Rimbara Emiko, Noguchi Norihisa, Kawai Takashi, Sasatsu Masanori
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392, Japan.
J Antimicrob Chemother. 2008 May;61(5):995-8. doi: 10.1093/jac/dkn051. Epub 2008 Feb 14.
To elucidate the relationship between the mutations of penicillin-binding protein (PBP)1, PBP2 and PBP3 and amoxicillin resistance in Helicobacter pylori.
The mutations detected only in clinical amoxicillin-resistant strains were determined by comparison of the deduced amino acid sequences of PBP1(HP0597), PBP2(HP1556) and PBP3(HP1565) encoded by the pbp1, ftsI and pbp2 genes, respectively, in 13 clinical H. pylori strains and three ATCC strains. The contribution of the mutations in PBPs was analysed by the natural transformation of the amoxicillin-susceptible strain ATCC 700392 with various combinations of the pbp1, ftsI and pbp2 genes from the amoxicillin-resistant strain TH743 (MIC of amoxicillin: 8 mg/L).
We initially identified six, four and two mutations of PBP1, PBP2 and PBP3, respectively, which were detected only in amoxicillin-resistant strains. By the natural transformation of an amoxicillin-susceptible strain ATCC 700392, we found that mutations in PBP1 and PBP3 conferred higher resistance to amoxicillin than mutations in PBP1 and PBP2, or mutations only in PBP1. Furthermore, mutations in PBP1, PBP2 and PBP3 conferred a 256-fold higher amoxicillin resistance when compared with ATCC 700392.
Multiple mutations in PBP2 and PBP3, in addition to mutations in PBP1, confer higher amoxicillin resistance in H. pylori.
阐明幽门螺杆菌中青霉素结合蛋白（PBP）1、PBP2和PBP3的突变与阿莫西林耐药性之间的关系。
通过比较分别由pbp1、ftsI和pbp2基因编码的PBP1（HP0597）、PBP2（HP1556）和PBP3（HP1565）的推导氨基酸序列，确定在13株临床幽门螺杆菌菌株和3株ATCC菌株中仅在临床阿莫西林耐药菌株中检测到的突变。通过用来自阿莫西林耐药菌株TH743（阿莫西林MIC：8mg/L）的pbp1、ftsI和pbp2基因的各种组合对阿莫西林敏感菌株ATCC 700392进行自然转化，分析PBPs中突变的作用。
我们最初分别鉴定出PBP1、PBP2和PBP3的6个、4个和2个突变，这些突变仅在阿莫西林耐药菌株中检测到。通过对阿莫西林敏感菌株ATCC 700392进行自然转化，我们发现PBP1和PBP3中的突变比PBP1和PBP2中的突变或仅PBP1中的突变赋予更高的阿莫西林耐药性。此外，与ATCC 700392相比，PBP1、PBP2和PBP3中的突变赋予的阿莫西林耐药性高256倍。
除PBP1中的突变外，PBP2和PBP3中的多个突变使幽门螺杆菌对阿莫西林具有更高的耐药性。
