{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:47:31Z","timestamp":1762660051041,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BII-BIO\/28216\/2017","UIDB\/04565\/2020"],"award-info":[{"award-number":["PTDC\/BII-BIO\/28216\/2017","UIDB\/04565\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Candida glabrata is an emerging fungal pathogen whose success depends on its ability to resist antifungal drugs but also to thrive against host defenses. In this study, the predicted multidrug transporter CgTpo4 (encoded by ORF CAGL0L10912g) is described as a new determinant of virulence in C. glabrata, using the infection model Galleria mellonella. The CgTPO4 gene was found to be required for the C. glabrata ability to kill G. mellonella. The transporter encoded by this gene is also necessary for antimicrobial peptide (AMP) resistance, specifically against histatin-5. Interestingly, G. mellonella\u2019s AMP expression was found to be strongly activated in response to C. glabrata infection, suggesting AMPs are a key antifungal defense. CgTpo4 was also found to be a plasma membrane exporter of polyamines, especially spermidine, suggesting that CgTpo4 is able to export polyamines and AMPs, thus conferring resistance to both stress agents. Altogether, this study presents the polyamine exporter CgTpo4 as a determinant of C. glabrata virulence, which acts by protecting the yeast cells from the overexpression of AMPs, deployed as a host defense mechanism.<\/jats:p>","DOI":"10.3390\/ijms22031376","type":"journal-article","created":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T06:22:20Z","timestamp":1611987740000},"page":"1376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of CgTpo4 in Polyamine and Antimicrobial Peptide Resistance: Determining Virulence in Candida glabrata"],"prefix":"10.3390","volume":"22","author":[{"given":"Mafalda","family":"Cavalheiro","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"given":"Daniela","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"given":"Rui","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-3579","authenticated-orcid":false,"given":"Dalila","family":"Mil-Homens","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-416X","authenticated-orcid":false,"given":"Pedro","family":"Pais","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"given":"Catarina","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"given":"M\u00f3nica","family":"Galocha","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-6163","authenticated-orcid":false,"given":"Diana","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-4654","authenticated-orcid":false,"given":"Azusa","family":"Takahashi-Nakaguchi","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center (MMRC), Chiba University, Chiba 263-8522, Japan"}]},{"given":"Hiroji","family":"Chibana","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center (MMRC), Chiba University, Chiba 263-8522, Japan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-5787","authenticated-orcid":false,"given":"Ars\u00e9nio M.","family":"Fialho","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-6174","authenticated-orcid":false,"given":"Miguel C.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal"},{"name":"Biological Sciences Research Group, IBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, 1049-001 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/myc.12330","article-title":"Antifungal drug resistance among Candida species: Mechanisms and clinical impact","volume":"58","author":"Sanguinetti","year":"2015","journal-title":"Mycoses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1128\/AAC.01256-09","article-title":"Echinocandin Susceptibility Testing of Candida Species: Comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, Disk Diffusion, and Agar Dilution Methods with RPMI and IsoSensitest Media","volume":"54","author":"Arendrup","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/13693780701218689","article-title":"Nosocomial fungal infections: Epidemiology, diagnosis, and treatment","volume":"45","author":"Perlroth","year":"2007","journal-title":"Med. Mycol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3390\/ph4010169","article-title":"Pathogenesis and Antifungal Drug Resistance of the Human Fungal Pathogen Candida glabrata","volume":"4","author":"Tscherner","year":"2011","journal-title":"Pharmaceuticals"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1126\/science.aaa6097","article-title":"How to bolster the antifungal pipeline","volume":"347","author":"Denning","year":"2015","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1128\/CMR.12.1.80","article-title":"Candida glabrata: Review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans","volume":"12","author":"Fidel","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1556\/amicr.54.2007.3.1","article-title":"Pathogenicity and drug resistance in Candida albicans and other yeast species","volume":"54","author":"Mishra","year":"2007","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"fov042","DOI":"10.1093\/femsyr\/fov042","article-title":"Intracellular survival of Candida glabrata in macrophages: Immune evasion and persistence","volume":"15","author":"Kasper","year":"2015","journal-title":"FEMS Yeast Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1574-6976.2011.00278.x","article-title":"Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance","volume":"36","author":"Silva","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Peters, B.M., Shirtliff, M.E., and Jabra-Rizk, M.A. (2010). Antimicrobial peptides: Primeval molecules or future drugs?. