A Bowman–Birk Inhibitor from the Seeds of Luetzelburgia auriculata Inhibits Staphylococcus aureus Growth by Promoting Severe Cell Membrane Damage

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2018-07, Vol.81 (7), p.1497-1507
• Main Authors: Martins, Thiago F, Vasconcelos, Ilka M, Silva, Rodolpho G. G, Silva, Fredy D. A, Souza, Pedro F. N, Varela, Anna L. N, Albuquerque, Louise M, Oliveira, Jose T. A
• Format: Article
• Language: English
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.7b00545

Staphylococcus aureus is a multidrug-resistant bacterium responsible for several cases of hospital-acquired infections, which constitute a global public health problem. The introduction of new healthcare strategies and/or the discovery of molecules capable of inhibiting the growth or killing S. aureus would have a huge impact on the treatment of S. aureus-mediated diseases. Herein, a Bowman–Birk protease inhibitor (LzaBBI), with strong in vitro antibacterial activity against S. aureus, was purified to homogeneity from Luetzelburgia auriculata seeds. LzaBBI in its native form is a 14.3 kDa protein and has a pI of 4.54, and its NH2-terminal sequence has high identity with other Bowman–Birk inhibitors. LzaBBI showed a mixed-type inhibitory activity against both trypsin and chymotrypsin, respectively, and it remained stable after both boiling at 98 °C for 120 min and incubation at various pHs. Scanning electron microscopy revealed that LzaBBI disrupted the S. aureus membrane integrity, leading to bacterial death. This study suggests that LzaBBI is a powerful candidate for developing a new antimicrobial to overcome drug resistance toward reducing hospital-acquired infections caused by S. aureus.