Disease can act as a driving force in shaping genetic makeup across populations, even species, if the impacts influence a particularly sensitive part of their life cycles. White-nose disease is caused by a fungal pathogen infecting bats during hibernation. The mycosis has caused massive population declines of susceptible species in North America, particularly in the genus Myotis. However, Myotis bats appear to tolerate infection in Eurasia, where the fungal pathogen has co-evolved with its bat hosts for an extended period of time. Therefore, with susceptible and tolerant populations, the fungal disease provides a unique opportunity to tease apart factors contributing to tolerance at a genomic level to and gain an understanding of the evolution of non-harmful in host-parasite interactions. To investigate if the fungal disease has caused adaptation on a genomic level in Eurasian bat species, we adopted both whole-genome sequencing approaches and a literature search to compile a set of 300 genes from which to investigate signals of positive selection in genomes of 11 Eurasian bats at the codon-level. Our results indicate significant positive selection in 38 genes, many of which have a marked role in responses to infection. Our findings suggest that white-nose syndrome may have applied a significant selective pressure on Eurasian Myotis-bats in the past, which can contribute their survival in co-existence with the pathogen. Our findings provide an insight on the selective pressure pathogens afflict on their hosts using methodology that can be adapted to other host-pathogen study systems.

Competence Center for Bat Conservation Saxony Anhalt in the South Harz Karst Landscape Biosphere Reserve Südharz Germany

Department of Biology Bucknell University Lewisburg PA USA

Dept Botany and Zoology Faculty of Science Masaryk University Kotlarska 2 Brno 611 37 Czech Republic

Finnish Museum of Natural History BatLab Finland University of Helsinki Helsinki Finland

German Bat Observatory Berlin Germany

Graduate School of Agricultural and Life Sciences The University of Tokyo Fuji Iyashinomori Woodland Study Center The University of Tokyo Yamanakako Japan

Institute of Biology Karelian Research Centre Russian Academy of Sciences Petrozavodsk Russia

Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK

Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization Northeast Normal University Changchun China

Papanin Institute for Biology of Inland Waters Russian Academy of Sciences Borok Russia

Zoological Institute and Museum University of Greifswald Greifswald Germany

Zobrazit více v PubMed

Cunningham AA, Daszak P, Wood JLN. One health, emerging infectious diseases and wildlife: two decades of progress? Philosophical Trans Royal Soc B: Biol Sci. 2017;372:20160167.10.1098/rstb.2016.0167 PubMed DOI PMC

Baylis M, Risley C. Infectious diseases, climate change effects on. In: Meyers RA, editor. Encyclopedia of sustainability science and technology. New York, NY: Springer; 2012. pp. 5358–78.

Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, et al. Infectious disease in an era of global change. Nat Rev Microbiol. 2022;20:193–205. 10.1038/s41579-021-00639-z PubMed DOI PMC

Daszak P, Cunningham AA, Hyatt AD. Emerging infectious diseases of wildlife-threats to biodiversity and human health. Science. 2000;287:443–9. 10.1126/science.287.5452.443 PubMed DOI

Whiting-Fawcett F, Blomberg AS, Troitsky T, Meierhofer MB, Field KA, Puechmaille SJ et al. A palearctic view of a bat fungal disease. Conserv Biol. 2024;n/an/a:e14265. PubMed

Blehert DS, Hicks AC, Behr M, Meteyer CU, Berlowski-Zier BM, Buckles EL, et al. Bat white-nose syndrome: an emerging fungal pathogen? Science. 2009;323:227–227. 10.1126/science.1163874 PubMed DOI

Frick WF, Puechmaille SJ, Willis CKR. White-nose syndrome in bats. In: Voigt CC, Kingston T, editors. Bats in the Anthropocene: conservation of bats in a changing world. Cham: Springer International Publishing; 2016. pp. 245–62.

