Capsicum spp. (hot
peppers) demonstrate a range
of interesting bioactive properties spanning anti-inflammatory, antioxidant,
and antimicrobial activities. While several species within the genus
are known to produce antimicrobial peptides (AMPs), AMP sequence mining
of genomic data indicates this space remains largely unexplored. Herein,
in silico AMP predictions were paired with peptidomics to identify
novel AMPs from the interspecific hybrid ghost pepper (Capsicum
chinense × frutescens). AMP prediction
algorithms revealed 115 putative AMPs within the Capsicum
chinense genome, of which 14 were identified in the aerial
tissue peptidome. PepSAVI-MS, de novo sequencing, and complementary
approaches were used to fully molecularly characterize two novel AMPs,
CC-AMP1 and CC-AMP2, including elucidation of a pyroglutamic acid
post-translational modification of CC-AMP1 and disulfide bond connectivity
of both. Both CC-AMP1 and CC-AMP2 have little homology with known
AMPs and exhibited low μM antimicrobial activity against Gram-negative
bacteria, including Escherichia coli. These findings
demonstrate the complementary nature of peptidomics, bioactivity-guided
discovery, and bioinformatics-based investigations to characterize
plant AMP profiles.
The Antarctic sponge Dendrilla antarctica is rich in defensive terpenoids with promising antimicrobial potential. Investigation of this demosponge has resulted in the generation of a small chemical library containing diterpenoid secondary metabolites with bioactivity in an infectious disease screening campaign focused on Leishmania donovani, Plasmodium falciparum, and methicillin-resistant Staphylococcus aureus (MRSA) biofilm. In total, eleven natural products were isolated, including three new compounds designated dendrillins B–D (10–12). Chemical modification of abundant natural products led to three semisynthetic derivatives (13–15), which were also screened. Several compounds showed potency against the leishmaniasis parasite, with the natural products tetrahydroaplysulphurin-1 (4) and dendrillin B (10), as well as the semisynthetic triol 15, displaying single-digit micromolar activity and low mammalian cytotoxicity. Triol 15 displayed the best profile against the liver-stage malaria parasites, while membranolide (5) and dendrillin C (11) were strong hits against MRSA biofilm cultures.
Traditional medicinal plants are rich reservoirs of antimicrobial agents, including antimicrobial peptides (AMPs). Advances in genomic sequencing, in silico AMP predictions, and mass spectrometry-based peptidomics facilitate increasingly highthroughput bioactive peptide discovery. Herein, Amaranthus tricolor aerial tissue was profiled via MS-based proteomics/peptidomics, identifying AMPs predicted in silico. Bottom-up proteomics identified seven novel peptides spanning three AMP classes including lipid transfer proteins, snakins, and a defensin. Characterization via top-down peptidomic analysis of Atr-SN1, Atr-DEF1, and Atr-LTP1 revealed unexpected proteolytic processing and enumerated disulfide bonds. Bioactivity screening of isolated Atr-LTP1 showed activity against the high-risk ESKAPE bacterial pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter cloacae). These results highlight the potential for integrating AMP prediction algorithms with complementary -omics approaches to accelerate characterization of biologically relevant AMP peptidoforms.
Acinetobacter baumannii
is a formidable opportunistic pathogen that is notoriously difficult to eradicate from hospital settings. This resilience is often attributed to a proclivity for biofilm formation, which facilitates a higher tolerance toward external stress, desiccation, and antimicrobials.
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