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Mutations of the Bacillus subtilis YidC1 (SpoIIIJ) insertase alleviate stress associated with σM-dependent membrane protein overproduction


Autoři: Heng Zhao aff001;  Ankita J. Sachla aff001;  John D. Helmann aff001
Působiště autorů: Department of Microbiology, Cornell University, Ithaca, NY, United States of America aff001
Vyšlo v časopise: Mutations of the Bacillus subtilis YidC1 (SpoIIIJ) insertase alleviate stress associated with σM-dependent membrane protein overproduction. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008263
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008263

Souhrn

In Bacillus subtilis, the extracytoplasmic function σ factor σM regulates cell wall synthesis and is critical for intrinsic resistance to cell wall targeting antibiotics. The anti-σ factors YhdL and YhdK form a complex that restricts the basal activity of σM, and the absence of YhdL leads to runaway expression of the σM regulon and cell death. Here, we report that this lethality can be suppressed by gain-of-function mutations in yidC1 (spoIIIJ), which encodes the major YidC membrane protein insertase in B. subtilis. B. subtilis PY79 YidC1 (SpoIIIJ) contains a single amino acid substitution in a functionally important hydrophilic groove (Q140K), and this allele suppresses the lethality of high σM. Analysis of a library of YidC1 variants reveals that increased charge (+2 or +3) in the hydrophilic groove can compensate for high expression of the σM regulon. Derepression of the σM regulon induces secretion stress, oxidative stress and DNA damage responses, all of which can be alleviated by the YidC1Q140K substitution. We further show that the fitness defect caused by high σM activity is exacerbated in the absence of the SecDF protein translocase or σM-dependent induction of the Spx oxidative stress regulon. Conversely, cell growth is improved by mutation of specific σM-dependent promoters controlling operons encoding integral membrane proteins. Collectively, these results reveal how the σM regulon has evolved to up-regulate membrane-localized complexes involved in cell wall synthesis, and to simultaneously counter the resulting stresses imposed by regulon induction.

Klíčová slova:

Bacillus subtilis – Hyperexpression techniques – Insertion mutation – Integral membrane proteins – Membrane proteins – Point mutation – Polymerase chain reaction – Regulons


Zdroje

1. Helmann JD. Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope. Curr Opin Microbiol. 2016;30:122–32. Epub 2016/02/24. doi: 10.1016/j.mib.2016.02.002 26901131; PubMed Central PMCID: PMC4821709.

2. Sineva E, Savkina M, Ades SE. Themes and variations in gene regulation by extracytoplasmic function (ECF) sigma factors. Curr Opin Microbiol. 2017;36:128–37. doi: 10.1016/j.mib.2017.05.004 28575802; PubMed Central PMCID: PMC5534382.

3. Eiamphungporn W, Helmann JD. The Bacillus subtilis σM regulon and its contribution to cell envelope stress responses. Mol Microbiol. 2008;67(4):830–48. Epub 2008/01/09. doi: 10.1111/j.1365-2958.2007.06090.x 18179421; PubMed Central PMCID: PMC3025603.

4. Horsburgh MJ, Moir A. σM, an ECF RNA polymerase sigma factor of Bacillus subtilis 168, is essential for growth and survival in high concentrations of salt. Mol Microbiol. 1999;32(1):41–50. Epub 1999/04/27. doi: 10.1046/j.1365-2958.1999.01323.x 10216858.

5. Luo Y, Helmann JD. Analysis of the role of Bacillus subtilis σM in beta-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis. Mol Microbiol. 2012;83(3):623–39. Epub 2012/01/04. doi: 10.1111/j.1365-2958.2011.07953.x 22211522; PubMed Central PMCID: PMC3306796.

6. Meeske AJ, Riley EP, Robins WP, Uehara T, Mekalanos JJ, Kahne D, et al. SEDS proteins are a widespread family of bacterial cell wall polymerases. Nature. 2016;537(7622):634–8. Epub 2016/08/16. doi: 10.1038/nature19331 27525505; PubMed Central PMCID: PMC5161649.

7. Asai K. Anti-sigma factor-mediated cell surface stress responses in Bacillus subtilis. Genes Genet Syst. 2018;92(5):223–34. Epub 2018/01/19. doi: 10.1266/ggs.17-00046 29343670.