Frick WF, Puechmaille SJ, Hoyt JR, Nickel BA, Langwig KE, Foster JT, et al. Disease alters macroecological patterns of north American bats. Glob Ecol Biogeogr. 2015;24:741–9.10.1111/geb.12290 DOI

Puechmaille SJ, Wibbelt G, Korn V, Fuller H, Forget F, Mühldorfer K, et al. Pan-european distribution of white-nose syndrome fungus (Geomyces destructans) not associated with mass mortality. PLoS ONE. 2011;6:e19167. 10.1371/journal.pone.0019167 PubMed DOI PMC

Fritze M, Puechmaille SJ. Identifying unusual mortality events in bats: a baseline for bat hibernation monitoring and white- ­ nose syndrome. Mammal Rev. 2018;48:224–8.10.1111/mam.12122 DOI

Fischer NM, Dool SE, Puechmaille SJ. Seasonal patterns of Pseudogymnoascus destructans germination indicate host – pathogen coevolution. Biol Lett. 2020;16:1–5.10.1098/rsbl.2020.0177 PubMed DOI PMC

Reeder DM, Frank CL, Turner GG, Meteyer CU, Kurta A, Britzke ER et al. Frequent arousal from hibernation linked to severity of infection and mortality in bats with white-nose syndrome. PLoS ONE. 2012;7. PubMed PMC

Warnecke L, Turner JM, Bollinger TK, Lorch JM, Misra V, Cryan PM, et al. Inoculation of bats with European Geomyces destructans supports the novel pathogen hypothesis for the origin of white-nose syndrome. Proc Natl Acad Sci U S A. 2012;109:6999–7003. 10.1073/pnas.1200374109 PubMed DOI PMC

Meteyer CU, Buckles EL, Blehert DS, Hicks AC, Green DE, Shearn-Bochsler V, et al. Histopathologic criteria to confirm white-nose syndrome in bats. J Vet Diagn Invest. 2009;21:411–4. 10.1177/104063870902100401 PubMed DOI

Field KA, Johnson JS, Lilley TM, Reeder SM, Rogers EJ, Behr MJ, et al. The white-nose syndrome transcriptome: activation of anti-fungal host responses in wing tissue of hibernating bats. PLoS Pathog. 2015;11:1–29.10.1371/journal.ppat.1005168 PubMed DOI PMC

Field KA, Sewall BJ, Prokkola JM, Turner GG, Gagnon MF, Lilley TM, et al. Effect of torpor on host transcriptomic responses to a fungal pathogen in hibernating bats. Mol Ecol. 2018;27:3727–43.10.1111/mec.14827 PubMed DOI

Lilley TM, Prokkola JM, Johnson JS, Rogers EJ, Gronsky S, Kurta A, et al. Immune responses in hibernating little brown myotis (Myotis lucifugus) with white-nose syndrome. Proc R Soc B. 2017;284:20162232. 10.1098/rspb.2016.2232 PubMed DOI PMC

Flieger M, Bandouchova H, Cerny J, Chudíčková M, Kolarik M, Kovacova V, et al. Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection. Sci Rep. 2016;6:33200. 10.1038/srep33200 PubMed DOI PMC

McGuire LP, Mayberry HW, Willis CKR. White-nose syndrome increases torpid metabolic rate and evaporative water loss in hibernating bats. Am J Physiology-Regulatory Integr Comp Physiol. 2017;313:R680–6.10.1152/ajpregu.00058.2017 PubMed DOI PMC

Hoyt JR, Sun K, Parise KL, Lu G, Langwig KE, Jiang T et al. Widespread Bat White-Nose Syndrome Fungus, Northeastern China. Emerg Infect Dis. 2015;22. PubMed PMC

Zukal J, Bandouchova H, Brichta J, Cmokova A, Jaron KS, Kolarik M, et al. White-nose syndrome without borders: Pseudogymnoascus destructans infection tolerated in Europe and Palearctic Asia but not in North America. Sci Rep. 2016;6:19829. 10.1038/srep19829 PubMed DOI PMC

Wibbelt G, Kurth A, Hellmann D, Weishaar M, Barlow A, Veith M, et al. White-nose syndrome fungus (Geomyces destructans) in bats, Europe. Emerg Infect Dis. 2010;16:1237–43. 10.3201/eid1608.100002 PubMed DOI PMC

Leopardi S, Blake D, Puechmaille SJ. White-nose syndrome fungus introduced from Europe to North America. Curr Biol. 2015;25:R217–9. 10.1016/j.cub.2015.01.047 PubMed DOI

