1887

Abstract

Bacteria can evade cohabiting phages through mutations in phage receptors, but these mutations may come at a cost if they disrupt the receptor’s native cellular function. To investigate the relationship between these two conflicting activities, we generated sequence–function maps of LamB with respect to sensitivity to phage and transport of maltodextrin. By comparing 413 missense mutations whose effect on both traits could be analysed, we find that these two phenotypes were correlated, implying that most mutations affect these phenotypes through a common mechanism such as loss of protein stability. However, individual mutations could be found that specifically disrupt -sensitivity without affecting maltodextrin transport. We identify and individually assay nine such mutations, whose spatial positions implicate loop L6 of LamB in binding. Although missense mutations that lead to -resistance are rare, they were approximately as likely to be maltodextrin-utilizing (Mal) as not (Mal), implying that can adapt to while conserving the receptor’s native function. We propose that in order for and to stably cohabitate, selection for -resistance and maltose transport must be spatially or temporally separated.

Funding
This study was supported by the:
  • National Human Genome Research Institute (Award HG000035)
    • Principle Award Recipient: Bryan Andrews
  • National Institute of General Medical Sciences (Award GM103533)
    • Principle Award Recipient: Stanley Fields
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000364
2020-04-02
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/mgen/6/4/mgen000364.html?itemId=/content/journal/mgen/10.1099/mgen.0.000364&mimeType=html&fmt=ahah

