Unisexual reproduction promotes competition for mating partners in the global human fungal pathogen Cryptococcus deneoformans

English version

Autoři: Ci Fu ^aff001; Torin P. Thielhelm ^aff001; Joseph Heitman ^aff001
Působiště autorů: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America ^aff001
Vyšlo v časopise: Unisexual reproduction promotes competition for mating partners in the global human fungal pathogen Cryptococcus deneoformans. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008394
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008394

Souhrn

Courtship is pivotal for successful mating. However, courtship is challenging for the Cryptococcus neoformans species complex, comprised of opportunistic fungal pathogens, as the majority of isolates are α mating type. In the absence of mating partners of the opposite mating type, C. deneoformans can undergo unisexual reproduction, during which a yeast-to-hyphal morphological transition occurs. Hyphal growth during unisexual reproduction is a quantitative trait, which reflects a strain’s ability to undergo unisexual reproduction. In this study, we determined whether unisexual reproduction confers an ecological benefit by promoting foraging for mating partners. Through competitive mating assays using strains with different abilities to produce hyphae, we showed that unisexual reproduction potential did not enhance competition for mating partners of the same mating type, but when cells of the opposite mating type were present, cells with enhanced hyphal growth were more competitive for mating partners of either the same or opposite mating type. Enhanced mating competition was also observed in a strain with increased hyphal production that lacks the mating repressor gene GPA3, which contributes to the pheromone response. Hyphal growth in unisexual strains also enables contact between adjacent colonies and enhances mating efficiency during mating confrontation assays. The pheromone response pathway activation positively correlated with unisexual reproduction hyphal growth during bisexual mating and exogenous pheromone promoted bisexual cell fusion. Despite the benefit in competing for mating partners, unisexual reproduction conferred a fitness cost. Taken together, these findings suggest C. deneoformans employs hyphal growth to facilitate contact between colonies at long distances and utilizes pheromone sensing to enhance mating competition.

Klíčová slova:

Biology and life sciences – Cell biology – Cell physiology – Cell fusion – Biochemistry – Pheromones – Psychology – Behavior – Animal behavior – Foraging – Zoology – Organisms – Eukaryota – Fungi – Yeast – Saccharomyces – Saccharomyces cerevisiae – Candida – Candida albicans – Cryptococcus – Cryptococcus neoformans – Microbiology – Medical microbiology – Microbial pathogens – Fungal pathogens – Mycology – Genetics – Gene expression – Social sciences – Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Yeast and fungal models – Medicine and health sciences – Pathology and laboratory medicine – Pathogens

Zdroje

1. Muller M.N., and Wrangham R.W. (2009). Sexual coercion in primates and humans: an evolutionary perspective on male aggression against females, (Cambridge, Mass.: Harvard University Press).

2. Clark C.J., and Mistick E.A. (2018). Strategic acoustic control of a hummingbird courtship dive. Curr Biol 28, 1257–1264. doi: 10.1016/j.cub.2018.03.021 29657113

3. Clemens J., Coen P., Roemschied F.A., Pereira T.D., Mazumder D., Aldarondo D.E., Pacheco D.A., and Murthy M. (2018). Discovery of a new song mode in Drosophila reveals hidden structure in the sensory and neural drivers of behavior. Curr Biol 28, 2400–2412 e2406. doi: 10.1016/j.cub.2018.06.011 30057309

4. Lardner B., and bin Lakim M. (2002). Animal communication: tree-hole frogs exploit resonance effects. Nature 420, 475. doi: 10.1038/420475a 12466831

5. Berglund A., and Rosenqvist G. (2001). Male pipefish prefer ornamented females. Anim Behav 61, 345–350.

6. Ydenberg C.A., and Rose M.D. (2008). Yeast mating: a model system for studying cell and nuclear fusion. Methods Mol. Biol. 475, 3–20. doi: 10.1007/978-1-59745-250-2_1 18979235

7. Dyer P.S., Ingram D.S., and Johnstone K. (1992). The control of sexual morphogenesis in the ascomycotina. Biol Rev 67, 421–458.