Martinkova N, Backor P, Bartonicka T, Blazkova P, Cerveny J, Falteisek L, et al. Increasing incidence of Geomyces destructans fungus in bats from the Czech Republic and Slovakia. PLoS ONE. 2010;5:e13853. 10.1371/journal.pone.0013853 PubMed DOI PMC

Fritze M, Costantini D, Fickel J, Wehner D, Czirják GÁ, Voigt CC. Immune response of hibernating European bats to a fungal challenge. Biology Open. 2019;8:1–10. PubMed PMC

Fritze M, Puechmaille SJ, Costantini D, Fickel J, Voigt CC, Czirják GÁ. Determinants of defence strategies of a hibernating European bat species towards the fungal pathogen Pseudogymnoascus destructans. Dev Comp Immunol. 2021. 104017. PubMed

Lilley TM, Prokkola JM, Blomberg AS, Paterson S, Johnson JS, Turner GG et al. Resistance is futile: RNA-sequencing reveals differing responses to bat fungal pathogen in Nearctic Myotis lucifugus and Palearctic Myotis myotis. Oecologia. 2019;:295–309. PubMed PMC

Ayres JS, Schneider DS. Tolerance of infections. Annu Rev Immunol. 2012;30:271–94. 10.1146/annurev-immunol-020711-075030 PubMed DOI

Whiting-Fawcett F, Field KA, Puechmaille SJ, Blomberg AS, Lilley TM. Heterothermy and antifungal responses in bats. Curr Opin Microbiol. 2021;62:61–7. 10.1016/j.mib.2021.05.002 PubMed DOI

Mandl JN, Schneider C, Schneider DS, Baker ML. Going to bat(s) for studies of disease tolerance. Front Immunol. 2018;9. PubMed PMC

Karlsson EK, Kwiatkowski DP, Sabeti PC. Natural selection and infectious disease in human populations. Nat Rev Genet. 2014;15:379–93. 10.1038/nrg3734 PubMed DOI PMC

Yang Z, Bielawski JP. Statistical methods for detecting molecular adaptation. Trends Ecol Evol. 2000;15:496–503. 10.1016/S0169-5347(00)01994-7 PubMed DOI PMC

Harazim M, Horáček I, Jakešová L, Luermann K, Moravec JC, Morgan S, et al. Natural selection in bats with historical exposure to white-nose syndrome. BMC Zool. 2018;3:1–13.10.1186/s40850-018-0035-4 DOI

Wilson DE, Mittermeier RA, editors. Handbook of the mammals of the World. Vol. 9. Bats. Barcelona: Lynx Edicions; 2019.

Blomberg AS, Lilley TM, Fritze M, Puechmaille SJ. Climatic factors and host species composition at hibernation sites drive the incidence of bat fungal disease. 2023;:2023.02.27.529820.

Hecht-Höger AM, Beate CB, Krause E, Meschede A, Krahe R, Voigt CC, et al. Plasma proteomic profiles differ between European and north American myotid bats colonized by Pseudogymnoascus destructans. Mol Ecol. 2020;29:1745–55. 10.1111/mec.15437 PubMed DOI

Cheng TL, Gerson A, Moore MS, Reichard JD, DeSimone J, Willis CKR, et al. Higher fat stores contribute to persistence of little brown bat populations with white-nose syndrome. J Anim Ecol. 2019;88:561–600.10.1111/1365-2656.12954 PubMed DOI

Frick WF, Johnson E, Cheng TL, Lankton JS, Warne R, Dallas J, et al. Experimental inoculation trial to determine the effects of temperature and humidity on white-nose syndrome in hibernating bats. Sci Rep. 2022;12:971. 10.1038/s41598-022-04965-x PubMed DOI PMC

Johnson JS, Reeder DM, Lilley TM, Czirják GÁ, Voigt CC, McMichael JW et al. Antibodies to Pseudogymnoascus destructans are not sufficient for protection against white-nose syndrome. Ecol Evol. 2015;:2203–14. PubMed PMC

