Journal
CURRENT GENETICS
Volume 68, Issue 1, Pages 83-90Publisher
SPRINGER
DOI: 10.1007/s00294-021-01217-9
Keywords
Non-lytic antimicrobial peptides; Bacteria penetrating peptides; Antimicrobial antisense agents; Bacterial membranes
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Funding
- Novo Challenge Center for Peptide-Based Antibiotics grant [NNF16OC0021700]
- Villum Fonden [35894, 36297]
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With the increase in multidrug-resistant pathogenic bacteria, the development of novel antimicrobials, including antimicrobial peptides and antimicrobial antisense agents, has become a focus of research. Non-lytic AMP and BPP-PMO/PNA conjugates are able to translocate across the cytoplasmic membrane via receptor-mediated transport, showing promising potential as new antibacterial agents.
The increase in multidrug-resistant pathogenic bacteria has become a problem worldwide. Currently there is a strong focus on the development of novel antimicrobials, including antimicrobial peptides (AMP) and antimicrobial antisense agents. While the majority of AMP have membrane activity and kill bacteria through membrane disruption, non-lytic AMP are non-membrane active, internalize and have intracellular targets. Antimicrobial antisense agents such as peptide nucleic acids (PNA) and phosphorodiamidate morpholino oligomers (PMO), show great promise as novel antibacterial agents, killing bacteria by inhibiting translation of essential target gene transcripts. However, naked PNA and PMO are unable to translocate across the cell envelope of bacteria, to reach their target in the cytosol, and are conjugated to bacteria penetrating peptides (BPP) for cytosolic delivery. Here, we discuss how non-lytic AMP and BPP-PMO/PNA conjugates translocate across the cytoplasmic membrane via receptor-mediated transport, such as the cytoplasmic membrane transporters SbmA, MdtM/YjiL, and/or YgdD, or via a less well described autonomous process.
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