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Antimicrobial Agents and Chemotherapy, October 2006, p. 3317-3324, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00353-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Total Variation in the penA Gene of Neisseria meningitidis: Correlation between Susceptibility to ß-Lactam Antibiotics and penA Gene Heterogeneity

Sara Thulin,* Per Olcén, Hans Fredlund, and Magnus Unemo

National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden

Received 23 March 2006/ Returned for modification 22 May 2006/ Accepted 20 July 2006

In recent decades, the prevalence of Neisseria meningitidis isolates with reduced susceptibility to penicillins has increased. The intermediate resistance to penicillin (Peni) for most strains is due mainly to mosaic structures in the penA gene, encoding penicillin-binding protein 2. In this study, susceptibility to ß-lactam antibiotics was determined for 60 Swedish clinical N. meningitidis isolates and 19 reference strains. The penA gene was sequenced and compared to 237 penA sequences from GenBank in order to explore the total identified variation of penA. The divergent mosaic alleles differed by 3% to 24% compared to those of the designated wild-type penA gene. By studying the final 1,143 to 1,149 bp of penA in a sequence alignment, 130 sequence variants were identified. In a 402-bp alignment of the most variable regions, 84 variants were recognized. Good correlation between elevated MICs and the presence of penA mosaic structures was found especially for penicillin G and ampicillin. The Peni isolates comprised an MIC of >0.094 µg/ml for penicillin G and an MIC of >0.064 µg/ml for ampicillin. Ampicillin was the best antibiotic for precise categorization as Pens or Peni. In comparison with the wild-type penA sequence, two specific Peni sites were altered in all except two mosaic penA sequences, which were published in GenBank and no MICs of the corresponding isolates were described. In conclusion, monitoring the relationship between penA sequences and MICs to penicillins is crucial for developing fast and objective methods for susceptibility determination. By studying the penA gene, genotypical determination of susceptibility in culture-negative cases can also be accomplished.

* Corresponding author. Mailing address: Department of Clinical Microbiology, Örebro University Hospital, SE-701 85 Örebro, Sweden. Phone: 46 19 602 15 20. Fax: 46 19 12 74 16. E-mail: sara.thulin{at}orebroll.se.

Antimicrobial Agents and Chemotherapy, October 2006, p. 3317-3324, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00353-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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