bacterial pathogenesis studies. Infect Immun 73:7027–7031 http://dx.doi.org/10.1128/IAI.73.10.7027-7031.2005. [PubMed]
42. Ceroni F, Algar R, Stan G-B, Ellis T. 2015. Quantifying cellular capacity identifies gene expression designs with reduced burden. Nat Methods 12:415–418 http://dx.doi.org/10.1038/nmeth.3339. [PubMed]
43. Lee EJ, Pontes MH, Groisman EA. 2013. A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium’s own F 1F o ATP synthase. Cell 154:146–156 http://dx.doi.org/10.1016/j.cell.2013.06.004. [PubMed]
44. Maglica Ž, Özdemir E, McKinney JD. 2015. Single-cell tracking reveals antibiotic-induced changes in mycobacterial energy metabolism. mBio 6:e02236-14 http://dx.doi.org/10.1128/mBio.02236-14. [PubMed]
45. van der Heijden J, Bosman ES, Reynolds LA, Finlay BB. 2015. Direct measurement of oxidative and nitrosative stress dynamics in Salmonella inside macrophages. Proc Natl Acad Sci USA 112:560–565 http://dx.doi.org/10.1073/pnas.1414569112. [PubMed]
46. Barat S, Willer Y, Rizos K, Claudi B, Mazé A, Schemmer AK, Kirchhoff D, Schmidt A, Burton N, Bumann D. 2012. Immunity to intracellular Salmonella depends on surface-associated antigens. PLoS Pathog 8:e1002966 http://dx.doi.org/10.1371/journal.ppat.1002966. [PubMed]
47. Roostalu J, Jõers A, Luidalepp H, Kaldalu N, Tenson T. 2008. Cell division in Escherichia coli cultures monitored at single cell resolution. BMC Microbiol 8:68 http://dx.doi.org/10.1186/1471-2180-8-68. [PubMed]
48. Helaine S, Thompson JA, Watson KG, Liu M, Boyle C, Holden DW. 2010. Dynamics of intracellular bacterial replication at the single cell level. Proc Natl Acad Sci USA 107:3746–3751 http://dx.doi.org/10.1073/pnas.1000041107. [PubMed]
49. Saliba AE, Li L, Westermann AJ, Appenzeller S, Stapels DA, Schulte LN, Helaine S, Vogel J. 2016. Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella. Nat Microbiol 2:16206 http://dx.doi.org/10.1038/nmicrobiol.2016.206. [PubMed]
50. Helaine S, Cheverton AM, Watson KG, Faure LM, Matthews SA, Holden DW. 2014. Internalization of Salmonella by macrophages induces formation of nonreplicating persisters. Science 343:204–208 http://dx.doi.org/10.1126/science.1244705. [PubMed]
51. Terskikh A, Fradkov A, Ermakova G, Zaraisky A, Tan P, Kajava AV, Zhao X, Lukyanov S, Matz M, Kim S, Weissman I, Siebert P. 2000. “Fluorescent timer”: protein that changes color with time. Science 290:1585–1588 http://dx.doi.org/10.1126/science.290.5496.1585. [PubMed]
52. Claudi B, Spröte P, Chirkova A, Personnic N, Zankl J, Schürmann N, Schmidt A, Bumann D. 2014. Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy. Cell 158:722–733 http://dx.doi.org/10.1016/j.cell.2014.06.045. [PubMed]
53. Strack RL, Strongin DE, Mets L, Glick BS, Keenan RJ. 2010. Chromophore formation in DsRed occurs by a branched pathway. J Am Chem Soc 132:8496–8505 http://dx.doi.org/10.1021/ja1030084. [PubMed]
54. Manina G, Dhar N, McKinney JD. 2015. Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms. Cell Host Microbe 17:32–46 http://dx.doi.org/10.1016/j.chom.2014.11.016. [PubMed]
55. Etzel M, Mörl M. 2017. Synthetic riboswitches: from plug and pray toward plug and play. Biochemistry 56:1181–1198 http://dx.doi.org/10.1021/acs.biochem.6b01218. [PubMed]
56. Curkić I, Schütz M, Oberhettinger P, Diard M, Claassen M, Linke D, Hardt WD. 2016. Epitope-tagged autotransporters as single-cell reporters for gene expression by a Salmonella Typhimurium wbaP mutant. PLoS One 11:e0154828 http://dx.doi.org/10.1371/journal.pone.0154828. [PubMed]
57. Kaiser P, Regoes RR, Dolowschiak T, Wotzka SY, Lengefeld J, Slack E, Grant AJ, Ackermann M, Hardt WD. 2014. Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment. PLoS Biol 12:e1001793 http://dx.doi.org/10.1371/journal.pbio.1001793. [PubMed]
58. Ao TT, Feasey NA, Gordon MA, Keddy KH, Angulo FJ, Crump JA. 2015. Global burden of invasive nontyphoidal Salmonella disease, 2010. Emerg Infect Dis 21:941–949 http://dx.doi.org/10.3201/eid2106.140999. [PubMed]
59. Crump JA, Luby SP, Mintz ED. 2004. The global burden of typhoid fever. Bull World Health Organ 82:346–353. [PubMed]
60. Marks F, et al. 2017. Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study. Lancet Glob Health 5:e310–e323 http://dx.doi.org/10.1016/S2214-109X(17)30022-0.
