Epidemiological status and drug resistance survey of protothecosis in China from 2015 to 2025

doi:10.16150/j.1671-2870.2026.03.006

Abstract

Abstract:

Objective Prototheca is a unicellular microalga belonging to the family Chlorellaceae that has lost its chlorophyll and the ability to perform photosynthesis, exhibiting biological characteristics intermediate between algae and fungi. Protothecosis is predominantly an exogenous infection, with pathogens commonly invading through damaged skin or mucous membranes via contact with contaminated soil, water, or organic matter. Clinical manifestations primarily include cutaneous and subcutaneous infections and olecranon bursitis. This study investigates the epidemiological characteristics and antimicrobial susceptibility distribution of protothecosis in China from 2015 to 2025, aiming to bridge the gap in domestic epidemiological data and clinical management guidelines of protothecosis, and to provide a scientific basis for its clinical diagnosis, treatment, and prevention strategies. Methods A total of 84 clinical Prototheca isolates collected by the Protothecosis Science Popularization and Monitoring Consortium (PSPMC) between 2015 and 2025 were retrospectively analyzed. In vitro susceptibility testing was performed for all isolates using the broth microdilution method. The tested agents included five azoles, three echinocandins, 5-flucytosine, and amphotericin B. Additionally, CYTB gene sequencing was conducted, followed by phylogenetic analysis. Results Among the isolates obtained from patients with protothecosis in China between 2015 and 2025, Prototheca wickerhamii was the predominant species (79.8%), followed by Prototheca bovis (11.9%). The highest number of isolates was found in East China (45.2%). The infections predominantly affected middle-aged and elderly individuals, with 82.1% of patients aged between 41 and 80 years. Skin tissue was the most common isolation source, accounting for 59.5% of all clinical isolates. Non-cutaneous sources included cerebrospinal fluid, blood, ascitic fluid, and bronchoalveolar lavage fluid. Azole antifungal agents, such as itraconazole, posaconazole, and voriconazole, demonstrated strong antimicrobial activity against Prototheca, with the minimum inhibitory concentration (MIC) required to inhibit 50% of isolates (MIC₅₀) being 1.000 μg/mL. Isavuconazole exhibited superior activity, with MICs ranging from 0.015 to 1.000 μg/mL. Amphotericin B also showed strong antimicrobial activity (MIC₅₀ = 0.500 μg/mL). Conversely, fluconazole, 5-flucytosine, and echinocandins showed no significant antimicrobial activity against Prototheca. The antimicrobial activity of isavuconazole against P. wickerhamii was significantly higher than against P. bovis and Prototheca zopfii. Phylogenetic analysis indicated that P. wickerhamii constituted the major evolutionary clade with a highly complex structure, suggesting significant intraspecific genetic heterogeneity. Conclusions Prototheca wickerhamii is the predominant species among isolates obtained from patients with protothecosis in China. The infected population mainly consists of middle-aged and elderly individuals. While skin is the main site of infection, non-cutaneous sites are widely distributed. Amphotericin B and isavuconazole demonstrate strong in vitro antimicrobial activity against these clinical Prototheca isolates, although susceptibility varies among different species.

Key words: Prototheca, Protothecosis, Epidemiological characteristics, Antimicrobial susceptibility, Minimum inhibitory concentration

CLC Number:

R446
R519.5

WANG Lili, GUO Jian. Epidemiological status and drug resistance survey of protothecosis in China from 2015 to 2025[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(03): 308-314.

