| Title | Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. | | Author(s) | Zhao S, Duncan M, Tomberg J, Davies C, Unemo M, Nicholas RA | | Institution | Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina; and National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Orebro University Hospital, Orebro, Sweden. | | Source | Antimicrob Agents Chemother 2009 Jun 15. | | Abstract | Strains of Neisseria gonorrhoeae with reduced susceptibility to ceftriaxone and cefixime (ceph(I) strains) all contain a mosaic penA allele encoding penicillin-binding protein 2 (PBP 2) with nearly 60 amino acid differences compared to 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 from mtrR and penB, whereas ceftriaxone resistance is nearly equally dependent upon both. Unlike high-level penicillin resistance, the ponA1 allele does not appear to be important for ceph(I) resistance. A strain containing all four determinants has increased resistance to ceftriaxone and cefixime, but not to the levels of the donor ceph(I) strain, 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 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19528266 |
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