Genetics of Chromosomally Mediated Intermediate Resistance to Ceftriaxone and Cefixime in Neisseria gonorrhoeae
Genetics of Chromosomally Mediated Intermediate Resistance to Ceftriaxone and Cefixime in Neisseria gonorrhoeae
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DOI：
10.1128/aac.00304-09
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发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Nicholas, Robert A.
中科院分区：
文献类型：
--
作者：
Zhao, Shuqing;Duncan, Margaret;Nicholas, Robert A.
所有对头孢曲松和头孢克辛敏感性降低的淋球菌(头孢菌素中间耐药株)都含有编码青霉素结合蛋白2(PBP 2)的嵌合体PenA等位基因，与野生型PBP 2序列相比有近60个氨基酸差异，以及一组高水平青霉素耐药所需的耐药决定基因(即mtrR、penB和/或ponA1)。为了确定这些决定因素对降低头孢曲松和头孢克肟敏感性的单独贡献，我们从头孢菌素(I)株35/02(PenA35)和一个或多个其他耐药决定因素中创建了含有马赛克Pena等位基因的同基因菌株，并测定了青霉素G、头孢曲松和头孢克肟的MIC。大多数头孢克肟耐药性是由penA35等位基因决定的，只有一小部分来自mtrR和penB，而头孢曲松耐药性几乎同样依赖于mtrR和penB。与高水平的青霉素耐药不同，ponA1等位基因似乎对Cave(I)并不重要。包含所有四个决定簇的菌株对头孢曲松和头孢克辛的耐药性增加，但不能达到供体头孢菌素(I)菌株的水平，这表明头孢菌素(I)菌株与高水平青霉素耐药菌株类似，含有额外的未知决定因素，达到供体抗药性水平所必需的。我们的数据还表明，最初的头孢菌素(I)菌株是由共生奈瑟氏菌的PenA基因转化为青霉素耐药菌株而产生的，该菌株已含有mtrR、penB、ponA1和参与高水平青霉素耐药的未知基因(S)。
All strains of Neisseria gonorrhoeae with reduced susceptibility to ceftriaxone and cefixime (cephalosporin-intermediate-resistant [Ceph(i)] strains) contain a mosaic penA allele encoding penicillin-binding protein 2 (PBP 2) with nearly 60 amino acid differences compared to the sequence of wild-type PBP 2, together with a set of resistance determinants (i.e., mtrR, penB, and/or ponA1) that are required for high-level penicillin resistance. To define the individual contributions of these determinants to reduced susceptibility to ceftriaxone and cefixime, we created isogenic strains containing the mosaic penA allele from the Ceph(i) strain 35/02 (penA35) together with one or more of the other resistance determinants and determined the MICs of penicillin G, ceftriaxone, and cefixime. The majority of cefixime resistance is conferred by the penA35 allele, with only a small contribution coming from mtrR and penB, whereas ceftriaxone resistance is nearly equally dependent upon mtrR and penB. Unlike high-level penicillin resistance, the ponA1 allele does not appear to be important for Ceph(i). A strain containing all four determinants has increased resistance to ceftriaxone and cefixime but not to the levels that the donor Ceph(i) strain does, suggesting that Ceph(i) strains, similar to high-level-penicillin-resistant strains, contain an additional unknown determinant that is required to reach donor levels of resistance. Our data also suggest that the original Ceph(i) strains arose from the transformation of penA genes from commensal Neisseria species into a penicillin-resistant strain already harboring mtrR, penB, ponA1, and the unknown gene(s) involved in high-level penicillin resistance.