Davy CM, Donaldson ME, Willis CKR, Saville BJ, McGuire LP, Mayberry HW, et al. The other white-nose syndrome transcriptome: tolerant and susceptible hosts respond differently to the pathogen pseudogymnoascus destructans. Ecol Evol. 2017;7:7161–70. 10.1002/ece3.3234 PubMed DOI PMC

Willis CKR, Menzies AK, Boyles JG, Wojciechowski MS. Evaporative water loss is a plausible explanation for mortality of bats from white-nose syndrome. Integr Comp Biol. 2011;51:364–73. 10.1093/icb/icr076 PubMed DOI

Donaldson ME, Davy CM, Willis CKR, McBurney S, Park A, Kyle CJ. Profiling the immunome of little brown myotis provides a yardstick for measuring the genetic response to white-nose syndrome. Evol Appl. 2017;10:1076–90. 10.1111/eva.12514 PubMed DOI PMC

Morales AE, Ruedi M, Field K, Carstens BC. Diversification rates have no effect on the convergent evolution of foraging strategies in the most speciose genus of bats, Myotis*. Evolution. 2019;73:2263–80. 10.1111/evo.13849 PubMed DOI

Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 2011;17:10–2.10.14806/ej.17.1.200 DOI

Joshi N, Fass J, Sickle. A sliding-window, adaptive, quality-based trimming tool for FastQ files (Version 1.33) [Software]. https://github.com/najoshi/sickle. 2011.

Lilley TM, Wilson IW, Field KA, Reeder DM, Vodzak ME, Turner GG, et al. Genome-wide changes in genetic diversity in a Population of Myotis lucifugus affected by White-Nose Syndrome. G3: Genes Genomes Genet. 2020;10:2007–20.10.1534/g3.119.400966 PubMed DOI PMC

Andrews S. FastQC A Quality Control tool for High Throughput Sequence Data. 2015.

Schmieder R, Edwards R. Quality control and preprocessing of metagenomic datasets. Bioinformatics. 2011;27:863–4. 10.1093/bioinformatics/btr026 PubMed DOI PMC

Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina Sequence Data. 2014. PubMed PMC

Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9:357–9. 10.1038/nmeth.1923 PubMed DOI PMC

Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, et al. Twelve years of SAMtools and BCFtools. GigaScience. 2021;10:giab008. 10.1093/gigascience/giab008 PubMed DOI PMC

Picard Tools - By Broad Institute. https://broadinstitute.github.io/picard/. Accessed 28 Aug 2023.

Korneliussen TS, Albrechtsen A, Nielsen R. ANGSD: analysis of next generation sequencing data. BMC Bioinformatics. 2014;15:356. 10.1186/s12859-014-0356-4 PubMed DOI PMC

Manni M, Berkeley MR, Seppey M, Simão FA, Zdobnov EM. BUSCO Update: Novel and Streamlined Workflows along with broader and deeper phylogenetic Coverage for Scoring of Eukaryotic, Prokaryotic, and viral genomes. Mol Biol Evol. 2021;38:4647–54. 10.1093/molbev/msab199 PubMed DOI PMC

Levy Karin E, Mirdita M, Söding J. MetaEuk—sensitive, high-throughput gene discovery, and annotation for large-scale eukaryotic metagenomics. Microbiome. 2020;8:48. 10.1186/s40168-020-00808-x PubMed DOI PMC

Katoh K, Standley DM. MAFFT multiple sequence alignment Software Version 7: improvements in performance and usability. Mol Biol Evol. 2013;30:772–80. 10.1093/molbev/mst010 PubMed DOI PMC

Suyama M, Torrents D, Bork P. PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucleic Acids Res. 2006;34 suppl2:W609–12. 10.1093/nar/gkl315 PubMed DOI PMC

Castresana J. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol. 2000;17:540–52. 10.1093/oxfordjournals.molbev.a026334 PubMed DOI

Kriventseva EV, Kuznetsov D, Tegenfeldt F, Manni M, Dias R, Simão FA, et al. OrthoDB v10: sampling the diversity of animal, plant, fungal, protist, bacterial and viral genomes for evolutionary and functional annotations of orthologs. Nucleic Acids Res. 2019;47:D807–11. 10.1093/nar/gky1053 PubMed DOI PMC

Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD, von Haeseler A, et al. IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol. 2020;37:1530–4. 10.1093/molbev/msaa015 PubMed DOI PMC

Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods. 2017;14:587–9. 10.1038/nmeth.4285 PubMed DOI PMC

Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. UFBoot2: improving the Ultrafast bootstrap approximation. Mol Biol Evol. 2018;35:518–22. 10.1093/molbev/msx281 PubMed DOI PMC

Zhang C, Rabiee M, Sayyari E, Mirarab S. ASTRAL-III: polynomial time species tree reconstruction from partially resolved gene trees. BMC Bioinformatics. 2018;19:153. 10.1186/s12859-018-2129-y PubMed DOI PMC

Yang Z. PAML 4: phylogenetic analysis by Maximum Likelihood. Mol Biol Evol. 2007;24:1586–91. 10.1093/molbev/msm088 PubMed DOI

R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/. 2022.

Kim SY, Lohmueller KE, Albrechtsen A, Li Y, Korneliussen T, Tian G, et al. Estimation of allele frequency and association mapping using next-generation sequencing data. BMC Bioinformatics. 2011;12:231. 10.1186/1471-2105-12-231 PubMed DOI PMC

Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011;27:2156–8. 10.1093/bioinformatics/btr330 PubMed DOI PMC

Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841–2. 10.1093/bioinformatics/btq033 PubMed DOI PMC

Alachiotis N, Pavlidis P. RAiSD detects positive selection based on multiple signatures of a selective sweep and SNP vectors. Commun Biol. 2018;1:1–11. 10.1038/s42003-018-0085-8 PubMed DOI PMC

Shumate A, Salzberg SL. Liftoff: accurate mapping of gene annotations. Bioinformatics. 2021;37:1639–43. 10.1093/bioinformatics/btaa1016 PubMed DOI PMC

Dainat J, Murray K, Hereñú D, Davis E, Crouch K, Sol L et al. AGAT: another Gff Analysis Toolkit to handle annotations in any GTF/GFF format. (Version v0.9.2). 2023. 10.5281/zenodo.8178877

Nielsen R, Korneliussen T, Albrechtsen A, Li Y, Wang J. SNP calling, genotype calling, and sample allele frequency estimation from new-generation sequencing data. PLoS ONE. 2012;7:e37558. 10.1371/journal.pone.0037558 PubMed DOI PMC

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards suite: from Gene Data Mining to Disease Genome sequence analyses. Curr Protocols Bioinf. 2016;54:1301–13033.10.1002/cpbi.5 PubMed DOI

Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015;10:845–58. 10.1038/nprot.2015.053 PubMed DOI PMC

Porollo AA, Adamczak R, Meller J. POLYVIEW: a flexible visualization tool for structural and functional annotations of proteins. Bioinformatics. 2004;20:2460–2. 10.1093/bioinformatics/bth248 PubMed DOI

Omasits U, Ahrens CH, Müller S, Wollscheid B. Protter: interactive protein feature visualization and integration with experimental proteomic data. Bioinformatics. 2014;30:884–6. 10.1093/bioinformatics/btt607 PubMed DOI

Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H, et al. G:profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res. 2019;47:W191–8. 10.1093/nar/gkz369 PubMed DOI PMC

Ruedi M, Mayer F. Molecular Systematics of bats of the Genus Myotis (Vespertilionidae) suggests deterministic ecomorphological convergences. Mol Phylogenet Evol. 2001;21:436–48. 10.1006/mpev.2001.1017 PubMed DOI

Ruedi M, Stadelmann B, Gager Y, Douzery EJP, Francis CM, Lin L-K, et al. Molecular phylogenetic reconstructions identify East Asia as the cradle for the evolution of the cosmopolitan genus Myotis (Mammalia, Chiroptera). Mol Phylogenet Evol. 2013;69:437–49. 10.1016/j.ympev.2013.08.011 PubMed DOI

Shi JJ, Rabosky DL. Speciation dynamics during the global radiation of extant bats. Evolution. 2015;69:1528–45. 10.1111/evo.12681 PubMed DOI

