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Antimicrobial Agents and Chemotherapy, November 1998, p. 2799-2803, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Gonococcal Resistance to beta -Lactams and Tetracycline Involves Mutation in Loop 3 of the Porin Encoded at the penB Locus

M. J. Gill,1,* S. Simjee,1 K. Al-Hattawi,2 B. D. Robertson,2 C. S. F. Easmon,2 and C. A. Ison2

Department of Infection, University of Birmingham Medical School, Birmingham,1 and Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, St. Mary's Campus, London,2 United Kingdom

Received 13 April 1998/Returned for modification 8 July 1998/Accepted 8 August 1998

penB is a chromosomal mutation that confers resistance to beta -lactams and tetracyclines and reduced susceptibility to quinolones in Neisseria gonorrhoeae. It is linked to the porin gene (por) and requires the increased expression of an efflux pump due to mtr. Transformation of a susceptible gonococcus (strain H1) with chromosomal DNA from strain FA140 (penA mtr penB; porin serovar IB1) and conjugal transfer of a beta -lactamase-expressing plasmid was used to produce isogenic strains for determination of equilibrium periplasmic penicillin concentrations by the method of Zimmermann and Rosselet (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368-372, 1977). In transformants with the Mtr and PenB phenotypes, equilibrium concentrations of penicillin were reduced. DNA sequence analysis of por from isogenic penB and penB+ transformants revealed 14 sequence differences; nine of these differences resulted in amino acid changes. Three amino acid changes were found in the putative gonococcal equivalent of the pore-constricting loop 3 of Escherichia coli OmpF. Two of these changes (Gly-101-Ala-102right-arrowAsp-Asp) result in an increased negative charge at this position in por loop 3. PCR products comprising the complete por gene from strain FA140 were transformed into strain H1-2 (penA mtr; porin serovar IB-3), with the resulting transformants having the antibiotic susceptibility phenotype associated with penB. penB-like mutations were found in loop 3 of clinical isolates of gonococci with chromosomally mediated resistance to penicillin. We conclude that penB is a mutation in loop 3 of por that reduces porin permeability to hydrophilic antibiotics and plays an important role in the development of chromosomally mediated resistance to penicillin and tetracycline in gonococci.

* Corresponding author. Mailing address: Department of Infection, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT., United Kingdom. Phone: 44 121 414 3436. Fax: 44 121 414 3454. E-mail: m.j.gill{at}bham.ac.uk.

Antimicrobial Agents and Chemotherapy, November 1998, p. 2799-2803, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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