The role of the histidine kinase [) gene in the regulation of cell wall mannan and glucan biosynthesis

Kruppa, Michael; Goins, Tresa; Cutler, Jim E.; Lowman, Douglas W.; Williams, David L.; Chauhan, Neeraj; Menon, Veena; Singh, Praveen; Li, Dongmei; Calderone, Richard

doi:10.1016/s1567-1356(02)00164-2

Cited by 21 publications

(48 citation statements)

References 38 publications

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“…We have shown that the chk1 mutant has profound changes in the composition of its cell wall, including levels of 1,3-b-glucan (about 50 % lower) and 1,6-b-glucan (about fourfold higher), as well as a truncation in the oligosaccharide side chains of the acid-stable mannan (Kruppa et al, 2003(Kruppa et al, , 2004b. These changes have been confirmed by both biochemical and immunological determinations.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the quorum sensing pathway which is induced by the isoprenoid farnesol is activated via Chk1p and does not require the HOG1 MAP kinase pathway (Kruppa et al, 2004b). Another major function of Chk1p is its regulatory activity in cell wall biosynthesis (Kruppa et al, 2003(Kruppa et al, , 2004b). This activity is, like the farnesol pathway, independent of HOG1, since the ssk1 mutant does not exhibit the same cell wall phenotype as the chk1 mutant.…”

Section: Discussionmentioning

confidence: 99%

“…Sln1p, Ypd1p and Ssk1p are probably orthologues of the HOG1 MAP kinase pathway proteins [hyperosmotic glycerol] that in Saccharomyces cerevisiae are used for the adaptation of cells to osmotic stress (Hohmann, 2002). In C. albicans these proteins have additional functions which include adaptation to oxidant stress, morphogenesis, virulence, adherence and cell wall biosynthesis (Alex et al, 1998;Alonso-Monge et al, 1999, 2003Bernhardt et al, 2001;Calera et al, 1998Calera et al, , 1999Calera et al, , 2000aCalera & Calderone, 1999a;Chauhan et al, 2003;Kruppa et al, 2003Kruppa et al, , 2004bLi et al, 2002;Nagahashi et al, 1998;Selitrennikoff et al, 2001;Singh et al, 2004;Srikantha et al, 1998;Torosantucci et al, 2002;Yamada-Okabe et al, 1999). All of the two-component genes except SKN7 have been implicated in the virulence of the organism in a haematogenously disseminated murine model.…”

Section: Introductionmentioning

confidence: 99%

“…In that organism, these proteins are used for adaptation to oxidant stress (Buck et al, 2001). C. albicans strains deleted of CHK1 have an altered cell wall phenotype characterized by a truncation of acid-stable cell wall mannan side chains, as well as a reduction in the amount of 1,3-b-glucan and an increase in the amount of 1,6-b-glucan (Kruppa et al, 2003). The primary lesion of the chk1 null mutant has not been defined and is currently being investigated.…”

Section: Introductionmentioning

confidence: 99%

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Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene

2004

Microbiology

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The two-component histidine kinase Chk1p of Candida albicans has been implicated in the regulation of cell wall biosynthesis. Deletion of CHK1 results in avirulence that in part may be due to the increased sensitivity of mutant strains to polymorphonuclear leukocytes. The mutant also does not adhere to human oesophageal tissue in vitro, probably as a consequence of its altered cell wall. In the current study, a CHK1 promoter-lacZ reporter (CHK1prlacZ) construct was expressed in wild-type C. albicans strain CAI4 and in two-component signal transduction mutants to determine the effect of environmental stress conditions on the regulation of CHK1 and the co-regulatory activities among these proteins. It is shown that lacZ expression varied according to the type of growth conditions and incubation time; expression was also influenced by the strain background. lacZ expression in CAI4 was greater at 37 6C and at a pH of 3?5 and in the presence of 4 mM H 2 O 2 , 0?1 mM menadione, 10 % serum or 1?5 M NaCl compared to cells grown at 30 or 42 6C. The increases in expression were time-dependent and not observed until cells were incubated for 120 min in these conditions (P<0?05). As a correlate of the increase in transcription of CHK1-lacZ in the presence of H 2 O 2 , the chk1 mutant was more sensitive than wild-type and revertant cells to H 2 O 2 in vitro. In addition to strain CAI4, we also measured CHK1p-lacZ reporter activity of mutants deleted in genes encoding other two-component proteins such as the response regulator gene SSK1, the histidine kinases, SLN1 and NIK1, and the HOG1 MAP kinase. Of these proteins, Ssk1p and Sln1p are presumed to mediate phosphotransfer to the HOG1 [hyperosmotic glycerol] MAP kinase pathway during oxidative and perhaps osmotic stress in C. albicans. Compared to strain CAI4, lacZ reporter activity increased significantly in the ssk1 mutant under all growth conditions after a 10 and 120 min incubation (P<0?0001). lacZ expression in the ssk1 mutant was less at 42 6C compared to all other growth conditions (P<0?05). Furthermore, lacZ reporter activity also increased in the hog1 mutant of C. albicans. These data suggest that SSK1 and HOG1 indirectly or directly negatively regulate CHK1 under most growth conditions tested. In the sln1 mutant, downregulation of CHK1 was observed in all growth conditions compared to strain CAI4 (P<0?05), while regulation of lacZ in the nik1 mutant was similar to strain CAI4 except when cells were incubated in the presence of 4 mM H 2 O 2 for 120 min (P<0?05). Western blot analysis was used to determine the role of Chk1p in phosphorylation of Hog1p under oxidative or osmotic stress. It was found that Hog1p was phosphorylated in the chk1 mutant similar to wild-type CAF2-1 cells, although the temporal events of phosphorylation differed slightly in mutant cells. These results show that transcription of CHK1, as measured by the lacZ reporter assay, is statistically increased when cells are exposed to several types of stress or when incubated in 10 % serum in a mutant-sp...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene

2004

Microbiology

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“…Calera and co-workers reported the isolation of Ypd1 (Calera et al, 2000a) and the Ssk1 response regulator (Calera et al, 2000b), a member of a two-component signal-transduction pathway that was recently shown to play a role in the transmission of oxidative stress (Chauhan et al, 2003). The role of other putative components is not clear (Chauhan et al, 2003; YamadaOkabe et al, 1999), despite their role in cell-wall construction (Kruppa et al, 2003(Kruppa et al, , 2004Yamada-Okabe et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans

et al. 2005

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The human fungal pathogen Candida albicans responds to stress by phosphorylation of the Hog1 MAP kinase. PBS2 was cloned and shown to encode the MAP kinase kinase that is involved in this activation, as determined by immunoblot analyses using antibodies that recognize the active form of the target Hog1 protein. Characterization of pbs2 mutants revealed that they were sensitive to both osmotic and oxidative stress and that they, interestingly, displayed differential behaviour from that of hog1 mutants, losing viability when exposed to an oxidative challenge more rapidly than the hog1 strain. Hog1 and Pbs2 were also shown to be involved in the mechanism of adaptation to oxidative stress, as evidenced by the enhanced susceptibility to oxidants of pbs2 and hog1 mutants, compared with the wild-type strain, when cells were previously exposed to a low, sub-lethal concentration of hydrogen peroxide and by the PBS2-dependent diminished activation of Hog1 MAP kinase in the adaptive process. Studies with a chimaeric Hog1-green fluorescent protein fusion revealed that this protein was localized throughout the cell (being excluded from the vacuole), but concentrated in the nucleus in response to NaCl stress, a process that was dependent on the Pbs2 protein. Both Hog1 and Pbs2 also play a role in controlling the phosphorylation state of the other MAP kinases Mkc1 and Cek1, involved respectively in cell-wall integrity and invasive growth. Furthermore, it is demonstrated that PBS2 plays a role in cell-wall biogenesis in this fungal pathogen, as its deletion renders cells with an altered susceptibility to certain cell wall-interfering compounds. INTRODUCTIONEukaryotic cells respond to environmental changes through signal-transduction pathways. MAPK (mitogen-activated protein kinase) routes consist of a three-kinase module: the MAP kinase kinase kinase, the MAP kinase kinase and the MAP kinase, which are activated by sequential phosphorylation in response to different extracellular signals. These pathways are conserved through evolution (Kültz & Burg, 1998) and their functionality is well-documented in some model organisms, such as Saccharomyces cerevisiae and Schizosaccharomyces pombe (Banuett, 1998;Gustin et al., 1998). In budding yeast, six MAPK pathways have been described that perform essential functions in fungal physiology, such as mating, pseudohyphal/invasive growth, cellwall integrity, STE vegetative growth (SVG), spore-wall assembly and adaptation to high osmolarity (HOG) (Gustin et al., 1998;Posas et al., 1998). This last route is activated in response to osmotic and -as described recently -oxidative stress (Haghnazari & Heyer, 2004;Singh, 2000) and mutant cells in some elements of the pathway are sensitive to both kinds of stresses. Osmosensitivity is partially explained by the inability to increase intracellular glycerol under restrictive conditions in order to counteract the extracellular turgor (Albertyn et al., 1994). Under hyperosmotic conditions, hog1 and pbs2 mutant strains display different alterations, suc...

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The Candida albicans histidine kinase Chk1p: Signaling and cell wall mannan

Williams

Lowman

et al. 2009

Fungal Genetics and Biology

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Several published functions associated with the CHK1 histidine kinase of Candida albicans resemble those of the MAPK Cek1p and its cognate receptor Sho1p (SSU81). To explore this further, we have compared mutants lacking the proteins mentioned above and have constructed a double sho1/ chk1Δ null mutant to determine relationships among these proteins. We observed that the sensitivity to Congo red (CR), calcofluor white (CW), as well as clumping of cells, was slightly increased in the double mutant compared to the single chk1Δ or sho1Δ mutants. However, Cek1p phosphorylation via Sho1p, which occurs during log phase growth in the presence or absence of CR in Wt cells, does not require Chk1p. These data suggest that Chk1p and Sho1p are components of parallel but independent signal pathways. In addition, bulk mannan of strains was analyzed by GPC/MS and NMR. Compared to Wt and a CHK1 gene-reconstituted strain (CHK23) that contained, high, intermediate and low Mw mannan species, we found that the mannan of strains CHK21 (chk1Δ null), the cek1Δ null, and the double mutant consisted only of low Mw mannan. The sho1Δ null mutant only demonstrated a reduced intermediate type of mannan. Alcian blue binding was lower in cek1Δ, chk1Δ, and the double sho1/chk1Δ null mutant lacking high and intermediate Mw mannan than in the sho1Δ null which had a partial loss of intermediate Mw mannan only. We conclude that the Chk1p HK is part of a functionally similar but parallel pathway to the Sho1p-Cek1p pathway that confers resistance to the cell wall inhibitors CR and CW. However, a functional relationship in mannan biosynthesis of Chk1p and Cek1p exists that only partially requires Sho1p.

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The role of the histidine kinase [) gene in the regulation of cell wall mannan and glucan biosynthesis

Cited by 21 publications

References 38 publications

Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene

Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene

The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans

The Candida albicans histidine kinase Chk1p: Signaling and cell wall mannan

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