Correction to: Functional & Integrative Genomics

In the original version of the manuscript, there are missing captions for Figures 2 and 3. Additionally, three references need to be added to Table 1.

If fungal TCSs operate mainly or solely through phosphorelays, a fundamental question arises: how do multiple histidine kinases (HHKs) detect diverse stimuli and transfer phosphoryl groups via a single histidine phosphotransfer protein (Hpt), Ypd1, to a limited number of response regulators (Skn7, Ssk1, Srr1) while ensuring specificity in signaling? Proposed mechanisms, such as employing scaffolding proteins or splice variants to maintain signal fidelity through Ypd1, may shift the bottleneck but fail to resolve the core issue of having numerous HHKs yet only a few response regulators. The most straightforward explanation is that only osmotic stress and closely related pathways rely on a phosphorelay system, while the majority of fungal TCSs follow alternative signaling routes. This perspective accounts for the conserved nature of Hpts and response regulators across fungal species. The key reactions involved include: (1) autophosphorylation of the sensor kinase, (2) histidine-to-aspartate phosphotransfer, and (3) aspartate-to-histidine phosphotransfer. For simplicity, reversible reactions and dephosphorylation steps are excluded from this discussion

Comprehensive illustration of fungal two-component signaling systems (TCSs). Multiple histidine kinases (HHKs) sense different signals but transfer phosphate through a single protein, Ypd1, to only a few response regulators (Skn7, Ssk1). This raises questions about how signal specificity is maintained. Only osmotic stress-related signals and strongly linked pathways likely use this phosphorelay, while other pathways may follow different routes. Key steps include kinase autophosphorylation and phosphate transfer between histidine and aspartate residues. However, reversible steps and dephosphorylation are not shown. This Figure 2 is adapted with change in color scheme and shape of the boxes of Figure 2 of the article entitled “A radical reimagining of fungal Two-Component regulatory systems by Bourret et al. 2021. Trends Microbiol 29(10):883–893”. https://doi.org/10.1016/j.tim.2021.03.005

The following sentences have been added in the Figure captions for figures 2 and 3.

The Figure 2 is adapted with minor alterations in Figure 2 of the article entitled “A radical reimagining of fungal Two-Component regulatory systems by Bourret et al. 2021, Trends Microbiol 29(10):883–893. https://doi.org/10.1016/j.tim.2021.03.005

The Figure 3 is adapted with minor modifications in Figure 3 of the article entitled “The two-component signal transduction system and its regulation in Candida albicans by Liao et al. 2021. Virulence 12(1):1884-1899. DOI: 10.1080/21505594.2021.1949883

The complete caption for Figure 3 is shown below.

The two-component systems (TCS) and their downstream signaling pathways exhibit variations among different fungal species. In most eukaryotes, TCS follows a multistep phosphotransfer model. However, the structure and signal transduction mechanisms of these systems differ across fungi. For instance, Saccharomyces cerevisiae possesses a single histidine protein kinase (HPK), while Candida albicanshas three HPKs, and Cryptococcus neoformans contains seven. The phosphorylation state of an HPK influences the phosphorylation efficiency of response regulators (RRs). In some cases, multiple HPKs regulate a single RR, whereas a single HPK can also control multiple RRs. The Figure 3 is adapted with minor modifications in color scheme and shape of boxes of Figure 3 of the article entitled “The two-component signal transduction system and its regulation in Candida albicans by Liao et al. 2021. Virulence 12(1):1884”. DOI: 10.1080/21505594.2021.1949883

The references that are missing in table 1 (column 5 (references), rows 2-4) are as follows including the full bibliographic details and also needs to be added in the reference list:

Mochochoko bm, pohl ch, o’neill hg (2023). Candida albicans-enteric viral interactions—the prostaglandin e2 connection and host immune responses. iscience 26(1). https://doi.org/10.1016/j.isci.2022.105870

Haas-Stapleton EJ, Lu Y, Hong S, Arita M, Favoreto S, Nigam S, Serhan CN, Agabian N (2007). Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1. PLoS ONE 2(12), e1316. https://doi.org/10.1371/journal.pone.0001316

Mare L, Iatta R, Montagna MT, Luberto C, Del Poeta M (2005). APP1 transcription is regulated by inositol-phosphorylceramide synthase 1-diacylglycerol pathway and is controlled by ATF2 transcription factor in Cryptococcus neoformans. J Biol Chem 280(43), 36055-36064. DOI: 10.1074/jbc.M507285200

Conflict of Interest: Dr Mehboob-ur-Rahman is a member of the Editorial Board of “Functional & Integrative Genomics”.

The original article has been corrected.