金黃色葡萄球菌之抗紅黴素基因結構分析

金黃色葡萄球菌為臨床上常見的病原菌，其抗藥一直是嚴重的問題。紅黴素為臨床上治療methicillin susceptible Staphylococcus aureus (MSSA)的藥物，過去研究發現在台灣21間醫院抗紅黴素MSSA 比例(161株)佔35%，所以仍有一定的重要性。此外，MSSA可藉由mobile genetic elements (MGE) 傳遞 erm 基因給methicillin resistant S. aureus (MRSA)。因此本研究探討MRSA及MSSA抗紅黴素基因之流行病學分布及其基因結構。菌株為來自台大醫院2013至2015年臨床檢體分離具紅黴素抗性之金黃色葡萄球菌MSSA及MRSA，血液培養分離菌株包括MRSA 286株及MSSA 59株。紅黴素抗藥基因分析顯示286株來自血液MRSA以攜帶ermA基因為最大宗共有111株(39%)，而 MSSA 以攜帶msrA/B基因最多，在59株中共測得25株。較特別的是2015年MSSA血液檢體發現有一株帶有ermT基因，ermT基因在其他研究曾指出跟 livestock-associated MRSA (LA-MRSA)及LA-MSSA有關，換句話說，此基因可能在動物與人之間傳遞。分析其spa type及MLST之sequence type，結果顯示此菌株屬於t1379及ST834。其中ST834屬於 (clonal complex) CC9，在過去文獻提到CC9跟亞洲家畜相關金黃葡萄球菌有關，而本篇為第一個發現MSSA ST834-CC9菌株攜帶ermT基因。以PCR mapping與southern blot確認此ermT附近基因結構與已知攜帶ermT基因的MSSA NTUH-8300結構不同。此外，也分析CoNS (NTUH-4483, NTUH-2381-1) 與S. aureus (NTUH-154, pUR3912) 攜帶ermT基因結構，在此篇研究發現不同物種其ermT基因周圍結構有些不一樣。為了更探討台大醫院其他檢體中是否有攜帶ermT的菌株，擴大檢體收集範圍並篩選自2016年4月到6月具紅黴素抗性的非血液檢體，結果並無發現攜帶ermT基因，原因推測為收集時間太短的關係。

關鍵字

MSSA ； MRSA ； ermT ； LA-MSSA ； CC9 ； ST834 ； CoNS

並列摘要

Staphylococcus aureus is a major human pathogen that causes a board range of clinical infections. The use of various antibiotics over the years has led to evolution of multidrug-resistant strains. Erythromycin have important therapeutic roles in methicillin susceptible Staphylococcus aureus (MSSA). Erythromycin-resistant MSSA was collected in 2000 from 21 hospitals in Taiwan. Of the 161 MSSA isolates, 56 (35%) were resistant to erythromycin. As far as we know, erm gene can be transferred to methicillin resistant S. aureus (MRSA) by mobile genetic elements, which is usually carried by MSSA. Thus, the present study demonstrated information on the prevalence of erythromycin-resistance and molecular epidemiology of MSSA and MRSA in National Taiwan University Hosipital. A total of 345 blood isolates of erythromycin-resistant MRSA (286) and MSSA (59) strains were obtained from 2013 to 2015. The prevalence of ermA gene was 39% among MRSA and msrA/B gene was detected in MSSA predominantly. In this study, we found a strain, NTUH-154, which was an MSSA isolate of blood culture that carried ermT gene. The ermT gene has been detected in LA-MRSA and LA-MSSA many times. Besides, ermT gene has also been concerned with cross-species transmission, that is, animal to human. NTUH-154 was subjected to spa typing and multilocus sequence type and the results showed that NTUH-154 belonged to t1379 and ST834 which was classified as CC9. CC9 has been referred to as the most pandemic LA-MRSA and LA-MSSA in most Asian countries. This is the first report of the ermT gene in a ST834-CC9 MSSA. The structure of chromosomal ermT gene in ST834-CC9 NTUH-154 was demonstracted by PCR mapping followed by sequencing and was different from the previous isolate of ST398-CC398 NTUH-8300. On the other hand, we also analyzed the isolates from CoNS that carried the ermT gene. This study also compared the genetic environment of ermT gene between S. aureus (NTUH-154, pUR3912) and CoNS (NTUH-4483, NTUH-2381-1). We found out that different species harbore different combination of genetic environment of ermT gene. Erythromycin-resistant S. aureus non-blood culture isolates were collected during Apr-Jun in 2016. None of these isolates carried ermT gene and this may be due to short period of specimen collection.

並列關鍵字

MSSA ； MRSA ； ermT ； LA-MSSA ； CC9 ； ST834 ； CoNS

參考文獻

71. 萬采玟，甲氧西林敏感金黃色葡萄球菌之抗紅黴素基因結構分析. 國立台灣大學，2014年

72. 鄭耀瑜，凝固酶陰性葡萄球菌之抗紅黴素基因分析. 國立台灣大學，2016年

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金黃色葡萄球菌之抗紅黴素基因結構分析

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