61. Mogasale V, Maskery B, Ochiai RL, Lee JS, Mogasale VV, Ramani E, Kim YE, Park JK, Wierzba TF. 2014. Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment. Lancet Glob Health 2:e570–e580 http://dx.doi.org/10.1016/S2214-109X(14)70301-8.
62. Wain J, Hendriksen RS, Mikoleit ML, Keddy KH, Ochiai RL. 2015. Typhoid fever. Lancet 385:1136–1145 http://dx.doi.org/10.1016/S0140-6736(13)62708-7.
63. Levine MM, Simon R. 2018. The gathering storm: is untreatable typhoid fever on the way? mBio 9:e00482-18 http://dx.doi.org/10.1128/mBio.00482-18. [PubMed]
64. Kariuki S, Gordon MA, Feasey N, Parry CM. 2015. Antimicrobial resistance and management of invasive Salmonella disease. Vaccine 33(Suppl 3) :C21–C29 http://dx.doi.org/10.1016/j.vaccine.2015.03.102. [PubMed]
65. Tsolis RM, Xavier MN, Santos RL, Bäumler AJ. 2011. How to become a top model: impact of animal experimentation on human Salmonella disease research. Infect Immun 79:1806–1814 http://dx.doi.org/10.1128/IAI.01369-10. [PubMed]
66. Helaine S, Kugelberg E. 2014. Bacterial persisters: formation, eradication, and experimental systems. Trends Microbiol 22:417–424 http://dx.doi.org/10.1016/j.tim.2014.03.008. [PubMed]
67. Bumann D, Cunrath O. 2017. Heterogeneity of Salmonella-host interactions in infected host tissues. Curr Opin Microbiol 39:57–63 http://dx.doi.org/10.1016/j.mib.2017.09.008. [PubMed]
68. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG, Inflammation and Host Response to Injury, Large Scale Collaborative Research Program. 2013. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 110:3507–3512 http://dx.doi.org/10.1073/pnas.1222878110. [PubMed]
69. Takao K, Miyakawa T. 2015. Genomic responses in mouse models greatly mimic human inflammatory diseases. Proc Natl Acad Sci USA 112:1167–1172 CORRECTION Proc Natl Acad Sci USA 112:E1163–E1167 http://dx.doi.org/10.1073/pnas.1401965111.
