Kimura Kouji, Suzuki Satowa, Wachino Jun-ichi, Kurokawa Hiroshi, Yamane Kunikazu, Shibata Naohiro, Nagano Noriyuki, Kato Haru, Shibayama Keigo, Arakawa Yoshichika
Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan.
Antimicrob Agents Chemother. 2008 Aug;52(8):2890-7. doi: 10.1128/AAC.00185-08. Epub 2008 May 19.
Group B streptococci (GBS; Streptococcus agalactiae) are the leading cause of neonatal invasive diseases and are also important pathogens for adults. Penicillins are the drugs of first choice for the treatment of GBS infections, since GBS have been regarded to be uniformly susceptible to penicillins so far. Here we characterize the first strains of GBS with reduced penicillin susceptibility (PRGBS) identified in Japan. Fourteen PRGBS strains were clinically isolated from the sputa of elderly patients from 1995 to 2005; and the MICs of penicillin, oxacillin, and ceftizoxime ranged from 0.25 to 1 microg/ml, 2 to 8 microg/ml, and 4 to 128 microg/ml, respectively. Moreover, some strains were also insusceptible to ampicillin, cefazolin, cefepime, and cefotaxime. All the PRGBS isolates tested possessed a few amino acid substitutions adjacent to the conserved SSN and KSG motifs (amino acids 402 to 404 and 552 to 554, respectively) of PBP 2X, and the amino acid substitutions could be classified into two types, Q557E and V405A. Western blotting analysis of the 14 clinical isolates with anti-PBP 2X-specific serum suggested that the amount of PBP 2X among the 14 PRGBS isolates was reduced, although the 2 ATCC strains produced a significant amount of PBP 2X. The introduction of PRGBS-derived PBP 2X genes into penicillin-susceptible strains through allelic exchange elevated their penicillin insusceptibility, suggesting that these altered PBP 2X genes are responsible for the penicillin insusceptibility in PRGBS strains. In this study, we characterized for the first time PRGBS strains on a molecular basis, although several reports have so far mentioned the existence of beta-lactam-insusceptible GBS from a phenotypic standpoint.
B族链球菌（GBS；无乳链球菌）是新生儿侵袭性疾病的主要病因，也是成人的重要病原体。青霉素是治疗GBS感染的首选药物，因为迄今为止GBS一直被认为对青霉素普遍敏感。在此，我们对日本鉴定出的首批青霉素敏感性降低的GBS菌株（PRGBS）进行了特征描述。1995年至2005年期间，从老年患者痰液中临床分离出14株PRGBS菌株；青霉素、苯唑西林和头孢唑肟的最低抑菌浓度（MIC）分别为0.25至1微克/毫升、2至8微克/毫升和4至128微克/毫升。此外，一些菌株对氨苄西林、头孢唑林、头孢吡肟和头孢噻肟也不敏感。所有测试的PRGBS分离株在PBP 2X保守的SSN和KSG基序（分别为氨基酸402至404和552至554）附近都有一些氨基酸替换，这些氨基酸替换可分为两种类型，即Q557E和V405A。用抗PBP 2X特异性血清对14株临床分离株进行的蛋白质印迹分析表明，14株PRGBS分离株中PBP 2X的量减少，尽管2株美国典型培养物保藏中心（ATCC）菌株产生了大量PBP 2X。通过等位基因交换将PRGBS来源的PBP 2X基因导入青霉素敏感菌株中，提高了它们对青霉素的不敏感性，这表明这些改变的PBP 2X基因是PRGBS菌株中青霉素不敏感性的原因。在本研究中，我们首次在分子水平上对PRGBS菌株进行了特征描述，尽管迄今为止已有几份报告从表型角度提到了β-内酰胺不敏感GBS的存在。
