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Cellular and Molecular Life Sciences

, Volume 72, Issue 12, pp 2261–2287 | Cite as

Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies

  • Elizabeth J. Polvi
  • Xinliu Li
  • Teresa R. O’Meara
  • Michelle D. Leach
  • Leah E. CowenEmail author
Review

Abstract

Life-threatening invasive fungal infections are becoming increasingly common, at least in part due to the prevalence of medical interventions resulting in immunosuppression. Opportunistic fungal pathogens of humans exploit hosts that are immunocompromised, whether by immunosuppression or genetic predisposition, with infections originating from either commensal or environmental sources. Fungal pathogens are armed with an arsenal of traits that promote pathogenesis, including the ability to survive host physiological conditions and to switch between different morphological states. Despite the profound impact of fungal pathogens on human health worldwide, diagnostic strategies remain crude and treatment options are limited, with resistance to antifungal drugs on the rise. This review will focus on the global burden of fungal infections, the reservoirs of these pathogens, the traits of opportunistic yeast that lead to pathogenesis, host genetic susceptibilities, and the challenges that must be overcome to combat antifungal drug resistance and improve clinical outcome.

Keywords

Opportunistic Fungi Yeast Pathogen Candida Cryptococcus Histoplasma Pneumocystis 

Abbreviations

ABPA

Allergic bronchopulmonary aspergillosis

APECED

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

cAMP

Cyclic AMP

CDC

Centers for Disease Control and Prevention

CGD

Chronic granulomatous disease

CLR

C-type lectin receptors

CMC

Chronic mucocutaneous candidiasis

CNS

Central nervous system

COPD

Chronic obstructive pulmonary disease

CRP

C-reactive protein

ECM

Extracellular matrix

GUT

Gastrointestinally induced transition

GXM

Glucuronoxylomannan

GXMGal

Glucuronoxylomannogalactan

HAART

Highly active antiretroviral therapies

HIES

Hyper-IgE syndrome

HSP

Heat shock protein

IFN-γ

Interferon-γ

IL

Interleukin

IRIS

Immune reconstitution inflammatory syndrome

MPO

Myeloperoxidase

MR

Mannose receptors

NF-κB

Nuclear factor-κB

NO

Nitric oxide

PAMP

Pathogen-associated molecular pattern

PCP

Pneumocystis pneumonia

PKA

Protein kinase A

PKC

Protein kinase C

PRR

Pattern recognition receptors

SAP

Secreted aspartyl proteinase

TGF-β

Transforming growth factor-β

TLR

Toll-like receptors

TNF-α

Tumor necrosis factor-α

Treg cell

Regulatory T cell

VVC

Vulvovaginal candidiasis

Notes

Acknowledgments

We thank the J. Andrew Alspaugh and Chad Rappleye labs for images and Cowen lab members for helpful discussions. EJP is supported by a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best CGS Doctoral Award, XL by a University of Toronto Fellowship, MDL by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), and LEC by a Ministry of Research and Innovation Early Researcher Award, Canada Research Chair in Microbial Genomics and Infectious Disease, Natural Sciences and Engineering Research Council Discovery Grant #355965, and by Canadian Institutes of Health Research Grants MOP-86452 and MOP-119520.

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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Elizabeth J. Polvi
    • 1
  • Xinliu Li
    • 1
  • Teresa R. O’Meara
    • 1
  • Michelle D. Leach
    • 1
    • 2
  • Leah E. Cowen
    • 1
    Email author
  1. 1.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  2. 2.Aberdeen Fungal Group, Institute of Medical Sciences, School of Medical SciencesUniversity of AberdeenAberdeenUK

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