70. Kola I, Landis J. 2004. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711–716 http://dx.doi.org/10.1038/nrd1470. [PubMed]
71. Bumann D, Hueck C, Aebischer T, Meyer TF. 2000. Recombinant live Salmonella spp. for human vaccination against heterologous pathogens. FEMS Immunol Med Microbiol 27:357–364 http://dx.doi.org/10.1111/j.1574-695X.2000.tb01450.x. [PubMed]
72. Dougan G, John V, Palmer S, Mastroeni P. 2011. Immunity to salmonellosis. Immunol Rev 240:196–210 http://dx.doi.org/10.1111/j.1600-065X.2010.00999.x. [PubMed]
73. Meunier E, Dick MS, Dreier RF, Schürmann N, Kenzelmann Broz D, Warming S, Roose-Girma M, Bumann D, Kayagaki N, Takeda K, Yamamoto M, Broz P. 2014. Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature 509:366–370 http://dx.doi.org/10.1038/nature13157. [PubMed]
74. Schürmann N, Forrer P, Casse O, Li J, Felmy B, Burgener AV, Ehrenfeuchter N, Hardt WD, Recher M, Hess C, Tschan-Plessl A, Khanna N, Bumann D. 2017. Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage. Nat Microbiol 2:16268 http://dx.doi.org/10.1038/nmicrobiol.2016.268. [PubMed]
75. Sheppard M, Webb C, Heath F, Mallows V, Emilianus R, Maskell D, Mastroeni P. 2003. Dynamics of bacterial growth and distribution within the liver during Salmonella infection. Cell Microbiol 5:593–600 http://dx.doi.org/10.1046/j.1462-5822.2003.00296.x. [PubMed]
76. Kupz A, Scott TA, Belz GT, Andrews DM, Greyer M, Lew AM, Brooks AG, Smyth MJ, Curtiss R III, Bedoui S, Strugnell RA. 2013. Contribution of Thy1+ NK cells to protective IFN-γ production during Salmonella typhimurium infections. Proc Natl Acad Sci USA 110:2252–2257 http://dx.doi.org/10.1073/pnas.1222047110. [PubMed]
77. Pilonieta MC, Moreland SM, English CN, Detweiler CS. 2014. Salmonella enterica infection stimulates macrophages to hemophagocytose. mBio 5:e02211-14 http://dx.doi.org/10.1128/mBio.02211-14. [PubMed]
78. Steeb B, Claudi B, Burton NA, Tienz P, Schmidt A, Farhan H, Mazé A, Bumann D. 2013. Parallel exploitation of diverse host nutrients enhances Salmonella virulence. PLoS Pathog 9:e1003301 http://dx.doi.org/10.1371/journal.ppat.1003301. [PubMed]
79. Mastroeni P, Vazquez-Torres A, Fang FC, Xu Y, Khan S, Hormaeche CE, Dougan G. 2000. Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation and host survival in vivo. J Exp Med 192:237–248 http://dx.doi.org/10.1084/jem.192.2.237. [PubMed]
80. Aussel L, Zhao W, Hébrard M, Guilhon AA, Viala JP, Henri S, Chasson L, Gorvel JP, Barras F, Méresse S. 2011. Salmonella detoxifying enzymes are sufficient to cope with the host oxidative burst. Mol Microbiol 80:628–640 http://dx.doi.org/10.1111/j.1365-2958.2011.07611.x. [PubMed]
81. McCormack RM, de Armas LR, Shiratsuchi M, Fiorentino DG, Olsson ML, Lichtenheld MG, Morales A, Lyapichev K, Gonzalez LE, Strbo N, Sukumar N, Stojadinovic O, Plano GV, Munson GP, Tomic-Canic M, Kirsner RS, Russell DG, Podack ER. 2015. Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. eLife 4:e06508 http://dx.doi.org/10.7554/eLife.06508. [PubMed]
82. Thöne F, Schwanhäusser B, Becker D, Ballmaier M, Bumann D. 2007. FACS-isolation of Salmonella-infected cells with defined bacterial load from mouse spleen. J Microbiol Methods 71:220–224 http://dx.doi.org/10.1016/j.mimet.2007.08.016. [PubMed]
83. Brown SP, Cornell SJ, Sheppard M, Grant AJ, Maskell DJ, Grenfell BT, Mastroeni P. 2006. Intracellular demography and the dynamics of Salmonella enterica infections. PLoS Biol 4:e349 http://dx.doi.org/10.1371/journal.pbio.0040349. [PubMed]
