Cited by 237Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

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Patients with Long-Term Oral Carriage Harbor High-Persister Mutants of Candida albicans

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LaFleur, Michael D., Qi, Qingguo, Lewis, Kim·2010·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.00860-09PMC PMC2798516

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Abstract

Fungal biofilms produce a small number of persister cells which can tolerate high concentrations of fungicidal agents. Persisters form upon attachment to a surface, an important step in the pathogenesis of Candida strains. The periodic application of antimicrobial agents may select for strains with increased levels of persister cells. In order to test this possibility, 150 isolates of Candida albicans and C. glabrata were obtained from cancer patients who were at high risk for the development of oral candidiasis and who had been treated with topical chlorhexidine once a day. Persister levels were measured by exposing biofilms growing in the wells of microtiter plates to high concentrations of amphotericin B and plating for survivors. The persister levels of the isolates varied from 0.2 to 9%, and strains isolated from patients with long-term carriage had high levels of persisters. High-persister strains were isolated from every patient with Candida carriage of more than 8 consecutive weeks but from no patients with transient carriage. All of the high-persister isolates had an amphotericin B MIC that was the same as that for the wild type, indicating that these strains were drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of high-persister strains also showed an increased tolerance to chlorhexidine and had the same MIC for this antimicrobial as the wild type. This study suggests that persister cells are clinically relevant, and antimicrobial therapy selects for high-persister strains in vivo. The drug tolerance of persisters may be a critical but overlooked component responsible for antimicrobial drug failure and relapsing infections.

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Authors: LaFleur, M. D., Qi, Q., & Lewis, K.
Affiliations: Northeastern University (US)
Antimicrobial Discovery Center and Department of Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115
Corresponding author: Lewis, Kim
ORCID: Lewis, Kim
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2010-01
Volume: 54
Issue: 1
Pages: 39-44
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.00860-09
PMC: PMC2798516
OpenAlex: W2115712103
Cited by: 237
References: 32
Citations by year: 2026: 4 · 2025: 7 · 2024: 14 · 2023: 9 · 2022: 16 · 2021: 21 · 2020: 18 · 2019: 16 · 2018: 9 · 2017: 15 · 2016: 21 · 2015: 24 · 2014: 12 · 2013: 24 · 2012: 17
FWCI: 6.21
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (30400498)
National Institute of General Medical Sciences (R01GM061162)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords: Candida albicans, Candida glabrata, persister cells, fungal biofilms, oral candidiasis, drug tolerance, antimicrobial selection, cancer patients, infection relapse
MeSH terms: Adult, Aged, Candida albicans, Candidiasis, Carrier State, Chlorhexidine, Dose-Response Relationship, Drug, Female, Genes, Fungal, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mouth, Mouthwashes, Mutation, Neoplasms, Biofilms, Young Adult

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Patients with Long-Term Oral Carriage Harbor High-Persister Mutants of Candida albicans

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