Bacitracin is a non-competitive inhibitor of porcine M1 family neutral and glutamyl aminopeptidases

Arrebola, Yarini; Rivera, Laura Sanchez; Pedroso, Alejandro; McGuire, Rory; Tresanco, Mario Ernesto Valdés; Bergado, Gretchen; Charlí, Jean-Louis; Sánchez, Belinda; Alonso, Isel Pascual

doi:10.1080/14786419.2019.1678611

Cited by 8 publications

(2 citation statements)

References 15 publications

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“…Bacitracin is able to inhibit the activity of subtilisin-like serine endopeptidases, porcine glutamyl and neutral aminopeptidases [ 138 ], and protein disulfide isomerase [ 139 ]. Bacitracin inhibits the activity of a highly glycosylated cell surface membrane serine aminopeptidase (porcine dipeptidyl peptidase-IV), which plays a role in tumor progression and glucose metabolism [ 140 ].…”

Section: Antibacterial Substances Secreted By Bacillus Lich...mentioning

confidence: 99%

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications

Shleeva,

Kondratieva,

Kaprelyants

2023

Pharmaceutics

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Bacillus licheniformis produces several classes of antimicrobial substances, including bacteriocins, which are peptides or proteins with different structural composition and molecular mass: ribosomally synthesized by bacteria (1.4–20 kDa), non-ribosomally synthesized peptides and cyclic lipopeptides (0.8–42 kDa) and exopolysaccharides (>1000 kDa). Different bacteriocins act against Gram-positive or Gram-negative bacteria, fungal pathogens and amoeba cells. The main mechanisms of bacteriocin lytic activity include interaction of peptides with membranes of target cells resulting in structural alterations, pore-forming, and inhibition of cell wall biosynthesis. DNase and RNase activity for some bacteriocines are also postulated. Non-ribosomal peptides are synthesized by special non-ribosomal multimodular peptide synthetases and contain unnatural amino acids or fatty acids. Their harmful effect is due to their ability to form pores in biological membranes, destabilize lipid packaging, and disrupt the peptidoglycan layer. Lipopeptides, as biosurfactants, are able to destroy bacterial biofilms. Secreted polysaccharides are high molecular weight compounds, composed of repeated units of sugar moieties attached to a carrier lipid. Their antagonistic action was revealed in relation to bacteria, viruses, and fungi. Exopolysaccharides also inhibit the formation of biofilms by pathogenic bacteria and prevent their colonization on various surfaces. However, mechanism of the harmful effect for many secreted antibacterial substances remains unknown. The antimicrobial activity for most substances has been studied in vitro only, but some substances have been characterized in vivo and they have found practical applications in medicine and veterinary. The cyclic lipopeptides that have surfactant properties are used in some industries. In this review, special attention is paid to the antimycobacterials produced by B. licheniformis as a possible approach to combat multidrug-resistant and latent tuberculosis. In particular, licheniformins and bacitracins have shown strong antimycobacterial activity. However, the medical application of some antibacterials with promising in vitro antimycobacterial activity has been limited by their toxicity to animals and humans. As such, similar to the enhancement in the antimycobacterial activity of natural bacteriocins achieved using genetic engineering, the reduction in toxicity using the same approach appears feasible. The unique capability of B. licheniformis to synthesize and produce a range of different antibacterial compounds means that this organism can act as a natural universal vehicle for antibiotic substances in the form of probiotic cultures and strains to combat various types of pathogens, including mycobacteria.

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Section: Antibacterial Substances Secreted By Bacillus Lich...mentioning

confidence: 99%

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications

Shleeva,

Kondratieva,

Kaprelyants

2023

Pharmaceutics

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“…Only Ubenimex (bestatin), a drug inhibitor, is currently approved by the FDA for its uses in human pathologies, mainly in cancer [91]. Natural inhibitors of human and mammalian APN in general are scarce and have mainly been described from microorganisms [18,96], plants [97], marine invertebrates [36,48,98,99], and more recently from Cuban toad secretions [100,101] (Figure 12). Several compounds from marine organisms have been described with anticancer activities; however, very few of them have been linked with APN inhibition or interaction [102][103][104][105][106].…”

Section: Inhibitors Of Aminopeptidase N Isolated From Marine Organismsmentioning

confidence: 99%

Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families

et al. 2023

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Proteolytic enzymes, also known as peptidases, are critical in all living organisms. Peptidases control the cleavage, activation, turnover, and synthesis of proteins and regulate many biochemical and physiological processes. They are also involved in several pathophysiological processes. Among peptidases, aminopeptidases catalyze the cleavage of the N-terminal amino acids of proteins or peptide substrates. They are distributed in many phyla and play critical roles in physiology and pathophysiology. Many of them are metallopeptidases belonging to the M1 and M17 families, among others. Some, such as M1 aminopeptidases N and A, thyrotropin-releasing hormone-degrading ectoenzyme, and M17 leucyl aminopeptidase, are targets for the development of therapeutic agents for human diseases, including cancer, hypertension, central nervous system disorders, inflammation, immune system disorders, skin pathologies, and infectious diseases, such as malaria. The relevance of aminopeptidases has driven the search and identification of potent and selective inhibitors as major tools to control proteolysis with an impact in biochemistry, biotechnology, and biomedicine. The present contribution focuses on marine invertebrate biodiversity as an important and promising source of inhibitors of metalloaminopeptidases from M1 and M17 families, with foreseen biomedical applications in human diseases. The results reviewed in the present contribution support and encourage further studies with inhibitors isolated from marine invertebrates in different biomedical models associated with the activity of these families of exopeptidases.

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Bestatin and bacitracin inhibit porcine kidney cortex dipeptidyl peptidase IV activity and reduce human melanoma MeWo cell viability

Méndez

Arrebola

Valdés‐Tresanco

et al. 2020

International Journal of Biological Macromolecules

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Bacitracin is a non-competitive inhibitor of porcine M1 family neutral and glutamyl aminopeptidases

Cited by 8 publications

References 15 publications

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications

Marine Invertebrates: A Promissory Still Unexplored Source of Inhibitors of Biomedically Relevant Metallo Aminopeptidases Belonging to the M1 and M17 Families

Bestatin and bacitracin inhibit porcine kidney cortex dipeptidyl peptidase IV activity and reduce human melanoma MeWo cell viability

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