84. McLaughlin LM, Xu H, Carden SE, Fisher S, Reyes M, Heilshorn SC, Monack DM. 2014. A microfluidic-based genetic screen to identify microbial virulence factors that inhibit dendritic cell migration. Integr Biol 6:438–449 http://dx.doi.org/10.1039/C3IB40177D. [PubMed]
85. Worley MJ, Nieman GS, Geddes K, Heffron F. 2006. Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. Proc Natl Acad Sci USA 103:17915–17920 http://dx.doi.org/10.1073/pnas.0604054103. [PubMed]
86. Hughes D, Andersson DI. 2017. Environmental and genetic modulation of the phenotypic expression of antibiotic resistance. FEMS Microbiol Rev 41:374–391 http://dx.doi.org/10.1093/femsre/fux004. [PubMed]
87. Onufrak NJ, Forrest A, Gonzalez D. 2016. Pharmacokinetic and pharmacodynamic principles of anti-infective dosing. Clin Ther 38:1930–1947 http://dx.doi.org/10.1016/j.clinthera.2016.06.015. [PubMed]
88. Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, Bergstedt J, Charbit B, Rouilly V, MacPherson CR, Hasan M, Albaud B, Gentien D, Fellay J, Albert ML, Quintana-Murci L, Milieu Intérieur Consortium. 2018. Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. Proc Natl Acad Sci USA 115:E488–E497 http://dx.doi.org/10.1073/pnas.1714765115. [PubMed]
89. Brodin P, Davis MM. 2017. Human immune system variation. Nat Rev Immunol 17:21–29 http://dx.doi.org/10.1038/nri.2016.125. [PubMed]
90. Conlon BP. 2014. Staphylococcus aureus chronic and relapsing infections: evidence of a role for persister cells. BioEssays 36:991–996 http://dx.doi.org/10.1002/bies.201400080. [PubMed]
91. World Health Organization. 2006. Brucellosis in Humans and Animals. World Health Organization, Geneva, Switzerland. www.who.int/csr/resources/publications/Brucellosis.pdf.
92. Guglietta A. 2017. Recurrent urinary tract infections in women: risk factors, etiology, pathogenesis and prophylaxis. Future Microbiol 12:239–246 http://dx.doi.org/10.2217/fmb-2016-0145. [PubMed]
93. Onwuezobe IA, Oshun PO, Odigwe CC. 2012. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev 11:CD001167.
94. DePas WH, Starwalt-Lee R, Van Sambeek L, Ravindra Kumar S, Gradinaru V, Newman DK. 2016. Exposing the three-dimensional biogeography and metabolic states of pathogens in cystic fibrosis sputum via hydrogel embedding, clearing, and rRNA labeling. mBio 7:e00796-16 http://dx.doi.org/10.1128/mBio.00796-16.
95. Cronan MR, Rosenberg AF, Oehlers SH, Saelens JW, Sisk DM, Jurcic Smith KL, Lee S, Tobin DM. 2015. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections. Dis Model Mech 8:1643–1650 http://dx.doi.org/10.1242/dmm.021394. [PubMed]
96. Arena ET, Campbell-Valois F-X, Tinevez J-Y, Nigro G, Sachse M, Moya-Nilges M, Nothelfer K, Marteyn B, Shorte SL, Sansonetti PJ. 2015. Bioimage analysis of Shigella infection reveals targeting of colonic crypts. Proc Natl Acad Sci USA 112:E3282–E3290 http://dx.doi.org/10.1073/pnas.1509091112. [PubMed]
97. Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Yang JL, Ferrante TC, Terry R, Jeanty SS, Li C, Amamoto R, Peters DT, Turczyk BM, Marblestone AH, Inverso SA, Bernard A, Mali P, Rios X, Aach J, Church GM. 2014. Highly multiplexed subcellular RNA sequencing in situ. Science 343:1360–1363 http://dx.doi.org/10.1126/science.1250212. [PubMed]
98. Halpern KB, Shenhav R, Matcovitch-Natan O, Tóth B, Lemze D, Golan M, Massasa EE, Baydatch S, Landen S, Moor AE, Brandis A, Giladi A, Stokar-Avihail AS, David E, Amit I, Itzkovitz S. 2017. Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature 542:352–356 ERRATUM Nature 543:742 http://dx.doi.org/10.1038/nature21065.
