Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes
Candida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. gl...
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01523/full |
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| author | Seung A. Byun Eun Jeong Won Mi-Na Kim Wee Gyo Lee Kyungwon Lee Hye Soo Lee Young Uh Kelley R. Healey David S. Perlin Min Ji Choi Soo Hyun Kim Jong Hee Shin |
| author_facet | Seung A. Byun Eun Jeong Won Mi-Na Kim Wee Gyo Lee Kyungwon Lee Hye Soo Lee Young Uh Kelley R. Healey David S. Perlin Min Ji Choi Soo Hyun Kim Jong Hee Shin |
| author_sort | Seung A. Byun |
| collection | DOAJ |
| description | Candida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. glabrata. To address this question in Korea, we investigated antifungal resistance and non-synonymous mutations of the mismatch repair gene (msh2 mutations) in C. glabrata BSI isolates, as well as associated clinical characteristics, and compared the results according to MLST genotype. We assessed a total of 209 C. glabrata BSI isolates from seven hospitals in Korea for 2 years (2009 and 2014). Clinical features of candidemia and their outcomes were analyzed for 185 available cases. According to MLST, ST7 (47.8%) was the most common type, followed by ST3 (22.5%); the remainder represented 28 types of minor STs (29.7%). Fluconazole-resistance (FR) rates for ST7, ST3, and other strains were 9.0% (9/100), 8.5% (4/47), and 4.8% (3/62), respectively, and all were susceptible to amphotericin B and micafungin. All ST7 isolates harbored the V239L mutation in msh2, known to confer hypermutability, while 91.5% of ST3 isolates did not harbor the msh2 mutation. Overall, isolates of the same ST had identical msh2 mutations, with the exception of nine isolates. The msh2 mutations were identified in 68.8% (11/16) of the FR isolates and 67.4% (130/193) of the fluconazole susceptible-dose dependent isolates. There was no significant difference in all clinical characteristics between ST3 and ST7. However, the 30-day mortality of C. glabrata candidemia due to the two major ST (ST3 or ST7) strains was significantly higher than that of candidemia due to other minor ST strains (45.1 vs. 25.0%, p < 0.05). Multivariate logistic regression analysis also showed that two major STs (ST3 and ST7) were independent predictors of 30-day mortality. This study showed for the first time that two STs (ST7 and ST3) were predominant among BSI isolates in Korea, and that C. glabrata BSI isolates belonging to two major MLST genotypes are characterized by higher mortality. In addition, most msh2 mutations align with MLST genotype, irrespective of FR. |
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| spelling | doaj.art-4f68e8994b5b43708395ef582adefff12022-12-22T00:55:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-07-01910.3389/fmicb.2018.01523354007Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical OutcomesSeung A. Byun0Eun Jeong Won1Mi-Na Kim2Wee Gyo Lee3Kyungwon Lee4Hye Soo Lee5Young Uh6Kelley R. Healey7David S. Perlin8Min Ji Choi9Soo Hyun Kim10Jong Hee Shin11Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South KoreaDepartment of Laboratory Medicine, Ajou University School of Medicine, Suwon, South KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Laboratory Medicine, Chonbuk National University Hospital, Jeonju, South KoreaDepartment of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, South KoreaPublic Health Research Institute, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, NY, United StatesPublic Health Research Institute, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, NY, United StatesDepartment of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South KoreaDepartment of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South KoreaCandida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. glabrata. To address this question in Korea, we investigated antifungal resistance and non-synonymous mutations of the mismatch repair gene (msh2 mutations) in C. glabrata BSI isolates, as well as associated clinical characteristics, and compared the results according to MLST genotype. We assessed a total of 209 C. glabrata BSI isolates from seven hospitals in Korea for 2 years (2009 and 2014). Clinical features of candidemia and their outcomes were analyzed for 185 available cases. According to MLST, ST7 (47.8%) was the most common type, followed by ST3 (22.5%); the remainder represented 28 types of minor STs (29.7%). Fluconazole-resistance (FR) rates for ST7, ST3, and other strains were 9.0% (9/100), 8.5% (4/47), and 4.8% (3/62), respectively, and all were susceptible to amphotericin B and micafungin. All ST7 isolates harbored the V239L mutation in msh2, known to confer hypermutability, while 91.5% of ST3 isolates did not harbor the msh2 mutation. Overall, isolates of the same ST had identical msh2 mutations, with the exception of nine isolates. The msh2 mutations were identified in 68.8% (11/16) of the FR isolates and 67.4% (130/193) of the fluconazole susceptible-dose dependent isolates. There was no significant difference in all clinical characteristics between ST3 and ST7. However, the 30-day mortality of C. glabrata candidemia due to the two major ST (ST3 or ST7) strains was significantly higher than that of candidemia due to other minor ST strains (45.1 vs. 25.0%, p < 0.05). Multivariate logistic regression analysis also showed that two major STs (ST3 and ST7) were independent predictors of 30-day mortality. This study showed for the first time that two STs (ST7 and ST3) were predominant among BSI isolates in Korea, and that C. glabrata BSI isolates belonging to two major MLST genotypes are characterized by higher mortality. In addition, most msh2 mutations align with MLST genotype, irrespective of FR.https://www.frontiersin.org/article/10.3389/fmicb.2018.01523/fullCandida glabrataMLSTMSH2antifungal resistancecandidemiamortality |
| spellingShingle | Seung A. Byun Eun Jeong Won Mi-Na Kim Wee Gyo Lee Kyungwon Lee Hye Soo Lee Young Uh Kelley R. Healey David S. Perlin Min Ji Choi Soo Hyun Kim Jong Hee Shin Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes Frontiers in Microbiology Candida glabrata MLST MSH2 antifungal resistance candidemia mortality |
| title | Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes |
| title_full | Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes |
| title_fullStr | Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes |
| title_full_unstemmed | Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes |
| title_short | Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes |
| title_sort | multilocus sequence typing mlst genotypes of candida glabrata bloodstream isolates in korea association with antifungal resistance mutations in mismatch repair gene msh2 and clinical outcomes |
| topic | Candida glabrata MLST MSH2 antifungal resistance candidemia mortality |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01523/full |
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