Diekmann Y, Pereira-Leal JB. Gene Tree affects inference of sites under Selection by the Branch-Site Test of positive selection. Evol Bioinform Online. 2015;11s2:EBO.S30902. PubMed PMC

Platt RNII, Faircloth BC, Sullivan KAM, Kieran TJ, Glenn TC, Vandewege MW, et al. Conflicting evolutionary histories of the mitochondrial and nuclear genomes in New World Myotis bats. Syst Biol. 2018;67:236–49. 10.1093/sysbio/syx070 PubMed DOI PMC

Foley NM, Harris AJ, Bredemeyer KR, Ruedi M, Puechmaille SJ, Teeling EC et al. Karyotypic stasis and swarming influenced the evolution of viral tolerance in a species-rich bat radiation. Cell Genomics. 2024;4. PubMed PMC

Korstian JM, Paulat NS, Platt RN, Stevens RD, Ray DA. SINE-Based phylogenomics reveal extensive introgression and incomplete lineage sorting in Myotis. Genes. 2022;13:399. 10.3390/genes13030399 PubMed DOI PMC

Mendes FK, Hahn MW. Gene Tree Discordance causes apparent substitution rate variation. Syst Biol. 2016;65:711–21. 10.1093/sysbio/syw018 PubMed DOI

Nielsen R, Yang Z. Likelihood models for detecting positively selected amino acid sites and Applications to the HIV-1 envelope gene. Genetics. 1998;148:929–36. 10.1093/genetics/148.3.929 PubMed DOI PMC

Yang Z, Nielsen R, Goldman N, Pedersen AM. Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics. 2000;155:431–49. 10.1093/genetics/155.1.431 PubMed DOI PMC

Xu D, Jiang W, Wu L, Gaudet RG, Park E-S, Su M, et al. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature. 2023;619:819–27. 10.1038/s41586-023-06322-y PubMed DOI PMC

Croft M. Control of immunity by the TNFR-Related molecule OX40 (CD134). Annu Rev Immunol. 2010;28:57–78. 10.1146/annurev-immunol-030409-101243 PubMed DOI PMC

Chiang LY, Sheppard DC, Gravelat FN, Patterson TF, Filler SG. Aspergillus Fumigatus stimulates leukocyte adhesion molecules and cytokine production by endothelial cells in Vitro and during Invasive Pulmonary Disease. Infect Immun. 2008;76:3429–38. 10.1128/IAI.01510-07 PubMed DOI PMC

Barrios CS, Johnson BD, Henderson D, Fink J, Kelly JN, Kurup KJ. The costimulatory molecules CD80, CD86 and OX40L are up-regulated in aspergillus fumigatus sensitized mice. Clin Exp Immunol. 2005;142:242–50. 10.1111/j.1365-2249.2005.02905.x PubMed DOI PMC

Sánchez-Maldonado JM, Moñiz-Díez A, ter Horst R, Campa D, Cabrera-Serrano AJ, Martínez-Bueno M, et al. Polymorphisms within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis: a two-stage Case Control Study in the context of the aspBIOmics Consortium. J Fungi. 2021;7:4.10.3390/jof7010004 PubMed DOI PMC

Banerjee A, Baker ML, Kulcsar K, Misra V, Plowright R, Mossman K. Novel insights into Immune systems of bats. Front Immunol. 2020;11. PubMed PMC

Hase K, Murakami T, Takatsu H, Shimaoka T, Iimura M, Hamura K, et al. The membrane-bound chemokine CXCL16 expressed on follicle-Associated Epithelium and M cells mediates Lympho-Epithelial Interaction in GALT1. J Immunol. 2006;176:43–51. 10.4049/jimmunol.176.1.43 PubMed DOI

Wilbanks A, Zondlo SC, Murphy K, Mak S, Soler D, Langdon P, et al. Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. J Immunol. 2001;166:5145–54. 10.4049/jimmunol.166.8.5145 PubMed DOI

Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, et al. The transmembrane CXC-Chemokine Ligand 16 is Induced by IFN-γ and TNF-α and shed by the activity of the disintegrin-like Metalloproteinase ADAM10 1. J Immunol. 2004;172:6362–72. 10.4049/jimmunol.172.10.6362 PubMed DOI