8. Woods EC, McBride SM. Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors. Microbes Infect. 2017;19(4–5):238–48. doi: 10.1016/j.micinf.2017.01.007 28153747; PubMed Central PMCID: PMC5403605.

9. Yoshimura M, Asai K, Sadaie Y, Yoshikawa H. Interaction of Bacillus subtilis extracytoplasmic function (ECF) sigma factors with the N-terminal regions of their potential anti-sigma factors. Microbiology. 2004;150(Pt 3):591–9. doi: 10.1099/mic.0.26712-0 14993308

10. Zhao H, Roistacher DM, Helmann JD. Deciphering the essentiality and function of the anti-σM factors in Bacillus subtilis. Mol Microbiol. 2019. doi: 10.1111/mmi.14216 30715747.

11. Murakami T, Haga K, Takeuchi M, Sato T. Analysis of the Bacillus subtilis spoIIIJ gene and its paralogue gene, yqjG. J Bacteriol. 2002;184(7):1998–2004. doi: 10.1128/JB.184.7.1998-2004.2002 11889108; PubMed Central PMCID: PMC134917.

12. Tjalsma H, Bron S, van Dijl JM. Complementary impact of paralogous Oxa1-like proteins of Bacillus subtilis on post-translocational stages in protein secretion. J Biol Chem. 2003;278(18):15622–32. doi: 10.1074/jbc.M301205200 12586834.

13. Zeigler DR, Pragai Z, Rodriguez S, Chevreux B, Muffler A, Albert T, et al. The origins of 168, W23, and other Bacillus subtilis legacy strains. J Bacteriol. 2008;190(21):6983–95. Epub 2008/08/30. doi: 10.1128/JB.00722-08 18723616; PubMed Central PMCID: PMC2580678.

14. Schroeder JW, Simmons LA. Complete Genome Sequence of Bacillus subtilis Strain PY79. Genome Announc. 2013;1(6). Epub 2013/12/21. doi: 10.1128/genomeA.01085-13 24356846; PubMed Central PMCID: PMC3868870.

15. Dubnau D, Cirigliano C. Fate of transforming DNA following uptake by competent Bacillus subtilis. Formation and properties of products isolated from transformed cells which are derived entirely from donor DNA. J Mol Biol. 1972;64(1):9–29. Epub 1972/02/28. doi: 10.1016/0022-2836(72)90318-x 4622632.

16. Kumazaki K, Chiba S, Takemoto M, Furukawa A, Nishiyama K, Sugano Y, et al. Structural basis of Sec-independent membrane protein insertion by YidC. Nature. 2014;509(7501):516–20. Epub 2014/04/18. doi: 10.1038/nature13167 24739968.

17. Tsirigotaki A, De Geyter J, Sostaric N, Economou A, Karamanou S. Protein export through the bacterial Sec pathway. Nat Rev Microbiol. 2017;15(1):21–36. Epub 2016/11/29. doi: 10.1038/nrmicro.2016.161 27890920.

18. Hennon SW, Soman R, Zhu L, Dalbey RE. YidC/Alb3/Oxa1 Family of Insertases. J Biol Chem. 2015;290(24):14866–74. Epub 2015/05/08. doi: 10.1074/jbc.R115.638171 25947384; PubMed Central PMCID: PMC4463434.

19. Saller MJ, Fusetti F, Driessen AJ. Bacillus subtilis SpoIIIJ and YqjG function in membrane protein biogenesis. J Bacteriol. 2009;191(21):6749–57. Epub 2009/09/01. doi: 10.1128/JB.00853-09 19717609; PubMed Central PMCID: PMC2795313.

20. Errington J, Appleby L, Daniel RA, Goodfellow H, Partridge SR, Yudkin MD. Structure and function of the spoIIIJ gene of Bacillus subtilis: a vegetatively expressed gene that is essential for sigma G activity at an intermediate stage of sporulation. J Gen Microbiol. 1992;138(12):2609–18. Epub 1992/12/01. doi: 10.1099/00221287-138-12-2609 1487728.

21. Chiba S, Ito K. MifM monitors total YidC activities of Bacillus subtilis, including that of YidC2, the target of regulation. J Bacteriol. 2015;197(1):99–107. Epub 2014/10/15. doi: 10.1128/JB.02074-14 25313395; PubMed Central PMCID: PMC4288694.

