Expanded profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39.
Expanded profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39.
复制标题
肺炎链球菌D39中青霉素结合蛋白的β-内酰胺选择性的扩展分析。
DOI：
10.1515/hsz-2021-0386
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发表时间：
2022-03-28
影响因子：
3.7
通讯作者：
Carlson, Erin E.
中科院分区：
文献类型：
--
作者：
Sharan, Deepti;Carlson, Erin E.
青霉素结合蛋白（PBP）是细菌细胞分裂不可或缺的，因为它们介导细胞壁成熟的最后步骤。选择性荧光探针可用于了解单个PBPs的作用，包括它们在细菌生长和分裂过程中的定位和活性。为了开发用于PBP成像的新的选择性探针，筛选了几种β-内酰胺抗生素，因为已知它们在体内共价结合PBP。在肺炎链球菌D39菌株IU 1945的未包封衍生物中评价了16种市售β-内酰胺抗生素的PBP抑制特性。这些β-内酰胺类药物以前未在S.这些数据增加了我们以前报道的从20种化合物的文库中获得的数据。我们研究了7种青霉素类、3种碳青霉烯类和6种头孢菌素类。发现这些β-内酰胺中的大多数对PBP 2x和PBP 3具有共选择性，如我们先前的研究所述。16种抗生素中有6种对PBP 3具有选择性，1种对PBP 1a和PBP 3具有共选择性。总体而言，这项工作扩大了可用于开发未来基于β-内酰胺的探针用于特异性肺炎球菌PBP标记的化学空间，并且这些方法可用于开发用于其他细菌物种中PBP标记的探针。
Penicillin-binding proteins (PBPs) are integral to bacterial cell division as they mediate the final steps of cell wall maturation. Selective fluorescent probes are useful for understanding the role of individual PBPs, including their localization and activity during growth and division of bacteria. For the development of new selective probes for PBP imaging, several β-lactam antibiotics were screened, as they are known to covalently bind PBP in vivo. The PBP inhibition profiles of 16 commercially available β-lactam antibiotics were evaluated in an unencapsulated derivative of the D39 strain of Streptococcus pneumoniae, IU1945. These β-lactams have not previously been characterized for their PBP inhibition profiles in S. pneumoniae and these data augment those obtained from a library of 20 compounds that we previously reported. We investigated seven penicillins, three carbapenems, and six cephalosporins. Most of these β-lactams were found to be co-selective for PBP2x and PBP3, as was noted in our previous studies. Six out of 16 antibiotics were selective for PBP3 and one molecule was co-selective for PBP1a and PBP3. Overall, this work expands the chemical space available for development of future β-lactam-based probes for specific pneumococcal PBP labeling and these methods can be used for the development of probes for PBP labelling in other bacterial species.
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影响因子：
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作者：
Sharifzadeh S;Dempwolff F;Kearns DB;Carlson EE
通讯作者：
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