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Sodium tetraphenylborate displays selective bactericidal activity against N. meningitidis and N. gonorrhoeae and is effective at reducing bacterial infection load

Bernet, Eve, Lebughe, Marthe, Vincent, Antony T., Haghdoost, Mohammad Mehdi, Golbaghi, Golara, Laplante, Steven ORCID: https://orcid.org/0000-0003-2835-5789, Castonguay, Annie ORCID: https://orcid.org/0000-0001-5705-6353 et Veyrier, Frédéric ORCID: https://orcid.org/0000-0002-8574-0547 (2021). Sodium tetraphenylborate displays selective bactericidal activity against N. meningitidis and N. gonorrhoeae and is effective at reducing bacterial infection load Antimicrobial Agents and Chemotherapy , vol. 65 , nº 2. p. 1-14. DOI: 10.1128/AAC.00254-20.

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Résumé

Neisseria meningitidis and Neisseria gonorrhoeae, two highly related species that may have emerged from a common commensal ancestor, constitute major human threats. Vaccines are available to prevent N. meningitidis infection, whereas for N. gonorrhoeae, there are only a limited number of antibiotics available. Unfortunately, some strains of these species are rapidly evolving and capable of escaping human interventions. Thus, it is now urgent to develop new avenues to fight these bacteria. This study reports that a boron-based salt, sodium tetraphenylborate (NaBPh(4)), displays high bactericidal activity and remarkable specificity against N. meningitidis and N. gonorrhoeae Other closely related commensal species such as N. lactamica, found in the normal flora of healthy individuals were found to be less affected even at 5-fold higher doses of NaBPh(4) This specificity was further observed where much lower sensitivity was found for the more distant Neisseriaceae (such as N. elongata or Kingella oralis) and completely unrelated species. A significant boron uptake by N. meningitidis cells was observed after incubation with 5 μM of NaBPh(4), as measured by ICP-MS, suggesting that this drug candidate's target(s) could be located intracellularly or within the cell envelope. Furthermore, mutants with a slightly decreased susceptibility displayed an alteration in genes coding for cell-envelope elements, which reduced their virulence in an animal model of infection. Finally, a single dose of NaBPh(4) resulted in a significant reduction in bacterial burden in a mouse model of N. meningitidis bacteremia. Although numerous boron-containing species were previously reported for their complex biological activities, the observation of this narrow selectivity is unprecedented and of potential importance from a therapeutic standpoint.

Type de document: Article
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 21 avr. 2021 22:49
Dernière modification: 16 févr. 2022 15:49
URI: https://espace.inrs.ca/id/eprint/11550

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