22. Corte L, Valente F, Serrano M, Gomes CM, Moran CP Jr., Henriques AO. A conserved cysteine residue of Bacillus subtilis SpoIIIJ is important for endospore development. PLoS One. 2014;9(8):e99811. Epub 2014/08/19. doi: 10.1371/journal.pone.0099811 25133632; PubMed Central PMCID: PMC4136701.

23. Saller MJ, Otto A, Berrelkamp-Lahpor GA, Becher D, Hecker M, Driessen AJ. Bacillus subtilis YqjG is required for genetic competence development. Proteomics. 2011;11(2):270–82. Epub 2011/01/05. doi: 10.1002/pmic.201000435 21204254.

24. Quisel JD, Burkholder WF, Grossman AD. In vivo effects of sporulation kinases on mutant Spo0A proteins in Bacillus subtilis. J Bacteriol. 2001;183(22):6573–8. doi: 10.1128/JB.183.22.6573-6578.2001 11673427; PubMed Central PMCID: PMC95488.

25. Shimokawa-Chiba N, Kumazaki K, Tsukazaki T, Nureki O, Ito K, Chiba S. Hydrophilic microenvironment required for the channel-independent insertase function of YidC protein. Proc Natl Acad Sci U S A. 2015;112(16):5063–8. Epub 2015/04/10. doi: 10.1073/pnas.1423817112 25855636; PubMed Central PMCID: PMC4413333.

26. Chiba S, Ito K. Multisite ribosomal stalling: a unique mode of regulatory nascent chain action revealed for MifM. Mol Cell. 2012;47(6):863–72. Epub 2012/08/07. doi: 10.1016/j.molcel.2012.06.034 22864117.

27. Kuhn A, Kiefer D. Membrane protein insertase YidC in bacteria and archaea. Mol Microbiol. 2017;103(4):590–4. Epub 2016/11/24. doi: 10.1111/mmi.13586 27879020.

28. Hyyrylainen HL, Bolhuis A, Darmon E, Muukkonen L, Koski P, Vitikainen M, et al. A novel two-component regulatory system in Bacillus subtilis for the survival of severe secretion stress. Mol Microbiol. 2001;41(5):1159–72. doi: 10.1046/j.1365-2958.2001.02576.x 11555295.

29. Darmon E, Noone D, Masson A, Bron S, Kuipers OP, Devine KM, et al. A novel class of heat and secretion stress-responsive genes is controlled by the autoregulated CssRS two-component system of Bacillus subtilis. J Bacteriol. 2002;184(20):5661–71. Epub 2002/09/25. doi: 10.1128/JB.184.20.5661-5671.2002 12270824; PubMed Central PMCID: PMC139597.

30. Podgornaia AI, Laub MT. Determinants of specificity in two-component signal transduction. Curr Opin Microbiol. 2013;16(2):156–62. Epub 2013/01/29. doi: 10.1016/j.mib.2013.01.004 23352354.

31. Takahashi N, Gruber CC, Yang JH, Liu X, Braff D, Yashaswini CN, et al. Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality. Proc Natl Acad Sci U S A. 2017. Epub 2017/08/11. doi: 10.1073/pnas.1707466114 28794281; PubMed Central PMCID: PMC5576823.

32. Kohanski MA, Dwyer DJ, Wierzbowski J, Cottarel G, Collins JJ. Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death. Cell. 2008;135(4):679–90. Epub 2008/11/18. doi: 10.1016/j.cell.2008.09.038 19013277; PubMed Central PMCID: PMC2684502.

33. Zhu B, Stulke J. SubtiWiki in 2018: from genes and proteins to functional network annotation of the model organism Bacillus subtilis. Nucleic Acids Res. 2018;46(D1):D743–D8. Epub 2018/05/23. doi: 10.1093/nar/gkx908 29788229; PubMed Central PMCID: PMC5753275.

34. Price CE, Driessen AJ. YidC is involved in the biogenesis of anaerobic respiratory complexes in the inner membrane of Escherichia coli. J Biol Chem. 2008;283(40):26921–7. doi: 10.1074/jbc.M804490200 18635537.

35. Dalbey RE, Kuhn A, Zhu L, Kiefer D. The membrane insertase YidC. Biochim Biophys Acta. 2014;1843(8):1489–96. doi: 10.1016/j.bbamcr.2013.12.022 24418623.

