Increases in SLT2 Expression and Chitin Content Are Associated with Incomplete Killing of Candida glabrata by Caspofungin

Both calcineurin and PKC signaling have been implicated in echinocandin resistance in C. glabrata.

“Both calcineurin and PKC signaling have been implicated in echinocandin resistance in C. glabrata [93,103,106].”

CgSLT2 has previously been reported to be transcriptionally up-regulated in response to the echinocandin drug caspofungin.

“CgSLT2 has previously been reported to be transcriptionally up-regulated in response to an echinocandin drug, caspofungin (51).”

Induction of the CWI pathway in Candida species, including C. glabrata, has been linked to increased production of chitin, potentially compensating for loss of beta-1,3-glucans.

“Induction of the CWI pathway in Candida species (Stevens et al., 2006; Walker et al., 2013), including C. glabrata (Cota et al., 2008), has been linked to increased production of other cell wall components, such as chitin, potentially compensating for the loss of beta-1,3-glucans.”

Targeting the CWI pathway through deletion of PKC1 or activated MAP kinases induces echinocandin hypersensitivity, while increased activation of the pathway reduces susceptibility of C. glabrata to echinocandins.

“Targeting the CWI pathway through deletion of PKC1 or activated MAP kinases (e.g., CgSLT2) induces echinocandin hypersensitivity; while conversely, an increased activation of the pathway, such as through over-expression of CgSLT2, reduces susceptibility (increases tolerance) of C. glabrata to echinocandins (Cota et al., 2008; Miyazaki et al., 2010a; Schwarzmuller et al., 2014).”