The HOG Pathway Is Critical for the Colonization of the Mouse Gastrointestinal Tract by Candida albicans

Abstract

The opportunistic pathogen Candida albicans is a frequent inhabitant of the human gastrointestinal tract where it usually behaves as a harmless commensal. In this particular niche, it needs to adapt to the different micro environments that challenge its survival within the host. In order to determine those factors involved in gut adaptation, we have used a gastrointestinal model of colonization in mouse to trace the behaviour of fungal cells. We have developed a genetic labelling system based on the complementary spectral properties of the fluorescent proteins GFP and a new C. albicans codon-adapted RFP (dTOM2) that allow a precise quantification of the fungal population in the gut via standard in vitro cultures or flow cytometry. This methodology has allowed us to determine the role of the three MAP kinase pathways of C. albicans (mediated by the MAPK Mkc1, Cek1 or Hog1) in mouse gut colonization via competitive assays with MAPK pathway mutants and their isogenic wild type strain. This approach reveals the signalling through HOG pathway as a critical factor influencing the establishment of C. albicans in the mouse gut. Less pronounced effects for mkc1 or cek1 mutants were found, only evident after 2–3 weeks of colonization. We have also seen that hog1 mutants is defective in adhesion to the gut mucosa and sensitive to bile salts. Finally, we have developed a genetic strategy for the in vivo excision (tetracycline-dependent) of any specific gene during the course of colonization in this particular niche, allowing the analysis of its role during gut colonization.

Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

“…Although our study focused on the oral mucosa, based on the oral administration of the microbes there was potential for the cocolonization of the GI tract to occur as well. C. albicans and S. aureus have both been shown to be able to colonize the GI tract (Acton et al, 2009;Prieto et al, 2014), and GI candidiasis can occur in immunocompromised individuals, although it is much less common than oral candidiasis (Vazquez & Sobel, 2002). Although our current study failed to examine this potential route of invasion, we feel that based on the requirement that Als3p be present in order to produce systemic S. aureus bacteraemia, any dissemination occurring through the gut mucosa is likely to be occurring through the same proposed model of Als3p binding and hitchhiking.…”

Candida Survival Strategies

“…Stress-responsive pathways and their downstream targets were shown to be necessary for colonization but also for virulence of C. albicans (Alonso- Monge et al, 1999;Csank et al, 1998;Diez-Orejas et al, 1997;Prieto, Roman, Correia, & Pla, 2014). Important adaptation mechanisms and recent insights in survival strategies under various stress conditions have recently been reviewed (Brown, Budge, et al,2014;Brown, Haynes, Gow, & Quinn, 2012;Brown, Haynes, & Quinn, 2009).…”

“…In addition, coinfections are not uncommon: 4e8% of all Candidaassociated bloodstream infections involve more than one Candida spp. and it was estimated that >20% of C. albicans bloodstream infections also involve bacteria (Bouza et al, 2013;Klotz, Chasin, et al, 2007;Nace, Horn, & Neofytos, 2009;Pulimood et al, 2002). The most often coisolated species are Staphylococcus epidermidis, Enterococcus spp.…”

“…A summary of important survival mechanisms can be found in Figure 2. Furthermore, because of the emergence of medical device associated and polymicrobial infections in recent years (Bonhomme & d'Enfert, 2013;Bouza et al, 2013;Harriott & Noverr, 2011;Klotz, Chasin, Powell, Gaur, & Lipke, 2007;Morales & Hogan, 2010;Pulimood, Ganesan, Alangaden, & Chandrasekar, 2002;Ramage, Mowat, Jones, Williams, & LopezRibot, 2009;Shirtliff, Peters, & Jabra-Rizk, 2009), part of this chapter will focus on biofilms as multicellular communities and their role as " safe haven" for the yeast. We will review the importance of intercellular and interspecies signaling mechanisms for C. albicans in order to build and maintain these multicellular structures.…”

The Cek1‑mediated MAP kinase pathway regulates exposure of α‑1,2 and β‑1,2‑mannosides in the cell wall ofCandida albicansmodulating immune recognition

“…94 Cells were grown at 37 C in YEPD medium (1% yeast extract, 2% peptone and 2% dextrose) unless otherwise stated. The generation times for the indicated strains growing at 37 C in rich YEPD medium were the following: 78 min (CAF2), 82 min (cek1), 88 min (mkc1), 88 min (hog1) and 83 min (hst7).…”