Structural basis for antibiotic resistance by chloramphenicol acetyltransferase type A in <i>Staphylococcus aureus</i>

doi:10.1038/s41598-025-18365-4

	Structural basis for antibiotic resistance by chloramphenicol acetyltransferase type A in Staphylococcus aureus
	Wang, Kaiyue 1,2; Chen, Junwei 1,2; Li, Wanfang 3; Wang, Min 4; Fan, Tingwen 5; Bu, Dongbo 6,7; Ye, Sheng 1,2,8
	2025-10-23
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	15 期号:1 页码:13
摘要	Methicillin-resistant Staphylococcus aureus (MRSA) exemplifies high-level antibiotic resistance in this major human pathogen. Its resistance to chloramphenicol is majorly conferred by enzymatic inactivation via chloramphenicol acetyltransferases (CATs). This modification sterically blocks the antibiotic's ribosomal binding and thus neutralizes its inhibitory potency. Although CATs have been structurally studied across diverse bacteria species, the structures of S. aureus CATs (saCATs) have remained uncharacterized. To address this gap and elucidate species-specific resistance mechanisms, we determined the first high-resolution crystal structure of saCAT1, the prototypical saCAT enzyme. Structural analysis delineates the active site architecture and reveals the molecular basis for substrate recognition of both chloramphenicol and fusidic acid (FA). Further enzymatic assays demonstrated that the Km value against chloramphenicol is 16.9 mu M, and the Ki value of the inhibitor FA is 83.7 mu M, indicating that the inhibitory capacity of FA is relatively limited. These findings provide an essential structural framework for understanding chloramphenicol resistance in S. aureus and facilitate the rational design of novel antimicrobial strategies to combat multidrug-resistant pathogens.
关键词	Staphylococcus aureus Antibiotic resistance Chloramphenicol acetyltransferase Chloramphenicol Fusidic acid
DOI	10.1038/s41598-025-18365-4
收录类别	SCI
语种	英语
资助项目	Beijing Municipal Science & Technology Commission grant ; Beijing Regional Center of Large Research Instruments for Life Sciences
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001600537100011
出版者	NATURE PORTFOLIO
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/41591
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Bu, Dongbo; Ye, Sheng
作者单位	1.Beihang Univ, Sch Biomed Sci & Med Engn, Beijing 100191, Peoples R China 2.Beihang Univ, Key Lab Big Data Based Precis Med, Minist Ind & Informat Technol, Beijing 100862, Peoples R China 3.Rutgers State Univ, Sch Arts & Sci, New Brunswick, NJ 08901 USA 4.Chinese Acad Sci, Inst Biophys, State Key Lab Biomacromol, Beijing 100101, Peoples R China 5.Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Divers & Innovat Utilizat, Beijing 100101, Peoples R China 6.Chinese Acad Sci, SKLP, Inst Comp Technol, Beijing 100190, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100080, Peoples R China 8.Beihang Univ, Sch Engn Med, Beijing 100191, Peoples R China
推荐引用方式 GB/T 7714	Wang, Kaiyue,Chen, Junwei,Li, Wanfang,et al. Structural basis for antibiotic resistance by chloramphenicol acetyltransferase type A in Staphylococcus aureus[J]. SCIENTIFIC REPORTS,2025,15(1):13.
APA	Wang, Kaiyue.,Chen, Junwei.,Li, Wanfang.,Wang, Min.,Fan, Tingwen.,...&Ye, Sheng.(2025).Structural basis for antibiotic resistance by chloramphenicol acetyltransferase type A in Staphylococcus aureus.SCIENTIFIC REPORTS,15(1),13.
MLA	Wang, Kaiyue,et al."Structural basis for antibiotic resistance by chloramphenicol acetyltransferase type A in Staphylococcus aureus".SCIENTIFIC REPORTS 15.1(2025):13.