Multilocus Sequence Typing Reveals Clonality of Fluconazole-Nonsusceptible Candida tropicalis: A Study From Wuhan to the Global

Abstract

Candida tropicalis is a globally distributed human pathogenic yeast, and its increasing resistance to azoles makes clinical treatment difficult. In this study, we investigated the clinical features, azole resistance and genetic relatedness of 87 C. tropicalis isolates from central China and combined with the global database to explore the relationship between genetic information and fluconazole susceptibility. Of the 55 diploid sequence types (DSTs) identified by multilocus sequence typing (MLST), 27 DSTs were new to the C. tropicalis MLST database. Fluconazole-nonsusceptible (FNS) isolates were genetically closely related. goeBURST analysis showed that DST225, DST376, DST506, and DST546 formed a distinct and unique FNS clonal complex (CC) in Wuhan. The local FNS CC belongs to the large FNS CC (CC2) in China, in which the putative founder DST225 has been reported from the environment. The three most prevalent types (DST506, DST525, and DST546) in Wuhan had high minimum inhibitory concentrations (MICs) for antifungal azoles, and the six possible nosocomial transmissions we captured were all FNS strains, most of which were from CC2. Unique FNS CCs have been found in Singapore (CC8) and India (CC17) and are close to China’s CC2 in the minimum spanning tree. There were no FNS CCs outside Asia. This study is the first to reveal a significant correlation between genetic information and fluconazole susceptibility worldwide and to trace geographical locations, which is of great value for molecular epidemiological surveillance and azole-resistance study of C. tropicalis globally.

Mechanisms of Azole Resistance and Trailing in Candida tropicalis Bloodstream Isolates

“…Given isavuconazole shares more similar chemical structures with short-chained azoles, our and other reports [26] demonstrated good correlation between isavuconazole and fluconazole/voriconazole. This is of particular concern in view of the emerging pan-azole-resistant clone, CC3, in Asia [5,7,10,11]. As shown in this study, C. tropicalis isolates exhibiting cross-resistance between isavuconazole and other azoles were collected in 2017, while isavuconazole was introduced in Asia in 2019.…”

“…The proportion of C. tropicalis among Candida species causing candidaemia are relatively high in tropical Asia and Latin America compared to other continents [2,3]. Azole-resistant C. tropicalis clinical isolates have emerged worldwide [4][5][6][7][8][9][10][11]. This has become particularly problematic in the Asia-Pacific region since 2010 [4,5,7,10,11].…”

“…Azole-resistant C. tropicalis clinical isolates have emerged worldwide [4][5][6][7][8][9][10][11]. This has become particularly problematic in the Asia-Pacific region since 2010 [4,5,7,10,11]. Clonal complex 3 (CC3) with high-level azole resistance were isolated from patients and environments [5,7,10,11].…”

Risk Factors and Outcomes of Non-albicans Candida Bloodstream Infection in Patients with Candidemia at Siriraj Hospital—Thailand’s Largest National Tertiary Referral Hospital

“…Therefore, empirical antifungal treatment with echinocandins or amphotericin B product in candidemia patients with risk factors for C. tropicalis infection is strongly recommended. In our study, most of the patients infected with fluconazole-resistant C. tropicalis did not have a history of azole exposure and they may be acquired from the environment [ 21 ]. Azoles have been used in agriculture in Thailand and the link between fluconazole-resistant Candida and environmental azole exposure needs to be investigated.…”

The emerging threat antifungal-resistant Candida tropicalis in humans, animals, and environment

“…The burden of antifungal-resistant Candida tropicalis in humans, animals, and the environment Recent evidence points out that there is an increasing prevalence of fluconazole and multidrug resistance among C. tropicalis recovered from humans (Favarello et al, 2021;Wang et al, 2021). In China, some centers report a prevalence of 20-50% of fluconazole non-susceptibility among C. tropicalis clinical isolates (Fan et al, 2019;Wang et al, 2020;Wang et al, 2021), while in Algeria and Japan, reports show that more than 30% of C. tropicalis bloodstream isolates are fluconazole-resistant (Megri et al, 2020;Khalifa et al, 2022). In Turkey, a recent multicentric study showed that over 10% of the bloodstream isolates collected from 2017 to 2019 are resistant to fluconazole (Arastehfar et al, 2020b).…”