8. Miller M.G., and Johnson A.D. (2002). White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110, 293–302. doi: 10.1016/s0092-8674(02)00837-1 12176317

9. Jones S.K. Jr., and Bennett R.J. (2011). Fungal mating pheromones: choreographing the dating game. Fungal Genet. Biol. 48, 668–676. doi: 10.1016/j.fgb.2011.04.001 21496492

10. Jackson C.L., and Hartwell L.H. (1990). Courtship in Saccharomyces cerevisiae: an early cell-cell interaction during mating. Mol. Cell Biol. 10, 2202–2213. doi: 10.1128/mcb.10.5.2202 2183023

11. Jackson C.L., and Hartwell L.H. (1990). Courtship in S. cerevisiae: both cell types choose mating partners by responding to the strongest pheromone signal. Cell 63, 1039–1051. doi: 10.1016/0092-8674(90)90507-b 2257622

12. Dudin O., Merlini L., and Martin S.G. (2016). Spatial focalization of pheromone/MAPK signaling triggers commitment to cell-cell fusion. Genes Dev. 30, 2226–2239. doi: 10.1101/gad.286922.116 27798845

13. Merlini L., Khalili B., Bendezu F.O., Hurwitz D., Vincenzetti V., Vavylonis D., and Martin S.G. (2016). Local pheromone release from dynamic polarity sites underlies cell-cell pairing during yeast mating. Curr Biol. 26, 1117–1125. doi: 10.1016/j.cub.2016.02.064 27020743

14. Scaduto C.M., Kabrawala S., Thomson G.J., Scheving W., Ly A., Anderson M.Z., Whiteway M., and Bennett R.J. (2017). Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans. Proc. Natl. Acad. Sci. USA 114, 13780–13785. doi: 10.1073/pnas.1711141115 29255038

15. Kwon-Chung K.J. (1976). Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. Mycologia 68, 821–833. 790172

16. Lin X., Hull C.M., and Heitman J. (2005). Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature 434, 1017–1021. doi: 10.1038/nature03448 15846346

17. Wickes B.L., Mayorga M.E., Edman U., and Edman J.C. (1996). Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the α-mating type. Proc. Natl. Acad. Sci. USA 93, 7327–7331. doi: 10.1073/pnas.93.14.7327 8692992

18. Fu C., Sun S., Billmyre R.B., Roach K.C., and Heitman J. (2015). Unisexual versus bisexual mating in Cryptococcus neoformans: Consequences and biological impacts. Fungal Genet. Biol. 78, 65–75. doi: 10.1016/j.fgb.2014.08.008 25173822

19. Wang L., and Lin X. (2011). Mechanisms of unisexual mating in Cryptococcus neoformans. Fungal Genet. Biol. 48, 651–660. doi: 10.1016/j.fgb.2011.02.001 21320625

20. Gyawali R., Zhao Y., Lin J., Fan Y., Xu X., Upadhyay S., and Lin X. (2017). Pheromone independent unisexual development in Cryptococcus neoformans. PLoS Genet. 13, e1006772. doi: 10.1371/journal.pgen.1006772 28467481

21. Xu X., Lin J., Zhao Y., Kirkman E., So Y.S., Bahn Y.S., and Lin X. (2017). Glucosamine stimulates pheromone-independent dimorphic transition in Cryptococcus neoformans by promoting Crz1 nuclear translocation. PLoS Genet 13, e1006982. doi: 10.1371/journal.pgen.1006982 28898238

22. Tian X., He G.-J., Hu P., Chen L., Tao C., Cui Y.-L., Shen L., Ke W., Xu H., Zhao Y., et al. (2018). Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide. Nat. Microbiol. 3, 698–707. doi: 10.1038/s41564-018-0160-4 29784977

23. Fu C., and Heitman J. (2017). PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct bisexual and unisexual cycles in the Cryptococcus pathogenic species complex. PLoS Genet. 13, e1007113. doi: 10.1371/journal.pgen.1007113 29176784

24. Fu C., Donadio N., Cardenas M.E., and Heitman J. (2018). Dissecting the roles of the calcineurin pathway in unisexual reproduction, stress responses, and virulence in Cryptococcus deneoformans. Genetics 208, 639–653. doi: 10.1534/genetics.117.300422 29233811

25. Kwon-Chung K.J., and Bennett J.E. (1978). Distribution of α and a mating types of Cryptococcus neoformans among natural and clinical isolates. Am. J. Epidemiol 108, 337–340. doi: 10.1093/oxfordjournals.aje.a112628 364979

