A New Determinant of Candida glabrata Virulence: The Acetate Exporter CgDtr1.

Daniela Romão,Rui Santos,Miguel C Teixeira,Pedro Pais,Mafalda Cavalheiro,Dalila Mil-Homens,Hiroji Chibana,Arsénio M Fialho,Azusa Takahashi-Nakaguchi,Catarina Costa

doi:10.3389/fcimb.2017.00473

Abstract

Persistence and virulence of Candida glabrata infections are multifactorial phenomena, whose understanding is crucial to design more suitable therapeutic strategies. In this study, the putative multidrug transporter CgDtr1, encoded by ORF CAGL0M06281g, is identified as a determinant of C. glabrata virulence in the infection model Galleria mellonella. CgDTR1 deletion is shown to decrease the ability to kill G. mellonella larvae by decreasing C. glabrata ability to proliferate in G. mellonella hemolymph, and to tolerate the action of hemocytes. The possible role of CgDtr1 in the resistance to several stress factors that underlie death induced by phagocytosis was assessed. CgDTR1 was found to confer resistance to oxidative and acetic acid stress. Consistently, CgDtr1 was found to be a plasma membrane acetic acid exporter, relieving the stress induced upon C. glabrata cells within hemocytes, and thus enabling increased proliferation and virulence against G. mellonella larvae.

Highlights

Infections caused by Candida species are recognized as the 4th most common cause of nosocomial infections (Wisplinghoff et al, 2004)
Given its predicted function as a multidrug resistance transporter, together with the results described above, it appeared reasonable to hypothesize that the role of CgDtr1 in C. glabrata proliferation within G. mellonella hemocytes is related to defending the yeast cell against the stress factors encountered within hemocytic cells
The multidrug transporter CgDtr1 was shown to play a role in C. glabrata pathogenesis, protecting these cells from stress agents present in macrophagic cells

Summary

Introduction

Infections caused by Candida species are recognized as the 4th most common cause of nosocomial infections (Wisplinghoff et al, 2004). Candida glabrata is the second most common cause of invasive candidiasis, with an estimated death rate of 40–50% (Tscherner et al, 2011) Infections caused by this pathogenic yeast have increased worldwide (Rodrigues et al, 2014; Yapar, 2014), which is likely due to the relatively high prevalence of antifungal drug resistance among C. glabrata clinical isolates (Tscherner et al, 2011; Pfaller et al, 2014). It may be the result of its ability to survive under stress conditions, such as those imposed by the host immune system (Pfaller et al, 2014). Crucial to fully understand these pathogenesis-related phenomena in order to design better ways to prevent and control superficial and invasive candidiasis caused by C. glabrata

Methods

Results

Conclusion