Spratt B G, Zhang Q Y, Jones D M, Hutchison A, Brannigan J A, Dowson C G
Microbial Genetics Group, School of Biological Sciences, University of Sussex, Brighton, United Kingdom.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):8988-92. doi: 10.1073/pnas.86.22.8988.
Non-beta-lactamase-producing, penicillin-resistant strains of Neisseria meningitidis produce altered forms of penicillin-binding protein 2 that have decreased affinity for penicillin. The sequence of the penicillin-binding protein 2 gene (penA) from a penicillin-resistant strain of N. meningitidis was compared to the sequence of the same gene from penicillin-sensitive strains and from penicillin-sensitive and penicillin-resistant strains of Neisseria gonorrhoeae. The penA genes from penicillin-sensitive strains of N. gonorrhoeae and N. meningitidis were 98% identical. The gene from the penicillin-resistant strain of N. meningitidis consisted of regions that were almost identical to the corresponding regions in the penicillin-sensitive strains (less than 0.2% divergence) and two regions that were very different from them (approximately 22% divergence). The two blocks of altered sequence have arisen by the replacement of meningococcal sequences with the corresponding regions from the penA gene of Neisseria flavescens and result in an altered form of penicillin-binding protein 2 that contains 44 amino acid substitutions and 1 amino acid insertion compared to penicillin-binding protein 2 of penicillin-sensitive strains of N. meningitidis. A similar introduction of part of the penA gene of N. flavescens, or a very similar commensal Neisseria species, appears to have occurred independently during the development of altered penA genes in non-beta-lactamase-producing penicillin-resistant strains of N. gonorrhoeae.
不产生β-内酰胺酶的耐青霉素脑膜炎奈瑟菌菌株产生了青霉素结合蛋白2的改变形式，其对青霉素的亲和力降低。将一株耐青霉素脑膜炎奈瑟菌的青霉素结合蛋白2基因（penA）序列与青霉素敏感菌株以及淋病奈瑟菌的青霉素敏感和耐青霉素菌株的相同基因序列进行了比较。淋病奈瑟菌和脑膜炎奈瑟菌青霉素敏感菌株的penA基因有98%的同一性。脑膜炎奈瑟菌耐青霉素菌株的基因由与青霉素敏感菌株相应区域几乎相同的区域（差异小于0.2%）和两个与其非常不同的区域（约22%的差异）组成。这两个改变的序列区域是通过用微黄奈瑟菌penA基因的相应区域替换脑膜炎奈瑟菌序列而产生的，与脑膜炎奈瑟菌青霉素敏感菌株的青霉素结合蛋白2相比，导致了一种改变形式的青霉素结合蛋白2，其含有44个氨基酸替换和1个氨基酸插入。在不产生β-内酰胺酶的耐青霉素淋病奈瑟菌菌株penA基因改变的过程中，似乎独立发生了类似的微黄奈瑟菌或非常相似的共生奈瑟菌属部分penA基因的引入。
