Candida lusitaniae: Biology, Pathogenicity, Virulence Factors, Diagnosis, and Treatment

Figures & data

Table 1 Prediction of the Most Important Virulence Factors in Candida lusitaniae

Virulence Factor	C. albicans Protein	C. lusitaniae Protein*	E- value	Similarity (%)	Putative Role
Adhesins	Als1-7 and Als9	CLUG_03274 FOB63_002933 EJF14_40078	1e^−46 3e^−74 7e^−44	47 47 51	Adherence of the organism to the oral mucosa.^Citation138
	Ecm33	FOB63_002672	2e^−150	75	Contributes to the integrity of the fungal cell wall.^Citation139
	Iff4	FOB63_003688	4e^−27	47	Involved in cell wall organization, hyphal growth, as well as in host-fungus interaction.^Citation140
	Mp65	FOB63_004871	4e^−119	78	Cell surface mannoprotein involved in cell wall glucan metabolism and adhesion.^Citation141
Biofilm formation	Bcr1	A9F13_15g00066	1e^−39	87	Acts as a master regulator of biofilm formation.^Citation142
	Brg1	CLUG_05535	3e^−47	61	Necessary for hyphal growth and biofilm formation.^Citation78
	Efg1	A9F13_02g02442	2e^−91	87	Transcriptional regulator required for filamentation.^Citation78
	Hsp90	A9F13_09g00462	0.0	95	Regulates several signal transduction pathways and temperature-induced morphogenesis; localizes to the surface of hyphae.^Citation143
	Ndt80	FOB63_000392	3e^−81	55	Necessary for hyphal growth and biofilm formation.^Citation144
	Rob1	E0198_003579	1e^−20	45	Transcription factor involved in biofilm formation.^Citation145
	Zap1	CLUG_02564	7e^−130	52	Negatively regulates the biofilm matrix production.^Citation145
Dimorphism	Cph1	CLUG_02576	1e^−119	60	A transcriptional regulator with a key role in controlling filamentous growth.^Citation77
	Hgc1	CLUG_00968	7e^−117	68	Essential for hyphal morphogenesis^Citation79
	Nrg1	A9F13_05g02552	2e^−32	82	Necessary for filamentation and virulence.^Citation78
	Tup1	A9F13_01g07271	0.0	85	Prevents filamentous growth in the absence of appropriate signals.^Citation78
Immune evasion	Hgt1	E0198_001093	0.0	81	Plays a non-canonical role by down-modulating phagocytosis and killing by human neutrophils.^Citation146
	Msb2	A9F13_12g01265	1e^−71	57	Signaling mucin that allows fungi survival and growth in the infected human host.^Citation147
	Pra1	No found	-	-	Encodes for an antigen associated with the cell wall, known as a fibrinogen binding protein.^Citation148
Proteinase and phospholipase	Lip5-8	EJF14_20550 E0198_001560	3e^−139 7e^−141	62 62	Required for virulence in different infection models.^Citation66
	Sap1-3 Sap5	EJF14_50044 FOB63_000850	3e^−45 2e^−45	49 51	Necessary for active penetration of host cells, neutrophil extracellular traps (NETs)-releasing response. Required for proteolysis.^Citation66
	Plb1-5	CLUG_01525 FOB63_000168	0.0 0.0	68 75	Important for host cell penetration and virulence in a mouse model of systemic infection.^Citation149
Thermotolerance	Hsp60	CLUG_00619	0.0	96	Acts as an immunogenic trigger in orchestrating Candida-related diseases under thermal stress.^Citation82
	Hsp104	CLUG_01501	0.0	90	Pro-survival mediator in response to increasing temperature.^Citation82
	Ssa1	CLUG_01400	0.0	94	Acts as invasin, facilitating host cell endocytosis.^Citation150

Notes: *Protein names are the accession codes of the sequences at the National Center for Biotechnology Information database (https://www.ncbi.nlm.nih.gov/). The putative protein sequence encoded by the C. albicans gene was subjected to a standard protein BLAST analysis at https://www.ncbi.nlm.nih.gov/. The best hit is reported in the C. lusitaniae Protein column, and this was scored with the lowest E value. The similarity column refers to the comparison of amino acid sequences from the C. albicans encoded protein and the best hit.

Figure 1 Schematic representation of the phylogenetic relationship between species of the Candida CTG clade. The species C. rugosa, C lusitaniae, C guilliermondii, C famata, C parapsilosis, C tropicalis, C dubliniensis and C. albicans are part of the CTG clade of Candida. (٭) represents the species of our interest, C lusitaniae, and C. guilliermondii, which are phylogenetically closer to each other. The lengths of the branches are arbitrary.