References

  1. Gurnev PA, Oppenheim AB, Winterhalter M, Bezrukov SM. Docking of a single phage lambda to its membrane receptor maltoporin as a time-resolved event. J Mol Biol 2006; 359:1447–1455 [View Article][PubMed]
    [Google Scholar]
  2. Bertozzi Silva J, Storms Z, Sauvageau D. Host receptors for bacteriophage adsorption. FEMS Microbiol Lett 2016; 363:1–11 [View Article][PubMed]
    [Google Scholar]
  3. Shoval O, Sheftel H, Shinar G, Hart Y, Ramote O et al. Evolutionary trade-offs, Pareto optimality. Geometry of Phenotype Space 1998; 2012:1–5
    [Google Scholar]
  4. Hottes AK, Freddolino PL, Khare A, Donnell ZN, Liu JC et al. Bacterial adaptation through loss of function. PLoS Genet 2013; 9:e1003617 [View Article][PubMed]
    [Google Scholar]
  5. Berkane E, Orlik F, Stegmeier JF, Charbit A, Winterhalter M et al. Interaction of bacteriophage lambda with its cell surface receptor: an in vitro study of binding of the viral tail protein gpJ to lamb (maltoporin). Biochemistry 2006; 45:2708–2720 [View Article][PubMed]
    [Google Scholar]
  6. Hendrix RW, Casjens S. Bacteriophage λ and its Genetic Neighborhood. In Calendar Richard. editor The Bacteriophages, 2nd ed. Oxford University Press; 2006 pp 409–447
    [Google Scholar]
  7. Szmelcman S, Schwartz M, Silhavy TJ, Boos W. Maltose transport in Escherichia coli K12. A comparison of transport kinetics in wild-type and lambda-resistant mutants as measured by fluorescence quenching. Eur J Biochem 1976; 65:13–19 [View Article][PubMed]
    [Google Scholar]
  8. Lederberg E. Pleiotropy for maltose fermentation and phage resistance in Escherichia coli K-12. Genetics 1955; 40:580–581
    [Google Scholar]
  9. Thirion JP, Hofnung M. On some genetic aspects of phage λ resistance. Genetics 1972; 71:207–216
    [Google Scholar]
  10. Charbit A, Gehring K, Nikaido H, Ferenci T, Hofnung M. Maltose transport and starch binding in phage-resistant point mutants of maltoporin. functional and topological implications. J Mol Biol 1988; 201:487–496 [View Article][PubMed]
    [Google Scholar]
  11. Heine HG, Francis G, Lee KS, Ferenci T. Genetic analysis of sequences in maltoporin that contribute to binding domains and pore structure. J Bacteriol 1988; 170:1730–1738 [View Article][PubMed]
    [Google Scholar]
  12. Schirmer T, Keller TA, Wang YF, Rosenbusch JP. Structural basis for sugar translocation through maltoporin channels at 3.1 A resolution. Science 1995; 267:512–514 [View Article][PubMed]
    [Google Scholar]
  13. Benz R, Schmid A, Vos-Scheperkeuter GH. Mechanism of sugar transport through the sugar-specific lamb channel of Escherichia coli outer membrane. J Membr Biol 1987; 100:21–29 [View Article][PubMed]
    [Google Scholar]
  14. Zheng Y, Roberts RJ, Kasif S. Identification of genes with fast-evolving regions in microbial genomes. Nucleic Acids Res 2004; 32:6347–6357 [View Article][PubMed]
    [Google Scholar]
  15. Araya CL, Fowler DM, Chen W, Muniez I, Kelly JW et al. A fundamental protein property, thermodynamic stability, revealed solely from large-scale measurements of protein function. Proc Natl Acad Sci U S A 2012; 109:16858–16863 [View Article][PubMed]
    [Google Scholar]
  16. Thomason L, Court D, Bubunenko M, Constantino N, Wilson H et al. Recombineering : Genetic Engineering in Bacteria Using Homologous Recombination. Curr Protoc Mol Biol 2007; 1.16:1–24
    [Google Scholar]
  17. Gibson DG, Young L, Chuang R-Y, Venter JC, Hutchison CA et al. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 2009; 6:343–345 [View Article][PubMed]
    [Google Scholar]
  18. Fowler DM, Fields S. Deep mutational scanning: a new style of protein science. Nat Methods 2014; 11:801–807 [View Article][PubMed]
    [Google Scholar]
  19. Doud MB, Bloom JD. Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin. Viruses 2016; 8:155 [View Article][PubMed]
    [Google Scholar]
  20. Weile J, Sun S, Cote AG, Knapp J, Verby M et al. A framework for exhaustively mapping functional missense variants. Mol Syst Biol 2017; 13:957 [View Article][PubMed]
    [Google Scholar]
  21. Zhang XC, Han L. How does a β-barrel integral membrane protein insert into the membrane?. Protein Cell 2016; 7:471–477 [View Article][PubMed]
    [Google Scholar]
  22. Baldwin V, Bhatia M, Luckey M. Folding studies of purified lamb protein, the maltoporin from the Escherichia coli outer membrane: trimer dissociation can be separated from unfolding. Biochim Biophys Acta 2011; 1808:2206–2213 [View Article][PubMed]
    [Google Scholar]
  23. Gehring K, Charbit A, Brissaud E, Hofnung M. Bacteriophage lambda receptor site on the Escherichia coli K-12 lamb protein. J Bacteriol 1987; 169:2103–2106 [View Article][PubMed]
    [Google Scholar]
  24. Bloom JD, Labthavikul ST, Otey CR, Arnold FH. Protein stability promotes evolvability. Proc Natl Acad Sci U S A 2006; 103:5869–5874 [View Article][PubMed]
    [Google Scholar]
  25. Dennehy JJ. What can phages tell us about host-pathogen coevolution?. Int J Evol Biol 2012; 2012:1–12 [View Article][PubMed]
    [Google Scholar]
  26. Koskella B, Brockhurst MA. Bacteria-Phage coevolution as a driver of ecological and evolutionary processes in microbial communities. FEMS Microbiol Rev 2014; 38:916–931 [View Article][PubMed]
    [Google Scholar]
  27. Lenski RE. Coevolution of bacteria and phage: are there endless cycles of bacterial defenses and phage counterdefenses?. J Theor Biol 1984; 108:319–325 [View Article][PubMed]
    [Google Scholar]
  28. Shaw JE, Bingham H, Fuerst CR, Pearson ML. The multisite character of host-range mutations in bacteriophage lambda. Virology 1977; 83:180–194 [View Article][PubMed]
    [Google Scholar]
  29. Weitz JS, Hartman H, Levin SA. Coevolutionary arms races between bacteria and bacteriophage. Proc Natl Acad Sci U S A 2005; 102:9535–9540 [View Article][PubMed]
    [Google Scholar]
  30. Werts C, Michel V, Hofnung M, Charbit A. Adsorption of bacteriophage lambda on the lamb protein of Escherichia coli K-12: point mutations in gene J of lambda responsible for extended host range. J Bacteriol 1994; 176:941–947 [View Article][PubMed]
    [Google Scholar]
  31. Lenski RE, Levin BR. Constraints on the coevolution of bacteria and virulent phage: a model, some experiments, and predictions for natural communities. Am Nat 1985; 125:585–602 [View Article]
    [Google Scholar]
  32. Schrag SJ, Mittler JE. Host-Parasite coexistence: the role of spatial refuges in stabilizing bacteria-phage interactions. Am Nat 1996; 148:348–377 [View Article]
    [Google Scholar]
  33. Gómez P, Buckling A. Bacteria-Phage antagonistic coevolution in soil. Science 2011; 332:106–109 [View Article][PubMed]
    [Google Scholar]
  34. Hall AR, Scanlan PD, Morgan AD, Buckling A. Host – parasite coevolutionary arms races give way to fluctuating selection. Ecol Lett 2011; 14:635–642 [View Article][PubMed]
    [Google Scholar]
  35. Hochberg ME, Baalen M, Van BM. Antagonistic coevolution over productivity gradients. Am Nat 1998; 152:620–634 [View Article][PubMed]
    [Google Scholar]
  36. Lopez-Pascua LdC, Buckling A. Increasing productivity accelerates host – parasite coevolution. J Evol Biol 2008; 21:853–860 [View Article][PubMed]
    [Google Scholar]
  37. Boots M. The evolution of resistance to a parasite is determined by resources. Am Nat 2011; 178:214–220 [View Article][PubMed]
    [Google Scholar]
  38. Lopez Pascua L, Hall AR, Best A, Morgan AD, Boots M et al. Higher resources decrease fluctuating selection during host-parasite coevolution. Ecol Lett 2014; 17:1380–1388 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000364
Loading
/content/journal/mgen/10.1099/mgen.0.000364
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error