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Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00400

The glucan-remodeling enzyme Phr1p and the chitin synthase Chs1p cooperate to maintain proper nuclear segregation and cell integrity in Candida albicans

  • 1University of Milan, Italy

GH72 family of -(1,3)-glucanosyltransferases is unique to fungi and is required for cell wall biogenesis, morphogenesis and virulence, and in some species is essential for life. Candida albicans PHR1 and PHR2 are pH-regulated genes that encode GH72 enzymes highly similar to Gas1p of Saccharomyces cerevisiae. PHR1 is expressed at pH ≥ 5.5 while PHR2 is transcribed at pH ≤ 5.5. Both are essential for C. albicans morphogenesis and virulence. During growth at neutral-alkaline pH, Phr1p-GFP preferentially localizes to sites of active cell wall formation as the incipient bud, the mother-daughter neck, the bud periphery and concentrates in the septum at cytokinesis. We further investigated this latter localization. In chs3 cells, lacking the chitin of the chitin ring and lateral cell wall, Phr1p-GFP still concentrated along the thin line of the primary septum formed by chitin deposited by chitin synthase I (whose catalytic subunit is Chs1p) suggesting that it plays a role during formation of the secondary septa. RO-09-3143, a highly specific inhibitor of Chs1p activity, inhibits septum formation and blocks cell division. However, alternative septa are produced and are crucial for cell survival. Phr1p-GFP is excluded from such aberrant septa. Finally, we determined the effects of RO-09-3143 in cells lacking Phr1p. PHR1 null mutant was more susceptible to the drug than the wild type. The phr1 cells were larger, devoid of septa and underwent endomitosis and cell death. Phr1p and Chs1p cooperate in maintaining cell integrity and in coupling morphogenesis with nuclear division in C. albicans.

Keywords: cell wall assembly, β-(1,3)-glucanosyltransferases, septum, nuclear segregation, Cell integrity, Morphogenesis

Received: 01 Aug 2019; Accepted: 07 Nov 2019.

Copyright: © 2019 Popolo and Degani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Laura Popolo, University of Milan, Milan, Italy,