Penicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in Japan
Penicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in Japan
复制标题
DOI：
10.1128/aac.00711-19
复制
发表时间：
2019-09-01
影响因子：
4.9
通讯作者：
Nagao, Miki
中科院分区：
文献类型：
--
作者：
Nakano, Satoshi;Fujisawa, Takao;Nagao, Miki
自引入肺炎球菌结合疫苗以来，日本非美罗培南敏感肺炎球菌的患病率一直在增加。在早期的研究中，我们证明日本的多重耐药血清型15A-ST63具有特定的pbp1a序列（pbp1a-13），可以促进美罗培南耐药。为了追踪 pbp1a 的起源，我们分析了血清型 19A-CC3111 的分离株，这是日本最流行的非美罗培南敏感克隆。我们使用全基因组测序分析了在日本回收的总共 119 株血清型 19A-CC3111 菌株。在119个分离株中，53个（44.5%）携带pbp1a-13，表明该克隆可能是pbp1a型的主要储存库，并且pbp1a区域可能在不同血清型菌株之间水平转移。单次获得 pbp1a-13 似乎仅引起青霉素耐药性，而不引起多重耐药性； pbp2b 和/或 pbp2x 区域中的青霉素结合蛋白 (PBP) 重组与 pbp1a-13 的获得相结合，导致多药耐药性。保守氨基酸基序分析表明，pbp1a 370SXXK、pbp2b 448SXN 和 pbp2x 337SXXN 基序是氨基酸取代的候选基序，可增加美罗培南、头孢噻肟和青霉素的 MIC。我们鉴定了一个与多药耐药性相关的特定克隆，尽管在使用核心基因组生成的系统发育树和仅使用 cps 基因座生成的系统发育树之间没有观察到相关性。所有测试的分离株均具有高度红霉素抗性，并且大多数在大环内酯外排基因组装（MEGA）元件中包含mefE，在Tn917中包含ermB，其插入Tn916中并表现出与Tn2017相同的结构。
Since the introduction of pneumococcal conjugate vaccines, the prevalence of non-meropenem-susceptible pneumococci has been increasing in Japan. In an earlier study, we demonstrated that multidrug-resistant serotype 15A-ST63 in Japan has a specific pbp1a sequence (pbp1a-13) that could promote meropenem resistance. To trace the origin of pbp1a, we analyzed isolates of serotype 19A-CC3111, which is the most prevalent non-meropenem-susceptible clone in Japan. We analyzed a total of 119 serotype 19A-CC3111 strains recovered in Japan using wholegenome sequencing. Of the 119 isolates, 53 (44.5%) harbored pbp1a-13, indicating that the clone may be the primary reservoir of the pbp1a type and that the pbp1a region may be horizontally transferred between different serotype strains. The single acquisition of pbp1a-13 seemed to cause only penicillin resistance and not multidrug resistance; a combination of penicillin-binding protein (PBP) recombination in the pbp2b and/or pbp2x region(s) with acquisition of pbp1a-13 caused multidrug resistance. Conserved amino acid motif analysis suggested that the pbp1a 370SXXK, pbp2b 448SXN, and pbp2x 337SXXN motifs were the candidates for amino acid substitutions increasing the MICs of meropenem, cefotaxime, and penicillin. We identified a specific clone that was correlated with multidrug resistance, although no correlation was observed between phylogenetic trees generated using core genomes and those generated with only the cps locus. All tested isolates were highly erythromycin resistant, and most harbored mefE within macrolide efflux genetic assembly (MEGA) elements and ermB within Tn917, which was inserted within Tn916 and exhibited a structure identical to that of Tn2017.