Deng M, Li F, Ballif BA, Li S, Chen X, Guo L, et al. Identification and functional analysis of a Novel cyclin E/Cdk2 substrate Ankrd17 *. J Biol Chem. 2009;284:7875–88. 10.1074/jbc.M807827200 PubMed DOI PMC

Wang Y, Tong X, Li G, Li J, Deng M, Ye X. Ankrd17 positively regulates RIG-I-like receptor (RLR)-mediated immune signaling. Eur J Immunol. 2012;42:1304–15. 10.1002/eji.201142125 PubMed DOI

Menning M, Kufer TA. A role for the ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses. FEBS Lett. 2013;587:2137–42. 10.1016/j.febslet.2013.05.037 PubMed DOI

Davy CM, Donaldson ME, Subudhi S, Rapin N, Warnecke L, Turner JM, et al. White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats. Sci Rep. 2018;8:15508. 10.1038/s41598-018-33975-x PubMed DOI PMC

Gerke V, Moss SE, Annexins. From structure to function. Physiol Rev. 2002;82:331–71. 10.1152/physrev.00030.2001 PubMed DOI

Sanches JM, Rossato L, Lice I, Alves de Piloto Fernandes AM, Bueno Duarte GH, Rosini Silva AA, et al. The role of annexin A1 in Candida albicans and Candida Auris infections in murine neutrophils. Microb Pathog. 2021;150:104689. 10.1016/j.micpath.2020.104689 PubMed DOI

Vanessa KHQ, Julia MG, Wenwei L, Michelle ALT, Zarina ZRS, Lina LHK, et al. Absence of Annexin A1 impairs host adaptive immunity against Mycobacterium tuberculosis in vivo. Immunobiology. 2015;220:614–23. 10.1016/j.imbio.2014.12.001 PubMed DOI

Leoni G, Neumann P-A, Kamaly N, Quiros M, Nishio H, Jones HR, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015;125:1215–27. 10.1172/JCI76693 PubMed DOI PMC

Fuller NW, McGuire LP, Pannkuk EL, Blute T, Haase CG, Mayberry HW, et al. Disease recovery in bats affected by white-nose syndrome. J Exp Biol. 2020;223:1–12. PubMed

Mailliard WS, Haigler HT, Schlaepfer DD. Calcium-dependent binding of S100C to the N-terminal domain of annexin I. J Biol Chem. 1996;271:719–25. 10.1074/jbc.271.2.719 PubMed DOI

Sakaguchi M, Murata H, Sonegawa H, Sakaguchi Y, Futami J, Kitazoe M, et al. Truncation of Annexin A1 is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with cytosolic phospholipase A2 in normal and malignant squamous epithelial cells *. J Biol Chem. 2007;282:35679–86. 10.1074/jbc.M707538200 PubMed DOI

Mitra S, Ray SK, Banerjee R. Synonymous codons influencing gene expression in organisms. RRBC. 2016;6:57–65.10.2147/RRBC.S83483 DOI

Brule CE, Grayhack EJ. Synonymous codons: choose wisely for expression. Trends Genet. 2017;33:283–97. 10.1016/j.tig.2017.02.001 PubMed DOI PMC

Barrett LW, Fletcher S, Wilton SD. Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements. Cell Mol Life Sci. 2012;69:3613–34. 10.1007/s00018-012-0990-9 PubMed DOI PMC

Meteyer CU, Barber D, Mandl JN. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome. Virulence. 2012;3. PubMed PMC

Auteri GG, Knowles LL. Decimated little brown bats show potential for adaptive change. Sci Rep. 2020;10:1–10. PubMed PMC

Gignoux-Wolfsohn SA, Pinsky ML, Kerwin K, Herzog C, Hall M, Bennett AB, et al. Genomic signatures of selection in bats surviving white-nose syndrome. Mol Ecol. 2021;30:5643–57. 10.1111/mec.15813 PubMed DOI

Cheng TL, Bennett AB, Teague O’Mara M, Auteri GG, Frick WF. Persist or perish: can bats threatened with extinction persist and recover from white-nose syndrome? Integr Comp Biol. 2024;:icae018. PubMed