Mechanisms of Drug Resistance in Fungi and Their Significance in Biofilms - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 44

While most fungi are nonpathogenic, there are a large number of them, belonging to
almost every phylum, which are pathogenic to humans, animals, and plants
(Heitman 2011 ). Fungi as pathogens are involved in many afflictions, which
range from superficial to life-threatening disseminated infectious diseases (Odds
1988 ). Human fungal pathogens are mostly opportunistic, implying that a success-
ful infection depends upon the status of the immune defense system of the host.
Advancement in preventive measures like immune suppression during organ trans-
plantations and life threatening diseases like AIDS help opportunistic fungi find
suitable hosts in which to thrive. These common opportunistic fungal species are
either Candida species like Candida alibicans, C. glabrata, C. tropicals,
C. paropsilosis, C. dubliniensis, C. guilliermondii, C. krusei, C. lusitaniae ,or
non- Candida fungi like Aspergillus fumigatus, Cryptococcus neoformans,
Histoplasma caspulatum, Microsporum canis, Paracoccidioides brasiliensis , Pen-
icillium marneffei, Blastomycoides dermatitidis , and Pneumocystis sp. (Sanglard
et al. 2009 ; Heitman 2011 ; Gow et al. 2011 ).
Candida species are one of the most prevalent causes of systemic fungal
infections in humans. Among Candida species, C. albicans is well adapted to thrive
in most of the organs and niches of humans, making it the most successful human
fungal pathogen. Not surprisingly, C. albicans alone contributes to 50-60 % of
Candida infections followed by non-albicans species, which mostly include
C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei (Silva et al. 2011 ; Prasad
et al. 2012 ) . Infections due to uncommon fungi and pathogenic molds like
Trichosporon species, Fusarium , and Scedosporium species have also been
reported. Trichosporon species causes diseases similar to hepatic candidiasis
while Fusarium and Scedosporium species are commonly found in hospital-
acquired fungal infections and show high levels of resistance to amphotericin B
(AMB) and azoles (Fridkin 2005 ; Bonatti et al. 2007 ).
Many opportunistic pathogens pose an additional threat because of their ability
to acquire tolerance to antifungal treatments leading to the development of
multidrug resistance (MDR). For this, fungi have developed several strategies to
tolerate most of the mainstream antifungal drugs like azoles, polyenes, allyamine,
and echinocandins. Notably, many of the mechanisms of MDR are also common to
multidrug-resistant cancer or bacterial cells and have been discussed and reviewed
in recent years (Sanglard and Odds 2002 ; Prasad and Kapoor 2005 ; Sanglard
et al. 2009 ; Cannon et al. 2009 ; Morschh¨user 2010 ; Prasad and Goffeau 2012 ).
In this chapter we provide a snapshot of the current MDR environment and discuss
some of the strategies of azole resistance adopted by fungal cells.
2 MDR Strategies
The limited availability of antifungals is a major impediment for the effective
treatment of fungal infections (Ghannoum and Rice 1999 ). This is further
compounded by the fact that the generation of newer antifungals has lagged behind,