36. Chiba S, Lamsa A, Pogliano K. A ribosome-nascent chain sensor of membrane protein biogenesis in Bacillus subtilis. EMBO J. 2009;28(22):3461–75. Epub 2009/09/26. doi: 10.1038/emboj.2009.280 19779460; PubMed Central PMCID: PMC2782093.

37. Chen Y, Soman R, Shanmugam SK, Kuhn A, Dalbey RE. The role of the strictly conserved positively charged residue differs among the Gram-positive, Gram-negative, and chloroplast YidC homologs. J Biol Chem. 2014;289(51):35656–67. Epub 2014/11/02. doi: 10.1074/jbc.M114.595082 25359772; PubMed Central PMCID: PMC4271247.

38. Mishra S, Crowley PJ, Wright KR, Palmer SR, Walker AR, Datta S, et al. Membrane proteomic analysis reveals overlapping and independent functions of Streptococcus mutans Ffh, YidC1, and YidC2. Mol Oral Microbiol. 2019;34(4):131–52. doi: 10.1111/omi.12261 31034136; PubMed Central PMCID: PMC6625898.

39. Luo Y, Asai K, Sadaie Y, Helmann JD. Transcriptomic and phenotypic characterization of a Bacillus subtilis strain without extracytoplasmic function sigma factors. J Bacteriol. 2010;192(21):5736–45. Epub 2010/09/08. doi: 10.1128/JB.00826-10 20817771; PubMed Central PMCID: PMC2953670.

40. Zhao H, Sun Y, Peters JM, Gross CA, Garner EC, Helmann JD. Depletion of Undecaprenyl Pyrophosphate Phosphatases Disrupts Cell Envelope Biogenesis in Bacillus subtilis. J Bacteriol. 2016;198(21):2925–35. doi: 10.1128/JB.00507-16 27528508; PubMed Central PMCID: PMC5055597.

41. Hartl B, Wehrl W, Wiegert T, Homuth G, Schumann W. Development of a new integration site within the Bacillus subtilis chromosome and construction of compatible expression cassettes. J Bacteriol. 2001;183(8):2696–9. Epub 2001/03/29. doi: 10.1128/JB.183.8.2696-2699.2001 11274134; PubMed Central PMCID: PMC95191.

42. Koo BM, Kritikos G, Farelli JD, Todor H, Tong K, Kimsey H, et al. Construction and Analysis of Two Genome-Scale Deletion Libraries for Bacillus subtilis. Cell Syst. 2017;4(3):291–305 e7. Epub 2017/02/13. doi: 10.1016/j.cels.2016.12.013 28189581; PubMed Central PMCID: PMC5400513.

43. Rojas-Tapias DF, Helmann JD. Induction of the Spx regulon by cell wall stress reveals novel regulatory mechanisms in Bacillus subtilis. Mol Microbiol. 2018;107(5):659–74. Epub 2017/12/23. doi: 10.1111/mmi.13906 29271514; PubMed Central PMCID: PMC5820111.

44. Altenbuchner J. Editing of the Bacillus subtilis Genome by the CRISPR-Cas9 System. Appl Environ Microbiol. 2016;82(17):5421–7. Epub 2016/06/28. doi: 10.1128/AEM.01453-16 27342565; PubMed Central PMCID: PMC4988203.

45. Moszer I, Rocha EP, Danchin A. Codon usage and lateral gene transfer in Bacillus subtilis. Curr Opin Microbiol. 1999;2(5):524–8. Epub 1999/10/06. 10508724.

46. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82. Epub 2012/06/30. doi: 10.1038/nmeth.2019 22743772; PubMed Central PMCID: PMC3855844.

47. Zhao H, Roistacher DM, Helmann JD. Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis. Mol Microbiol. 2018;109(6):826–44. Epub 2018/07/12. doi: 10.1111/mmi.14078 29995990; PubMed Central PMCID: PMC6185803.

48. Radeck J, Kraft K, Bartels J, Cikovic T, Durr F, Emenegger J, et al. The Bacillus BioBrick Box: generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis. J Biol Eng. 2013;7(1):29. Epub 2013/12/04. doi: 10.1186/1754-1611-7-29 24295448; PubMed Central PMCID: PMC4177231.

49. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12. Epub 2004/07/21. doi: 10.1002/jcc.20084 15264254.

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