26. Litvintseva A.P., Kestenbaum L., Vilgalys R., and Mitchell T.G. (2005). Comparative analysis of environmental and clinical populations of Cryptococcus neoformans. J. Clin. Microbiol. 43, 556–564. doi: 10.1128/JCM.43.2.556-564.2005 15695645

27. Cogliati M., D'Amicis R., Zani A., Montagna M.T., Caggiano G., De Giglio O., Balbino S., De Donno A., Serio F., Susever S., et al. (2016). Environmental distribution of Cryptococcus neoformans and C. gattii around the Mediterranean basin. FEMS Yeast Res 16.

28. Roach K.C., and Heitman J. (2014). Unisexual reproduction reverses Muller's ratchet. Genetics 198, 1059–1069. doi: 10.1534/genetics.114.170472 25217049

29. Ni M., Feretzaki M., Li W., Floyd-Averette A., Mieczkowski P., Dietrich F.S., and Heitman J. (2013). Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans. PLoS Biol. 11, e1001653. doi: 10.1371/journal.pbio.1001653 24058295

30. Saul N., Krockenberger M., and Carter D. (2008). Evidence of recombination in mixed-mating-type and alpha-only populations of Cryptococcus gattii sourced from single eucalyptus tree hollows. Eukaryot. Cell 7, 727–734. doi: 10.1128/EC.00020-08 18281600

31. Litvintseva A.P., Marra R.E., Nielsen K., Heitman J., Vilgalys R., and Mitchell T.G. (2003). Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in Sub-Saharan Africa. Eukaryot. Cell 2, 1162–1168. doi: 10.1128/EC.2.6.1162-1168.2003 14665451

32. Campbell L.T., Currie B.J., Krockenberger M., Malik R., Meyer W., Heitman J., and Carter D. (2005). Clonality and recombination in genetically differentiated subgroups of Cryptococcus gattii. Eukaryot. Cell 4, 1403–1409. doi: 10.1128/EC.4.8.1403-1409.2005 16087745

33. Cullen P.J., and Sprague G.F. Jr. (2012). The regulation of filamentous growth in yeast. Genetics 190, 23–49. doi: 10.1534/genetics.111.127456 22219507

34. Phadke S.S., Feretzaki M., and Heitman J. (2013). Unisexual reproduction enhances fungal competitiveness by promoting habitat exploration via hyphal growth and sporulation. Eukaryot. Cell 12, 1155–1159. doi: 10.1128/EC.00147-13 23794511

35. Lin X., Huang J.C., Mitchell T.G., and Heitman J. (2006). Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATα allele enhances filamentation. PLoS Genet. 2, e187. doi: 10.1371/journal.pgen.0020187 17112316

36. Heitman J., Allen B., Alspaugh J.A., and Kwon-Chung K.J. (1999). On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans. Fungal Genet Biol 28, 1–5. doi: 10.1006/fgbi.1999.1155 10512666

37. Kwon-Chung K.J. (1975). A new genus, Filobasidiella, the perfect state of Cryptococcus neoformans. Mycologia 67, 1197–1200. 765816

38. Kwon-Chung K.J., Edman J.C., and Wickes B.L. (1992). Genetic association of mating types and virulence in Cryptococcus neoformans. Infect. Immun. 60, 602–605. 1730495

39. Zhai B., Zhu P., Foyle D., Upadhyay S., Idnurm A., and Lin X. (2013). Congenic strains of the filamentous form of Cryptococcus neoformans for studies of fungal morphogenesis and virulence. Infect. Immun. 81, 2626–2637. doi: 10.1128/IAI.00259-13 23670559

40. Hsueh Y.P., Xue C., and Heitman J. (2007). G protein signaling governing cell fate decisions involves opposing Gα subunits in Cryptococcus neoformans. Mol. Biol. Cell 18, 3237–3249. doi: 10.1091/mbc.E07-02-0133 17581859

41. Gong J., Grodsky J.D., Zhang Z., and Wang P. (2014). A Ric8/synembryn homolog promotes Gpa1 and Gpa2 activation to respectively regulate cyclic AMP and pheromone signaling in Cryptococcus neoformans. Eukaryot Cell 13, 1290–1299. doi: 10.1128/EC.00109-14 25084863