Figures/Tables 5

Table 1

Table 2

Figure 1

Table 3

Figure 2

References 18

[1]	THIELE D, BERGMANN A. Protothecosis in human medicine[J]. Int J Hyg Environ Health, 2002, 204(5/6):297-302. doi: 10.1078/1438-4639-00105 URL
[2]	LASS-FLÖRL C, MAYR A. Human protothecosis[J]. Clin Microbiol Rev, 2007, 20(2):230-242. doi: 10.1128/CMR.00032-06 URL
[3]	TODD J R, KING J W, OBERLE A, et al. Protothecosis: Report of a case with 20-year follow-up, and review of previously published cases[J]. Med Mycol, 2012, 50(7):673-689. doi: 10.3109/13693786.2012.677862 pmid: 22571772
[4]	TSENG I L, LIU W T. Cutaneous protothecosis[J]. Acad Dermatol Venereol, 2026, 40(5):908-909. doi: 10.1111/jdv.v40.5 URL
[5]	INOUE M, MIYASHITA A, NOGUCHI H, et al. Case report of cutaneous protothecosis caused by Prototheca wickerhamii designated as genotype 2 and current status of human protothecosis in Japan[J]. J Dermatol, 2018, 45(1):67-71. doi: 10.1111/jde.2018.45.issue-1 URL
[6]	MATHEW L G, PULIMOOD S, THOMAS M, et al. Disseminated protothecosis[J]. Indian J Pediatr, 2010, 77(2):198-199. doi: 10.1007/s12098-009-0251-6 pmid: 19936664
[7]	JAGIELSKI T, GAWOR J, BAKUŁA Z, et al. cytbas a new genetic marker for differentiation of Prototheca Species[J]. J Clin Microbiol, 2018, 56(10):e00584-e00518.
[8]	WANG X, RAN Y, JIA S, et al. Human disseminated protothecosis: The skin is the “window”?[J]. Front Immunol, 2022,13:880196.
[9]	SETHURAMAN N, RAO P, RAMANATHAN Y, et al. Disseminated protothecosis caused by Prototheca zopfii in a liver transplant recipient[J]. J Global Infect Dis, 2018, 10(4):228. doi: 10.4103/jgid.jgid_55_17 URL
[10]	JAGIELSKI T, ISKRA M, BAKUŁA Z, et al. Occurrence ofProtothecaMicroalgae in aquatic ecosystems with a description of three new species, Prototheca fontanea, Prototheca lentecrescens, and Prototheca vistulensis[J]. Appl Environ Microbiol, 2022, 88(22):e01092-e01022.
[11]	MAYORGA J, BARBA-GÓMEZ J F, VERDUZCO-MARTÍNEZ A P, et al. Protothecosis[J]. Clin Dermatol, 2012, 30(4):432-436. doi: 10.1016/j.clindermatol.2011.09.016 pmid: 22682193
[12]	PROSKURNICKA A, ŻUPNIK K, BAKUŁA Z, et al. Drug susceptibility profiling of Prototheca Species isolated from cases of human protothecosis[J]. Antimicrob Agents Chemother, 2023, 67(4):e01627-e01622.
[13]	JAGIELSKI T, BAKUŁA Z, DI MAURO S, et al. A comparative study of the in vitro activity of iodopropynyl butylcarbamate and amphotericin B against Prototheca spp. isolates from European dairy herds[J]. J Dairy Sci, 2017, 100(9):7435-7445. doi: 10.3168/jds.2017-12597 URL
[14]	TORTORANO A M, PRIGITANO A, DHO G, et al. In vitro activity of conventional antifungal drugs and natural essences against the yeast-like Alga Prototheca[J]. J Antimicrob Chemother, 2008, 61(6):1312-1314. doi: 10.1093/jac/dkn107 pmid: 18339634
[15]	MACESIC N, FLEMING S, KIDD S, et al. Protothecosis in hematopoietic stem cell transplantation: Case report and review of previous cases[J]. Transpl Infect Dis, 2014, 16(3):490-495. doi: 10.1111/tid.12223 pmid: 24797402
[16]	TUOHUTI P, CHEN Y, ZHAO A, et al. Isavuconazole for the treatment of invasive fungal disease in hematology patients: A real-world retrospective study on efficacy and safety[J]. Microorganisms, 2025, 13(12):2677. doi: 10.3390/microorganisms13122677 URL
[17]	ÁLVAREZ-PÉREZ S, ANEGA B, DÍAZ-DE-TUESTA J A, et al. Susceptibility testing of Prototheca bovis isolates from cases of bovine mastitis using the CLSI reference broth microdilution method and the Sensititre YeastOne colorimetric panel[J]. Med Mycol, 2021, 59(12):1257-1261. doi: 10.1093/mmy/myab063 URL
[18]	MASUDA M, JAGIELSKI T, DANESI P, et al. Protothecosis in dogs and cats: New research directions[J]. Mycopathologia, 2021, 186(1):143-152. doi: 10.1007/s11046-020-00508-y