Kamai Y, Kubota M, Kamai Y, Hosokawa T, Fukuoka T, Filler SG. Contribution of Candida albicans ALS1 to the pathogenesis of experimental oropharyngeal candidiasis. Infect Immun. 2002;70(9):5256–5258. doi:10.1128/IAI.70.9.5256-5258.2002

 Web of Science ®Google Scholar

Gil-Bona A, Reales-Calderon JA, Parra-Giraldo CM, Martinez-Lopez R, Monteoliva L, Gil C. The cell wall protein Ecm33 of Candida albicans is Involved in chronological life span, morphogenesis, cell wall regeneration, stress tolerance, and host–cell interaction. Front Microbiol. 2016;7:64. doi:10.3389/fmicb.2016.00064

 Web of Science ®Google Scholar

Kempf M, Apaire-Marchais V, Saulnier P, et al. Disruption of Candida albicans IFF4 gene involves modifications of the cell electrical surface properties. Colloids Surf B: Biointer. 2007;58(2):250–255. doi:10.1016/j.colsurfb.2007.03.017

 PubMed Web of Science ®Google Scholar

Gomez MJ, Torosantucci A, Arancia S, Maras B, Parisi L, Cassone A. Purification and biochemical characterization of a 65-kilodalton mannoprotein (MP65), a main target of anti-Candida cell-mediated immune responses in humans. Infect Immun. 1996;64(7):2577–2584. doi:10.1128/iai.64.7.2577-2584.1996

 Web of Science ®Google Scholar

Nobile CJ, Mitchell AP. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr Biol. 2005;15(12):1150–1155. doi:10.1016/j.cub.2005.05.047

 PubMed Web of Science ®Google Scholar

Cleary IA, Lazzell AL, Monteagudo C, Thomas DP, Saville SP. BRG1 and NRG1 form a novel feedback circuit regulating Candida albicans hypha formation and virulence. Mol Microbiol. 2012;85(3):557–573. doi:10.1111/j.1365-2958.2012.08127.x

 PubMed Web of Science ®Google Scholar

Burt ET, Daly R, Hoganson D, Tsirulnikov Y, Essmann M, Larsen B. Isolation and partial characterization of Hsp90 from Candida albicans. Ann Clin Lab Sci. 2003;33(1):86–93.

 Web of Science ®Google Scholar

Chen CG, Yang YL, Shih HI, Su CL, Lo HJ. CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1. Antimicrob Agents Chemother. 2004;48(12):4505–4512. doi:10.1128/AAC.48.12.4505-4512.2004

 PubMed Web of Science ®Google Scholar

Araújo D, Henriques M, Silva S. Portrait of Candida species biofilm regulatory network genes. Trends Microbiol. 2017;25(1):62–75. doi:10.1016/j.tim.2016.09.004

 PubMed Web of Science ®Google Scholar

Braun BR, Johnson AD. TUP1, CPH1 and EFG1 make independent contributions to filamentation in Candida albicans. Genetics. 2000;155(1):57–67. doi:10.1093/genetics/155.1.57

 PubMed Web of Science ®Google Scholar

Zheng X, Wang Y, Wang Y. Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis. EMBO J. 2004;23(8):1845–1856. doi:10.1038/sj.emboj.7600195

 PubMed Web of Science ®Google Scholar

Kenno S, Speth C, Rambach G, et al. Candida albicans factor H binding molecule Hgt1p – a low glucose-induced transmembrane protein is trafficked to the cell wall and impairs phagocytosis and killing by human neutrophils. Front Microbiol. 2019;9:3319. doi:10.3389/fmicb.2018.03319

 Web of Science ®Google Scholar

Swidergall M, Ernst AM, Ernst JF. Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides. Antimicrob Agents Chemother. 2013;57(8):3917–3922. doi:10.1128/AAC.00862-13

 Web of Science ®Google Scholar

Marcil A, Gadoury C, Ash J, Zhang J, Nantel A, Whiteway M. Analysis of PRA1 and its relationship to Candida albicans- macrophage interactions. Infect Immun. 2008;76(9):4345–4358. doi:10.1128/IAI.00588-07

 Web of Science ®Google Scholar

Staniszewska M. Virulence factors in Candida species. Curr Protein Pept Sci. 2020;21(3):313–323. doi:10.2174/1389203720666190722152415

 Web of Science ®Google Scholar

Leidich SD, Ibrahim AS, Fu Y, et al. Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J Biol Chem. 1998;273(40):26078–26086. doi:10.1074/jbc.273.40.26078

 PubMed Web of Science ®Google Scholar

Gong Y, Li T, Yu C, Sun S. Candida albicans heat shock proteins and Hsps-associated signaling pathways as potential antifungal targets. Front Cell Infect Microbiol. 2017;7(520):520. doi:10.3389/fcimb.2017.00520

 Web of Science ®Google Scholar

Sun JN, Solis NV, Phan QT, et al. Host cell invasion and virulence mediated by Candida albicans Ssa1. PLoS Pathog. 2010;6(11):e1001181. doi:10.1371/journal.ppat.1001181

 PubMed Web of Science ®Google Scholar