Antibacterial action mechanisms and mode of trypsin inhibitors: a systematic review

Abstract

This systematic review (SR) aimed to gather studies describing the antibacterial action mechanisms and mode of trypsin inhibitors. The review protocol was registered (PROSPERO: CRD42020189069). Original articles resulting from studies in animal models, in bacterial culture, and using cells that describe antibacterial action of trypsin inhibitor-type peptides or proteins were selected in PubMed, Science Direct, Scopus, Web of Science, BVS, and EMBASE. The methodological quality assessment was performed using the PRISMA and OHAT tool. 2382 articles were retrieved, 17 of which were eligible. Four studies demonstrated the action mechanism directly on the bacterial membrane, and the fifth study on endogenous proteases extracted from the bacteria themselves. The antibacterial action mode was presented in the other studies, which can generate bacteriostatic or bactericidal effects without describing the mechanisms. This study generated information to enable new preclinical or clinical studies with molecules contributing to public health.

Keywords: Antimicrobial peptides; bacteria; bioactive proteins; infectious diseases.

Figure 1.

Flowchart for selecting articles per the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis (PRISMA) to answer the question: what are the antibacterial action mechanisms of trypsin inhibitor-type peptides or proteins?

Figure 2.

Antibacterial effects of trypsin inhibitors. Trypsin inhibitors can act by generating a bactericidal effect, causing the death of bacteria or a bacteriostatic effect, where bacterial growth is suppressed (keeping them in the stationary growth phase). pYR: peptide synthesised from anuran skin secretions; RV3: peptide synthesised from sunflower trypsin inhibitor; IVTI: Inga Vera seed trypsin inhibitor; AEBSF: 4-(2-aminoethyl) benzenesulfonyl serine protease inhibitor; K-SL: inhibitor synthesised from frog skin secretion; Adevonin: synthetic inhibitor produced from Adenanthera pavonin trypsin inhibitor; LzaBBI: synthetic inhibitor produced from the inhibitor of L. auriculata seeds; JcTI-I: inhibitor produced from Jatropha curcas seed; Adepamycin: synthetic inhibitor produced from Adenanthera pavonin trypsin inhibitor; SMTI: trypsin inhibitor isolated from Streptomyces misionensis; TIH3F: peptide synthesised from the junction of cathelicidin with a trypsin inhibitory loop; PtPLC: inhibitor synthesised from the arthropod serine protease inhibitor, Portunus trituberculatus; ORB1: trypsin inhibitor produced from amphibian skin; AnTI: Acacia nilotic L trypsin inhibitor; RfIP1: Rhamnus frangula trypsin inhibitor; API: trypsin inhibitor from Albizia amara seeds; S-NO-hAAT: inhibitor synthesised from human α1-antitrypsin