Category	Subcategory	Number (%)
Age, years	0-20	3 (3.6%)
	21-40	5 (6.0%)
	41-60	29 (34.5%)
	61-80	40 (47.6%)
	>81	7 (8.3%)
Gender	Male	43 (51.2%)
	Female	41 (48.8%)
Species	Prototheca wickerhamii	67 (79.8%)
	Prototheca bovis	10 (11.9%)
	Prototheca zopfii	5 (6.0%)
	Prototheca ciferrii	1 (1.2%)
	Prototheca miyajii	1 (1.2%)
Site of isolation	Skin tissue	50 (59.5%)
	Feces	9 (10.7%)
	Ascitic fluid	4 (4.8%)
	Cerebrospinal fluid	3 (3.6%)
	Blood	5 (6.0%)
	Sputum	3 (3.6%)
	Bronchoalveolar lavage fluid	3 (3.6%)
	Wound secretion	3 (3.6%)
	Pus	3 (3.6%)
	Joint fluid	1 (1.2%)

Antibiotics	All (n=84)			Skin tissue (n=50)			Non-skin tissue (n=34)
Antibiotics	MIC range (µg/mL)	MIC₅₀ (µg/mL)	MIC₉₀ (µg/mL)	MIC range (µg/mL)	MIC₅₀ (µg/mL)	MIC₉₀ (µg/mL)	MIC range (µg/mL)	MIC₅₀ (µg/mL)	MIC₉₀ (µg/mL)
Isavuconazole	0.015-1.000	0.060	0.250	0.015-0.500	0.060	0.120	0.015-1.00	0.120	0.500
Itraconazole	0.250-16.000	1.000	2.000	0.500-16.000	1.000	2.000	0.250-16.000	1.000	16.000
Posaconazole	0.500-8.000	1.000	2.000	0.500-4.000	1.000	2.000	0.500-8.000	1.000	2.000
Voriconazole	0.500-8.000	1.000	4.000	0.500-4.000	1.000	2.000	0.500-8.000	2.000	4.000
Amphotericin B	0.250-1.000	0.500	0.500	0.500-1.000	0.500	0.500	0.250-1.000	0.500	1.000
Anidulafungin	8.000-8.000	8.000	8.000	8.000-8.000	8.000	8.000	8.000-8.000	8.000	8.000
Caspofungin	4.000-4.000	4.000	4.000	4.000-4.000	4.000	4.000	4.000-4.000	4.000	4.000
Micafungin	8.00-8.000	8.000	8.000	8.000-8.000	8.000	8.000	8.000-8.000	8.000	8.000
Fluconazole	128.000-256.000	256.000	256.000	128.000-256.000	256.000	256.000	256.000-256.000	256.000	256.000
5-Fluorocytosine	32.000-32.000	32.000	32.000	32.000-32.000	32.000	32.000	32.000-32.000	32.000	32.000

Species	Minimum inhibitory concentration range (µg/mL)
Species	ISA	ITR	POS	VOR	AMB	ANI	CAS	MIC	FLU	5-FC
P. wickerhamii（n=67）	0.015-0.500	0.500-16.000	0.500-4.000	0.500-4.000	0.250-1.000	8.000	4.000	8.000	128.000-256.000	32.000
P. bovis（n=10）	0.030-1.000	0.250-16.000	0.500-4.000	0.500-8.000	0.500-1.000	8.000	4.000	8.000	256.000	32.000
P. zopfii（n=5）	0.250-0.500	0.500-1.000	1.000-2.000	2.000-4.000	0.500-1.000	8.000	4.000	8.000	256.000	32.000
P. ciferrii（n=1）	0.015	0.250	0.500	0.500	0.500	8.000	4.000	8.000	256.000	32.000
P. miyajii（n=1）	0.120	16.000	8.00	1.000	0.250	8.000	4.000	8.000	256.000	32.000