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Abstract
Antibiotic resistance is an escalating, worldwide problem. Due to excessive use of antibiotics, multidrug-resistant bacteria have become a serious threat and a major global healthcare problem of the 21st century. This fact creates an urgent need for new and effective antimicrobials. The common strategies for antibiotic discovery are based on either modifying existing antibiotics or screening compound libraries, but these strategies have not been successful in recent decades. An alternative approach could be to use gene-specific oligonucleotides, such as peptide nucleic acid (PNA) oligomers, that can specifically target any single pathogen. This approach broadens the range of potential targets to any gene with a known sequence in any bacterium, and could significantly reduce the time required to discover new antimicrobials or their redesign, if resistance arises. We review the potential of PNA as an antibacterial molecule. First, we describe the physicochemical properties of PNA and modifications of the PNA backbone and nucleobases. Second, we review the carriers used to transport PNA to bacterial cells. Furthermore, we discuss the PNA targets in antibacterial studies focusing on antisense PNA targeting bacterial mRNA and rRNA.
Highlights
Excessive use of antibiotics has led to an alarming situation when many bacterial strains developed resistance to these antibiotics
The most effective way of transporting peptide nucleic acid (PNA) to bacteria was by cell penetrating peptides (CPP), (Figure 5) [105]
The use of sequence-specific oligonucleotides binding to natural nucleic acid targets has been a matter of extensive research, leading to a few FDA-approved oligonucleotide-based therapies in humans [152]
Summary
Excessive use of antibiotics has led to an alarming situation when many bacterial strains developed resistance to these antibiotics. Antisense oligonucleotides, used to inhibit the synthesis of proteins essential for bacteria to sustain life, may be helpful in the fight against bacterial infections. One such oligonucleotide is the peptide nucleic acid (PNA) molecule that combines the properties of both peptides and nucleic acids. A few reviews on PNA antibacterial applications have been published, e.g., [14,15,16,17,18] We have updated this information, focusing on PNA modifications, structural data for PNA-involving complexes, antibacterial targets, and transport into bacterial cells
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