99. Müller AJ, Kaiser P, Dittmar KE, Weber TC, Haueter S, Endt K, Songhet P, Zellweger C, Kremer M, Fehling HJ, Hardt WD. 2012. Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes. Cell Host Microbe 11:19–32 http://dx.doi.org/10.1016/j.chom.2011.11.013. [PubMed]
100. Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, Germain RN. 2011. Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity 34:807–819 http://dx.doi.org/10.1016/j.immuni.2011.03.022. [PubMed]
101. Choong FX, Richter-Dahlfors A. 2014. Intravital two-photon imaging to understand bacterial infections of the mammalian host. Methods Mol Biol 1197:87–100 http://dx.doi.org/10.1007/978-1-4939-1261-2_5. [PubMed]
102. Ramakrishnan L. 2013. The zebrafish guide to tuberculosis immunity and treatment. Cold Spring Harb Symp Quant Biol 78:179–192 http://dx.doi.org/10.1101/sqb.2013.78.023283. [PubMed]
103. Benard EL, van der Sar AM, Ellett F, Lieschke GJ, Spaink HP, Meijer AH. 2012. Infection of zebrafish embryos with intracellular bacterial pathogens. J Vis Exp 2012(61) :3781 http://dx.doi.org/10.3791/3781.
104. Spanjaard B, Junker JP. 2017. Methods for lineage tracing on the organism-wide level. Curr Opin Cell Biol 49:16–21 http://dx.doi.org/10.1016/j.ceb.2017.11.004. [PubMed]
105. Gunster RA, Matthews SA, Holden DW, Thurston TL. 2017. SseK1 and SseK3 type III secretion system effectors inhibit NF-κB signaling and necroptotic cell death in Salmonella-infected macrophages. Infect Immun 85:e00010-17.
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.BAI-0009-2019
2019-04-05
2019-06-18

Abstract:

Systemic infections are a major cause of mortality worldwide and are becoming increasingly untreatable. Recent single-cell data from a mouse model of typhoid fever show that the host immune system actually eradicates many cells, while other organisms thrive at the same time in the same tissue, causing lethal disease progression. The surviving cells have highly heterogeneous metabolism, growth rates, and exposure to various stresses. Emerging evidence suggests that similarly heterogeneous host-pathogen encounters might be a key feature of many infectious diseases. This heterogeneity offers fascinating opportunities for research and application. If we understand the mechanisms that determine the disparate local outcomes, we might be able to develop entirely novel strategies for infection control by broadening successful host antimicrobial attacks and closing permissive niches in which pathogens can thrive. This review describes suitable technologies, a current working model of heterogeneous host- interactions, the impact of diverse subsets on antimicrobial chemotherapy, and major open questions and challenges.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

A paradigm shift in pathogen analysis in host tissues. () Common methods relied on population-level readouts that revealed average properties. This revealed many exciting insights, including identification of important vaccine antigens and antimicrobial targets. () Single-cell technologies reveal an additional striking heterogeneity of pathogen properties and fates that range from vigorous growth to efficient killing. All these diverse host-pathogen encounters can occur in the same host tissue at the same time. Overall disease outcome is the net result of this underlying complexity. Identifying the molecular mechanisms that distinguish successful (for the host) from failing encounters could provide a basis for entirely novel strategies in infection control, by broadening successful host antimicrobial attacks and closing permissive niches in which pathogen subsets can thrive.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0009-2019
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Working model for -host interactions in an infected spleen. () interactions with various phagocyte types. proliferates in macrophages (MΦ) and spreads to other cells. When entering a macrophage, a cell is exposed to a short and sublethal oxidative burst. Infiltrating NK and T cells secrete IFN-γ, which activates some macrophages, enabling them to kill intracellular salmonellae in part through guanylate-binding protein 2 (GBP2). Infection foci also attract inflammatory monocytes (iMO) and polymorphonuclear neutrophils (PMN), which kill intracellular with hypochlorite (HOCl; bleach). Inflammatory monocytes generate and release large amounts of NO, which diffuses to regional salmonellae, which in turn upregulate detoxifying and damage repair enzymes. () Lesion formation and spreading in infected tissues. Growing infection foci attract inflammatory monocytes (blue) and neutrophils (magenta) that kill many . However, some salmonellae escape in infected macrophages (cyan) and start new infection foci elsewhere. Early infection foci are detected by NK and T cells (green), which secrete IFN-γ and activate some of the local macrophages. Other macrophages move to yet other tissue regions, thereby spreading the infection and driving disease progression.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0009-2019
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error