title: Candida albicans Amphotericin B-Tolerant Persister Formation is Closely Related to Surface Adhesion.
abstract: Candida albicans persisters have so far been observed only in biofilm environment; the biofilm element(s) that trigger(s) persister formation are still unknown. In this study, we tried to further elucidate the possible relationship between C. albicans persisters and the early phases of biofilm formation, especially the surface adhesion phase. Three C. albicans strains were surveyed for the formation of persisters. We tested C. albicans persister formation dynamically at different time points during the process of adhesion and biofilm formation. The number of persister cells was determined based on an assessment of cell viability after amphotericin B treatment and colony-forming unit assay. None of the planktonic cultures contained persisters. Immediately following adhesion of C. albicans cells to the surface, persister cells emerged and the proportion of persisters reached a peak of 0.2-0.69 % in approximately 2-h biofilm. As the biofilm matured, the proportion of persisters decreased and was only 0.01-0.02 % by 24 h, while the number of persisters remained stable with no significant change. Persisters were not detected in the absence of an attachment surface which was pre-coated. Persisters were also absent in biofilms that were scraped to disrupt surface adhesion prior to amphotericin B treatment. These results indicate that C. albicans antifungal-tolerant persisters are produced mainly in surface adhesion phase and surface adhesion is required for the emergence and maintenance of C. albicans persisters.
authors.affiliation: Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong, China.|Shandong Provincial Key Laboratory of Oral Biomedicine, 44-1 Wenhuaxi Road, Jinan, Shandong, China.|School of Stomatology, Shandong University, 44-1 Wenhuaxi Road, Jinan, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Qianfoshan Hospital Shandong Province, 16766 Jingshi Road, Jinan, Shandong, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, 44-1 Wenhuaxi Road, Jinan, Shandong, China.|School of Stomatology, Shandong University, 44-1 Wenhuaxi Road, Jinan, Shandong, China.
authors.forename: Haoyue
authors.initials: H
authors.lastname: Chu
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, 44-1 Wenhuaxi Road, Jinan, Shandong, China.|School of Stomatology, Shandong University, 44-1 Wenhuaxi Road, Jinan, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, 44-1 Wenhuaxi Road, Jinan, Shandong, China. gjiang@sdu.edu.cn.|School of Stomatology, Shandong University, 44-1 Wenhuaxi Road, Jinan, Shandong, China. gjiang@sdu.edu.cn.
authors.forename: Guangshui
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, 44-1 Wenhuaxi Road, Jinan, Shandong, China. qqg@sdu.edu.cn.|School of Stomatology, Shandong University, 44-1 Wenhuaxi Road, Jinan, Shandong, China. qqg@sdu.edu.cn.|Cheeloo Health Science Center, Shandong University, Jinan, 250012, Shandong, China. qqg@sdu.edu.cn.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Qi
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology*; D002448:Cell Adhesion; D015169:Colony Count, Microbial; D004361:Drug Tolerance
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B
keywords: Adhesion; Biofilm; Candida albicans; Persisters