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Variations in the penA gene of Neisseria meningitidis increases penicillin resistance
By Sharon Guynup

In many countries, penicillin is no longer the invincible treatment for infections like meningitis and septicaemia. Now, European researchers have linked the declining efficacy of the antibiotic to mutations in the penA gene in Neisseria meningitidis, the bacterium behind these meningococcal infections.

N. meningitidis infects only humans, causing extremely invasive infections that require urgent medical care. The treatment of choice has been penicillin. But reports of reduced susceptibility to penicillin are on the rise—and the cause has been linked to structural changes in the penicillin-binding protein (PBP2), which is encoded by the penA gene.

Aude Antignac and colleagues at Institut Pasteur in Paris, France, collaborated with researchers from Greece and the Czech Republic to study the relationship between polymorphisms in the bacterium's penA gene and the resistance to penicillin. Their results are published in The Journal of Antimicrobial Chemotherapy.

The team analyzed strains of N. meningitidis from various genetic lineages that have been isolated in several countries over the last decade. They found strains with reduced susceptibility to penicillin (penl) that show a high degree of polymorphism, which frequently alters the amino acid sequence of PBP2.

But PBP2 was the only one of the bacterium's penicillin-binding proteins that contained variations. This finding suggests that penl strains are still evolving. If more of the bacterium's penicillin-binding proteins acquire mutations, full-blown resistance could come in the near future, much as it has with Streptococcus pneumoniae and other infectious bacteria.

Since reduced response to penicillin in N. meningitidis is directly linked to mutations of the penA gene, molecular methods of surveillance for these mutations may prove an invaluable tool for targeting penicillin-resistant strains. This will allow doctors to implement swift and effective treatment for dangerous meningococcal infections.

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Antignac, A. et al. Polymorphism of Neisseria meningitidis penA gene associated with reduced susceptibility to penicillin. J Antimicrob Chemother 47, 285-296 (March 2001).

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