42. Feretzaki M., and Heitman J. (2013). Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans. PLoS Genet. 9, e1003688. doi: 10.1371/journal.pgen.1003688 23966871

43. Nielsen K., Cox G.M., Wang P., Toffaletti D.L., Perfect J.R., and Heitman J. (2003). Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and α isolates. Infect. Immun. 71, 4831–4841. doi: 10.1128/IAI.71.9.4831-4841.2003 12933823

44. Huberman L.B., and Murray A.W. (2013). Genetically engineered transvestites reveal novel mating genes in budding yeast. Genetics 195, 1277–1290. doi: 10.1534/genetics.113.155846 24121774

45. Sprague G.F. Jr., and Herskowitz I. (1981). Control of yeast cell type by the mating type locus. I. Identification and control of expression of the a-specific gene BAR1. J. Mol. Biol. 153, 305–321. doi: 10.1016/0022-2836(81)90280-1 7040681

46. Banderas A., Koltai M., Anders A., and Sourjik V. (2016). Sensory input attenuation allows predictive sexual response in yeast. Nat Commun 7, 12590. doi: 10.1038/ncomms12590 27557894

47. Jin M., Errede B., Behar M., Mather W., Nayak S., Hasty J., Dohlman H.G., and Elston T.C. (2011). Yeast dynamically modify their environment to achieve better mating efficiency. Sci Signal 4.

48. Shen W.C., Davidson R.C., Cox G.M., and Heitman J. (2002). Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot. Cell 1, 366–377. doi: 10.1128/EC.1.3.366-377.2002 12455985

49. Lin X., Jackson J.C., Feretzaki M., Xue C., and Heitman J. (2010). Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite -⁠ and same-sex mating in Cryptococcus neoformans. PLoS Genet. 6, e1000953. doi: 10.1371/journal.pgen.1000953 20485569

50. Erdman S., and Snyder M. (2001). A filamentous growth response mediated by the yeast mating pathway. Genetics 159, 919–928. 11729141

51. Davidson R.C., Moore T.D., Odom A.R., and Heitman J. (2000). Characterization of the MFα pheromone of the human fungal pathogen cryptococcus neoformans. Mol Microbiol 38, 1017–1026. doi: 10.1046/j.1365-2958.2000.02213.x 11123675

52. Lang G.I., Murray A.W., and Botstein D. (2009). The cost of gene expression underlies a fitness trade-off in yeast. Proc. Natl. Acad. Sci. USA 106, 5755–5760. doi: 10.1073/pnas.0901620106 19299502

53. Tscharke R.L., Lazera M., Chang Y.C., Wickes B.L., and Kwon-Chung K.J. (2003). Haploid fruiting in Cryptococcus neoformans is not mating type α-specific. Fungal Genet. Biol. 39, 230–237. 12892636

54. Newby G.A., and Lindquist S. (2017). Pioneer cells established by the [SWI+] prion can promote dispersal and out-crossing in yeast. PLoS Biol 15, e2003476. doi: 10.1371/journal.pbio.2003476 29135981

55. Fraser J.A., Subaran R.L., Nichols C.B., and Heitman J. (2003). Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii: implications for an outbreak on Vancouver Island, Canada. Eukaryot. Cell 2, 1036–1045. doi: 10.1128/EC.2.5.1036-1045.2003 14555486

56. Idnurm A., Reedy J.L., Nussbaum J.C., and Heitman J. (2004). Cryptococcus neoformans virulence gene discovery through insertional mutagenesis. Eukaryot. Cell 3, 420–429. doi: 10.1128/EC.3.2.420-429.2004 15075272

57. Davidson R.C., Cruz M.C., Sia R.A., Allen B., Alspaugh J.A., and Heitman J. (2000). Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans. Fungal Genet. Biol. 29, 38–48. doi: 10.1006/fgbi.1999.1180 10779398

58. Davidson R.C., Blankenship J.R., Kraus P.R., de Jesus Berrios M., Hull C.M., D'Souza C., Wang P., and Heitman J. (2002). A PCR-based strategy to generate integrative targeting alleles with large regions of homology. Microbiology 148, 2607–2615. doi: 10.1099/00221287-148-8-2607 12177355