Biolm development is a highly regulated process controlled by a complex net­work of transcription factors that govern various pathways and downstream target genes, each playing a specic role in the different stages of biolm development.

The transcriptional network identied by Nobile etal. consists of six key tran­scriptional factor networks, namely, EFG1, TEC1, NDT80, BCR1, ROB1, and BRG1. Disruption of any of these transcription factors results in defective biolm formation. Each transcription factor is involved at a specic stage of biolm formation (Nobile etal. 2012). BCR1 is mainly involved during the adherence of pathogens to a suitable substratum. Als1, Als3, and Hwp1 are under the control of BCR1. ∆bcr1/∆bcr1 showed a decreased expression of Als3 and Hwp1 and also developed a thin biolm. TEC1 controls the expression of BCR1, which ne-tunes the downstream adhesion genes. TEC1 is regulated by EFG1, which is involved in lamentous growth. Biolm maturation is handled by NDT80, ROB1, and BRG1 (Araújo etal. 2017).

Predicted GPI anchored protein, Pga59 initiates attachment through the forma­tion of amyloid brils. It contains 42 amino acids long stretch, which shows beta aggregation potential. This amyloid-mediated adhesion is essential for C. albicans to promote attachment to substrates (Mourer etal. 2023).

Candida species employ extracellular hydrolytic enzymes to enhance their viru­lence. Phospholipases are key players in this strategy, as they hydrolyze phospholip­ids into fatty acids and other lipophilic products. They are ubiquitously present and aid in penetrating and breaking down of the host cell by cleaving ester bonds of phospholipids. Phospholipase can be categorized into four kinds A, B, C, and D, those are encoded by following genes PLA, PLB1, PLB2, PLC1, PLC2, PLC3, and PLD1. In C. albicans, these genes are extensively studied but in non-albicans spe- cies, more experimental studies are required especially with reference to virulence and pathogenesis. Phospholipase A helps in the removal of one of the two esteried fatty acids of glycerol. However, phospholipase B removes both the fatty acid chains at once. B1 and B2 play an important role in host cell destruction. Phospholipase C cleaves the carbon-phosphate bond of phosphatidylcholine releasing phosphoryl­choline and diacylglyceride. It also plays a role in signal transduction. Phospholipase D helps in the release of choline from phosphatidylcholine to release phosphatidic acid (Tanju etal. 2001). Phospholipase activity has also correlated to virulence; in 97% of C. albicans strains isolated from denture stomatitis, patients showed higher phospholipase activity and C. dubliniensis showed moderate activity (Marcos-Arias etal. 2011). The murine model of disseminated candidiasis showed positive correla- tion between higher virulence and phospholipase activity (Ibrahim etal. 1995). Fluconazole resistant strains showed higher phospholipase activity (Ying and Chunyang 2012). In C. albicans, 30–100% strains are reported to produce phospho­lipase (Tsang et al. 2007). Non-albicans species like C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis are known to produce phospholipase. Aforementioned studies substantiate that phospholipase can be a potential biomarker for systemic infection.

Proteinase hydrolyzes peptide bonds in proteins, and they differ in their mechanism of action; hence, they are classied according to their mechanism of catalysis. Proteinase can be distinguished into four classes: (a) serine proteinase, e.g., trypsin, chymotrypsin, and subtilisin, (b) aspartyl proteinase, e.g., HIV aspartyl proteinase, and pepsin and renin in humans, (c) cysteine proteinase, e.g., streptococcal protein­ase and papain, and (d) metalloproteinase, e.g., collagenases and microvillus pro­teinases (Naglik etal. 2003). SAP proteinase contributes to the virulence of the fungus and increases penetration and colonization of host tissue. These proteinases are also involved in adherence, phenotypic switching, and biolm formation, and they are also crucial for hyphal formation and involved in defence from the host immune system (Kadry etal. 2018; Veni etal. 2022; Wu etal. 2016; Zaugg etal.

Lipases, carboxylic ester hydrolases aid in nutrient acquisition through lipid diges­tion. They are carboxylic ester hydrolases and can also be termed as triacylglycerol hydrolases. They hydrolyze triglycerides into diglycerides releasing monoglycer­ides, fatty acids, and glycerol. Lipases are reported to have role in adhesion to host tissue and also initiating inammation (Inci etal. 2012; Khedidja and Abderrahman

Candida albicans, a leading human fungal pathogen, deploys various virulence fac­tors to transition from a commensal to a pathogenic state. Among these factors, Candidalysin stands out as the rst amino acid peptide toxin discovered in any human fungal pathogen. This remarkable toxin plays a crucial role in the host­pathogen interaction and pathogenesis. Library screening of C. albicans for those mutants which can form hypha but unable to induce damage, cytokines or cFOS/ MAPK signalling led to the discovery of Candidalysin. Interestingly, single mutant, ECE1 (extent of elongation), was identied with such specic characteristics (Moyes etal. 2016). Ece1p protein has 271 amino acids (Birse etal. 1993). It pos­sesses seven arginine-lysine (KR) motif which is dispersed throughout the total pro­tein. These KR motifs are cleaved by Kexin (Kex2p) which can cleave the whole peptide into eight sites. Later on, site-directed mutagenesis studies showed that Kex2p cleaves the peptide from Arg61 and Arg93 producing 32 amino acid long peptide which was indispensable for damage induction. The peptide was α-helical,

etal. 2016). Interestingly, other pathogenic species such as C. glabrata, C. parapsi- losis, and C. auris do not harbor candidalysin or Ece1p or orthologs. C. tropicalis and C. dubliniensis candidalysin are reported to have enhanced cytolytic and immu- nostimulatory effect as compared to C. albicans; however, both the aforementioned species are less pathogenic than C. albicans (Richardson et al. 2022). While Candidalysin plays a central role in C. albicans pathogenicity, its orthologs diverse effects in other Candida species highlight the complexity of host-fungal interac­tions and the need for further research in this area.