Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

Abstract

Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.

The Ndr/LATS Kinase Cbk1 Regulates a Specific Subset of Ace2 Functions and Suppresses the Hypha-to-Yeast Transition in Candida albicans

“…As a component of the human mycobiome, C. albicans primarily colonizes the human oral cavity, gastrointestinal tract, and urogenital tract ( 2 ). Accordingly, it is well adapted to niches that differ greatly in their environmental characteristics ( 3 ). Regardless of the specific niche or site of infection, however, the ability of C. albicans to cause disease has been closely linked to its ability to undergo morphogenic transitions to either pseudohyphae or true hyphae ( 4 ).…”

“…environmental characteristics (3). Regardless of the specific niche or site of infection, however, the ability of C. albicans to cause disease has been closely linked to its ability to undergo morphogenic transitions to either pseudohyphae or true hyphae (4).…”

Recognition of Candida albicans and Role of Innate Type 17 Immunity in Oral Candidiasis

“…In addition, C. albicans can escape from the host's defense mechanisms in multiple ways. Besides genetically determined resistance, C. albicans can form rigid biofilms where cells become phenotypically resistant to antimicrobials and the immune system [142][143][144][145]. It appears that we still have a long way to go to understand how the immune system overcomes biofilm-associated resistance.…”

<p>Optimized Production of the Allylamine Antifungal “Terbinafine” by <em>Lysinibacillus</em> Isolate MK212927 Using Response Surface Methodology</p>

“…to form drug-resistant biofilm is a driving factor for fungal pathogenicity. 7 Indeed, there is an increased need for new drugs to treat fungal diseases in humans.…”