Cefuroxime resistance in non-beta-lactamase Haemophilus influenzae is linked to mutations in ftsI.
Cefuroxime resistance in non-beta-lactamase Haemophilus influenzae is linked to mutations in ftsI.
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非 β-内酰胺酶流感嗜血杆菌的头孢呋辛耐药性与 ftsI 突变有关。
DOI：
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发表时间：
2003
影响因子：
5.2
通讯作者：
T. Walsh
中科院分区：
文献类型：
--
作者：
K. Straker;M. Wootton;A. Simm;P. Bennett;A. Macgowan;T. Walsh
对14株头孢呋肟耐药（CXM（R））的B型流感嗜血杆菌（Haemophilus influenzae type b）和3株低CXM MIC的临床分离株的青霉素结合蛋白（PBP）基因dacA、dacB和ftsI进行了分子鉴定。用5788菌株转化H.流感病毒Rd与CXM（R）的pbp序列进行比较，以直接比较相同遗传背景下的pbp。dacA和dacB基因产物中没有明显的突变可能与CXM（R）相关。特别是ftsI基因产物中的一个氨基酸取代，S357 N，可以产生CXM（R）。对CXM（R）转化体的序列分析也涉及FtsI;在这种情况下，取代是V511 A和R517 H。为了验证S357 N取代，将H.流感病毒FtsI通过S. pneumoniae PBP 2X结构，给出α-碳链的平均均方根偏差为0.5 A。S357 N取代改变了残基的大小和电荷。对S357 N对CXM（R）的贡献的一种解释是天冬酰胺侧链产生不利的空间位阻，其中瓦尔-362的侧链改变天冬酰胺残基的扭转角，这又可能影响邻近活性位点的环V362-P366的位置。虽然其他小组已经研究了H。流感PBP在氨苄青霉素耐药性中的作用，这是第一份分析其在CXM（R）中作用的报告。
The penicillin binding protein (PBP) genes dacA, dacB and ftsI from 14 cefuroxime-resistant (CXM(R)) isolates and three clinical isolates with low CXM MIC for non-beta-lactamase-producing Haemophilus influenzae type b were molecularly characterized. One strain, 5788, was used to transform H. influenzae Rd to CXM(R) for direct comparison of the pbps in the same genetic background. No obvious mutations in the dacA and dacB gene products could be associated with CXM(R). One amino acid substitution in the ftsI gene product in particular, S357N, could give rise to CXM(R). Sequence analysis from the CXM(R) transformants also implicated FtsI; in this case, the substitutions were V511A and R517H. To verify S357N substitution, the protein sequence of H. influenzae FtsI was threaded through the S. pneumoniae PBP 2X structure giving an average root mean square deviation of the alpha-carbon chains of 0.5 A. The S357N substitution alters both the residue size and charge. One explanation for the contribution of S357N to CXM(R) is that the asparagine side-chain produces unfavourable steric hindrance with the side chain of Val-362 changing the torsion angles of the asparagine residue, which in turn may influence the position of the loop V362-P366 adjacent to the active site. Whilst other groups have examined the contribution of H. influenzae PBPs in ampicillin resistance, this is the first report analysing their role in CXM(R).
流感嗜血杆菌的氨苄西林耐药性和青霉素结合蛋白。
DOI：
10.1099/00221287-132-10-2855
发表时间：
1986
期刊：
Journal of general microbiology
影响因子：
--
作者：
Serfass,DA;Mendelman,PM;Chaffin,DO;Needham,CA
通讯作者：
Needham,CA