Fluconazole-Resistant Candida auris Is Susceptible to Salivary Histatin 5 Killing and to Intrinsic Host Defenses

Antimicrobial Agents and Chemotherapy
Ruvini U PathiranaM Edgerton

Abstract

Candida auris is a newly identified species causing invasive candidemia and candidiasis. It has broad multidrug resistance (MDR) not observed for other pathogenic Candida species. Histatin 5 (Hst 5) is a well-studied salivary cationic peptide with significant antifungal activity against Candida albicans and is an attractive candidate for treating MDR fungi, since antimicrobial peptides induce minimal drug resistance. We investigated the susceptibility of C. auris to Hst 5 and neutrophils, two first-line innate defenses in the human host. The majority of C. auris clinical isolates, including fluconazole-resistant strains, were highly sensitive to Hst 5: 55 to 90% of cells were killed by use of 7.5 μM Hst 5. Hst 5 was translocated to the cytosol and vacuole in C. auris cells; such translocation is required for the killing of C. albicans by Hst 5. The inverse relationship between fluconazole resistance and Hst 5 killing suggests different cellular targets for Hst 5 than for fluconazole. C. auris showed higher tolerance to oxidative stress than C. albicans, and higher survival within neutrophils, which correlated with resistance to oxidative stress in vitro Thus, resistance to reactive oxygen species (ROS) is likely one, though not...Continue Reading

References

Jan 1, 1991·Journal of Medical and Veterinary Mycology : Bi-monthly Publication of the International Society for Human and Animal Mycology·I B GargeyaD G Ahearn
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Deirdre H FitzgeraldBrian C O'Connell
Aug 13, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Hilmar WisplinghoffMichael B Edmond
Feb 20, 2007·Mycoses·Roland WakiećSławomir Milewski
Oct 26, 2007·Molecular Biology of the Cell·Matthew J BrauerDavid Botstein
Nov 30, 2010·Current Medicinal Chemistry·Giovanna BatoniMario Campa
Jul 1, 2011·Journal of Clinical Microbiology·Wee Gyo LeeHee-Chang Jang
Oct 22, 2011·International Journal of Molecular Sciences·Seong-Cheol ParkKyung-Soo Hahm
Mar 15, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Barbara D AlexanderMichael A Pfaller
Sep 21, 2013·Emerging Infectious Diseases·Anuradha ChowdharyJacques F Meis
Mar 29, 2014·The New England Journal of Medicine·Shelley S MagillUNKNOWN Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team
Jun 22, 2014·Eukaryotic Cell·Sumant Puri, Mira Edgerton
Jun 26, 2014·Emerging Infectious Diseases·Rindidzani E MagoboNelesh P Govender
Sep 9, 2015·BMC Genomics·Sharanya ChatterjeeUtpal S Tatu
Mar 26, 2016·Frontiers in Medicine·Dominique Sanglard
Dec 19, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Shawn R LockhartAnastasia P Litvintseva
Dec 19, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Cornelius J Clancy, M Hong Nguyen
Dec 29, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S VallabhaneniT M Chiller
Jan 19, 2017·Emerging Infectious Diseases·Ronen Ben-AmiTalya Finn
Jan 19, 2017·Emerging Infectious Diseases·Leighann SherryRiina Rautemaa-Richardson
Mar 7, 2017·Frontiers in Cellular and Infection Microbiology·Han DuMira Edgerton
May 19, 2017·MMWR. Morbidity and Mortality Weekly Report·Sharon TsayBrendan R Jackson
Mar 6, 2018·Clinical Microbiology Newsletter·Shawn R LockhartRory M Welsh

❮ Previous
Next ❯

Citations

Sep 27, 2018·Infection and Immunity·Ornella SalvatoriMira Edgerton
Feb 6, 2019·Antimicrobial Agents and Chemotherapy·Jeffrey M RybakP David Rogers
Apr 9, 2019·PLoS Pathogens·Jeniel E Nett
Jun 22, 2019·The Journal of Antimicrobial Chemotherapy·Sebastian WursterDimitrios P Kontoyiannis
Apr 17, 2020·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Amira ElBaradei
Aug 28, 2020·Frontiers in Cellular and Infection Microbiology·Rodnei Dennis RossoniEleftherios Mylonakis
Oct 23, 2020·PLoS Pathogens·Han DuGuanghua Huang
May 1, 2021·International Journal of Molecular Sciences·Lucia ČernákováCélia F Rodrigues
Apr 30, 2021·Frontiers in Cell and Developmental Biology·Caroline StruyfsKarin Thevissen
Jun 29, 2021·Expert Review of Clinical Pharmacology·Daniele R GiacobbeMatteo Bassetti

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.