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001067"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3390\/jof1020277","article-title":"Candida glabrata, Friend and Foe","volume":"1","author":"Tam","year":"2015","journal-title":"J. Fungi"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1128\/MMBR.00045-10","article-title":"Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease","volume":"75","author":"Shapiro","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1074\/mcp.M114.045344","article-title":"Membrane Proteome-Wide Response to the Antifungal Drug Clotrimazole in Candida glabrata: Role of the Transcription Factor CgPdr1 and the Drug:H+ Antiporters CgTpo1_1 and CgTpo1_2","volume":"15","author":"Pais","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphys.2014.00197","article-title":"MFS multidrug transporters in pathogenic fungi: Do they have real clinical impact?","volume":"5","author":"Costa","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1042\/bj3530681","article-title":"Multiple polyamine transport systems on the vacuolar membrane in yeast","volume":"353","author":"Tomitori","year":"2001","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.gene.2006.08.010","article-title":"The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata","volume":"386","author":"Chen","year":"2007","journal-title":"Gene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1093\/jac\/dku044","article-title":"Candida glabrata drug:H+ antiporter CgTpo3 (ORF CAGL0I10384g): Role in azole drug resistance and polyamine homeostasis","volume":"69","author":"Costa","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2013.00170","article-title":"The dual role of Candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance","volume":"4","author":"Costa","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2016.02045","article-title":"Membrane proteomics analysis of the Candida glabrata response to 5-flucytosine: Unveiling the role and regulation of the drug efflux transporters CgFlr1 and CgFlr2","volume":"7","author":"Pais","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_20","first-page":"1","article-title":"A New Determinant of Candida glabrata Virulence: The Acetate Exporter CgDtr1","volume":"7","author":"Cavalheiro","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1128\/iai.63.11.4515-4518.1995","article-title":"Reduced virulence of Candida albicans mutants affected in multidrug resistance","volume":"63","author":"Becker","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1042\/BJ20140010","article-title":"Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans","volume":"460","author":"Shah","year":"2014","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1574-6968.2002.tb11238.x","article-title":"Characterization of the CaNAG3, CaNAG4, and CaNAG6 genes of the pathogenic fungus Candida albicans: Possible involvement of these genes in the susceptibilities of cytotoxic agents","volume":"212","year":"2002","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cmi.12686","article-title":"The multidrug resistance transporters CgTpo1_1 and CgTpo1_2 play a role in virulence and biofilm formation in the human pathogen Candida glabrata","volume":"19","author":"Santos","year":"2017","journal-title":"Cell. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cavalheiro, M., Pais, P., Galocha, M., and Teixeira, M.C. (2018). Host-pathogen interactions mediated by MDR transporters in fungi: As pleiotropic as it gets!. Genes, 9.","DOI":"10.3390\/genes9070332"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","article-title":"Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing","volume":"7","author":"Tsai","year":"2016","journal-title":"Virulence"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20438","DOI":"10.1074\/jbc.273.32.20438","article-title":"Candidacidal activity of salivary histatins. Identification of a histatin 5-binding protein on Candida albicans","volume":"273","author":"Edgerton","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12820","DOI":"10.1074\/jbc.M210715200","article-title":"Localization and function of the yeast multidrug transporter Tpo1p","volume":"278","author":"Albertsen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"43748","DOI":"10.1074\/jbc.M111.311175","article-title":"Histatin 5 Uptake by Candida albicans Utilizes Polyamine Transporters Dur3 and Dur31 Proteins","volume":"286","author":"Kumar","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1128\/IAI.73.7.4161-4170.2005","article-title":"Superoxide Production in Galleria mellonella Hemocytes: Identification of Proteins Homologous to the NADPH Oxidase Complex of Human Neutrophils","volume":"73","author":"Bergin","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0017589","article-title":"Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata","volume":"6","author":"Ferrari","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jemel, S., Guillot, J., Kallel, K., Botterel, F., and Dannaoui, E. (2020). Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030390"},{"key":"ref_33","first-page":"171","article-title":"Primer on the Immune System","volume":"37","author":"Spiering","year":"2015","journal-title":"Alcohol Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6124","DOI":"10.1128\/AEM.02044-13","article-title":"The virulence of Salmonella enterica Serovar Typhimurium in the insect model Galleria mellonella is impaired by mutations in RNase E and RNase III","volume":"79","author":"Viegas","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1128\/IAI.00510-12","article-title":"Legionella pneumophila Pathogenesis in the Galleria mellonella Infection Model","volume":"80","author":"Harding","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.dci.2010.06.005","article-title":"A different repertoire of Galleria mellonella antimicrobial peptides in larvae challenged with bacteria and fungi","volume":"34","author":"Mak","year":"2010","journal-title":"Dev. Comp. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.micres.2016.10.003","article-title":"Galleria mellonella lysozyme induces apoptotic changes in Candida albicans cells","volume":"193","author":"Wydrych","year":"2016","journal-title":"Microbiol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/arch.10091","article-title":"Cloning and expression of gallerimycin, an antifungal peptide expressed in immune response of greater wax moth larvae, Galleria mellonella","volume":"53","author":"Schuhmann","year":"2003","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1515\/BC.2006.071","article-title":"Transgenic expression of gallerimycin, a novel antifungal insect defensin from the greater wax moth Galleria mellonella, confers resistance to pathogenic fungi in tobacco","volume":"387","author":"Langen","year":"2006","journal-title":"Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.archoralbio.2006.06.005","article-title":"Oral fluid proteolytic effects on histatin 5 structure and function","volume":"51","author":"Helmerhorst","year":"2006","journal-title":"Arch. Oral Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1128\/AAC.02295-12","article-title":"Candida albicans Flu1-Mediated Efflux of Salivary Histatin 5 Reduces Its Cytosolic Concentration and Fungicidal Activity","volume":"57","author":"Li","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Santos, R., Cavalheiro, M., Costa, C., Takahashi-Nakaguchi, A., Okamoto, M., Chibana, H., and Teixeira, M.C. (2020). Screening the Drug:H+ Antiporter Family for a Role in Biofilm Formation in Candida glabrata. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00029"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1128\/EC.00290-06","article-title":"Saccharomyces cerevisiae multidrug resistance transporter Qdr2 is implicated in potassium uptake, providing a physiological advantage to quinidine-stressed cells","volume":"6","author":"Vargas","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1099\/mic.0.043661-0","article-title":"Yeast response and tolerance to polyamine toxicity involving the drug: H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4","volume":"157","author":"Teixeira","year":"2011","journal-title":"Microbiology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Asai, Y., Itoi, T., Sugimoto, M., Sofuni, A., Tsuchiya, T., Tanaka, R., Tonozuka, R., Honjo, M., Mukai, S., and Fujita, M. (2018). Elevated polyamines in saliva of pancreatic cancer. Cancers, 10.","DOI":"10.20944\/preprints201801.0092.v1"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1128\/EC.00414-06","article-title":"Development of a Highly Efficient Gene Targeting System Induced by Transient Repression of YKU80 Expression in Candida glabrata","volume":"6","author":"Ueno","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1080\/21505594.2020.1839231","article-title":"A new regulator in the crossroads of oxidative stress resistance and virulence in Candida glabrata: The transcription factor CgTog1","volume":"11","author":"Pais","year":"2020","journal-title":"Virulence"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.gene.2004.10.016","article-title":"Drag&Drop cloning in yeast","volume":"344","author":"Jansen","year":"2005","journal-title":"Gene"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1128\/AAC.00811-12","article-title":"Candida glabrata drug:H+ antiporter CgQdr2 confers imidazole drug resistance, being activated by transcription factor CgPdr1","volume":"57","author":"Costa","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Vyas, V.K., Bushkin, G.G., Bernstein, D.A., Getz, M.A., Sewastianik, M., Barrasa, M.I., Bartel, D.P., and Fink, G.R. (2018). New CRISPR Mutagenesis Strategies Reveal Variation in Repair Mechanisms among Fungi. mSphere, 3.","DOI":"10.1128\/mSphere.00154-18"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Mil-Homens, D., and Fialho, A.M. (2012). A BCAM0223 Mutant of Burkholderia cenocepacia Is Deficient in Hemagglutination, Serum Resistance, Adhesion to Epithelial Cells and Virulence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041747"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0005-2736(96)00245-3","article-title":"Effect of extracellular acidification on the activity of plasma membrane ATPase and on the cytosolic and vacuolar pH of Saccharomyces cerevisiae","volume":"1325","author":"Carmelo","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.dci.2006.03.002","article-title":"Metamorphosis and collagen-IV-fragments stimulate innate immune response in the greater wax moth, Galleria mellonella","volume":"30","author":"Altincicek","year":"2006","journal-title":"Dev. Comp. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jinsphys.2009.01.014","article-title":"Humoral immune response of Galleria mellonella larvae after infection by Beauveria bassiana under optimal and heat-shock conditions","volume":"55","author":"Wojda","year":"2009","journal-title":"J. Insect Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.imlet.2016.04.013","article-title":"Galleria mellonella larvae are capable of sensing the extent of priming agent and mounting proportionatal cellular and humoral immune responses","volume":"174","author":"Wu","year":"2016","journal-title":"Immunol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:17:25Z","timestamp":1760159845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,29]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031376"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031376","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,1,29]]}}}