Controlling resistant bacteria with a novel class of β 2-lactamase inhibitor peptides

From rational design to in vivo analyses

Santi M. Mandal, Ludovico Migliolo, Osmar N. Silva, Isabel C M Fensterseifer, Celio Faria-Junior, Simoni C. Dias, Amit Basak, Tapas Hazra, Octávio L. Franco

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Peptide rational design was used here to guide the creation of two novel short β 2-lactamase inhibitors, here named dBLIP-1 and-2, with length of five amino acid residues. Molecular modeling associated with peptide synthesis improved bactericidal efficacy in addition to amoxicillin, ampicillin and cefotaxime. Docked structures were consistent with calorimetric analyses against bacterial β 2-lactamases. These two compounds were further tested in mice. Whereas commercial antibiotics alone failed to cure mice infected with Staphylococcus aureus and Escherichia coli expressing β 2-lactamases, infection was cleared when treated with antibiotics in combination with dBLIPs, clearly suggesting that peptides were able to neutralize bacterial resistance. Moreover, immunological assays were also performed showing that dBLIPs were unable to modify mammalian immune response in both models, reducing the risks of collateral effects. In summary, the unusual peptides here described provide leads to overcome β 2-lactamase-based resistance, a remarkable clinical challenge.

Original languageEnglish (US)
Article number6015
JournalScientific Reports
Volume4
DOIs
StatePublished - Aug 11 2014

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Bacteria
Peptides
Anti-Bacterial Agents
Cefotaxime
Amoxicillin
Ampicillin
Staphylococcus aureus
Escherichia coli
Amino Acids
Infection

ASJC Scopus subject areas

  • General

Cite this

Mandal, S. M., Migliolo, L., Silva, O. N., Fensterseifer, I. C. M., Faria-Junior, C., Dias, S. C., ... Franco, O. L. (2014). Controlling resistant bacteria with a novel class of β 2-lactamase inhibitor peptides: From rational design to in vivo analyses. Scientific Reports, 4, [6015]. https://doi.org/10.1038/srep06015

Controlling resistant bacteria with a novel class of β 2-lactamase inhibitor peptides : From rational design to in vivo analyses. / Mandal, Santi M.; Migliolo, Ludovico; Silva, Osmar N.; Fensterseifer, Isabel C M; Faria-Junior, Celio; Dias, Simoni C.; Basak, Amit; Hazra, Tapas; Franco, Octávio L.

In: Scientific Reports, Vol. 4, 6015, 11.08.2014.

Research output: Contribution to journalArticle

Mandal, SM, Migliolo, L, Silva, ON, Fensterseifer, ICM, Faria-Junior, C, Dias, SC, Basak, A, Hazra, T & Franco, OL 2014, 'Controlling resistant bacteria with a novel class of β 2-lactamase inhibitor peptides: From rational design to in vivo analyses', Scientific Reports, vol. 4, 6015. https://doi.org/10.1038/srep06015
Mandal, Santi M. ; Migliolo, Ludovico ; Silva, Osmar N. ; Fensterseifer, Isabel C M ; Faria-Junior, Celio ; Dias, Simoni C. ; Basak, Amit ; Hazra, Tapas ; Franco, Octávio L. / Controlling resistant bacteria with a novel class of β 2-lactamase inhibitor peptides : From rational design to in vivo analyses. In: Scientific Reports. 2014 ; Vol. 4.
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