Editorial: Advancing Antimicrobial Strategies – Nucleic Acid and Peptide-Based Approaches

Nuno F Azevedo^1*Sybil Obuobi²Dai Thien Nhan Tram³Peter E. Nielsen⁴

• ¹Faculty of Engineering, University of Porto, Porto, Portugal
• ²UiT Norges arktiske universitet, Tromsø, Norway
• ³National University of Singapore, Singapore, Singapore
• ⁴Kobenhavns Universitet, Copenhagen, Denmark

Most of the original research papers in this Research Topic are related to pep de-based approaches, which is likely a reflec on of the higher number of research groups working with these molecules. Giugliano et al. reported the use of pan nins (isolated from Pandinus imperator scorpion venom) as a promising class of pep des which exert a membranoly c an microbial ac on against various clinical isolates of Klebsiella pneumoniae. This same microorganism was used as a target for 8 different pep des of human, insect or synthe c origin (Hanstein et al). In another study, the D-Bac8c 2,5 Leu pep de was shown to significantly reduced the viability of monospecies and polymicrobial biofilms of Staphylococcus aureus and Pseudomonas aeruginosa (Shahrour et al). Furthermore, D-Bac8c 2,5 Leu loaded hydrogel formula ons provided sustained drug release and an enhanced an microbial ac vity. Another pep de, bacillomycin D, isolated from Bacillus amyloliquefaciens, also showed potent ac vity against the fungal pathogen Fusarium graminearum (Liu et al). In a related work, another an microbial lipopep de and phytohormone complex powder prepared from B. amyloliquefaciens was also assessed for an microbial ac vity, aiming at treatment of Citrus Huanglongbing (HLB) disease (Ding et al.). Two strategies were assessed against extensively drug-resistant (XDR) gram nega ve pathogens. The first one involved a novel class of anthrocolins, with potent an microbial ac vi es reported to interfere with the amino acid metabolism in Pseudomonas aeruginosa (Yang et al), and another comprising the synergis c ac on between pep de-neomycin conjugates and polymyxin B (Story et al.).In addi on, two papers in this collec on describe advances in nucleic acid-based approaches. In one of them, engineered hammerhead ribozymes were directed against the mRNA of an essen al gene of Escherichia coli (Miszkiewicz-Golec et al). This promising approach allowed to inhibit bacterial growth by up to 70% over 24 h and enhance tetracycline efficacy 2-to 4fold. To assess their ac on, ribozymes were incorporated into bacterial plasmidsfor future applica ons a direct delivery of ribozymes to the bacteria s ll needs to be devised. In another study, Mendez et al. evaluated whether an sense phosphorodiamidate morpholino oligomers retain ac vity against biofilm of the Burkholderia cepacia complex (Bcc). The same oligomers were previously conjugated with a pep de for delivery into the bacterial cell and shown to be ac ve against planktonic bacteria. Using the same strategy, the authors concluded that the oligomer delivery and an microbial ac vity are s ll present to some extent in the context of biofilms. In the future, in vivo studies should be performed to understand if these oligomers could become viable alterna ves for the treatment of condi ons such as pulmonary Bcc infec ons.Finally, this Research Topic also includes two reviews. One review from Wojciechowska describes the applica on of endolysins, bacteriophage-encoded pep doglycan hydrolases, and membrane-ac ve pep des as next-genera on an bacterial agents against Gram-nega ve bacteria; while another by Su et al provides a general overview on an microbial pep des, including their original source (e.g. animal or plant-derived), as well as their structure, op miza on strategies and main applica ons.Collec vely, these studies highlight the poten al of nucleic acid and pep de-based strategies in addressing resistant strains or polymicrobial infec ons via unique mechanisms, and will certainly assist in tackling the rise of an microbial resistance. We would like to thank the authors and co-authors of this research topic for their valuable contribu ons in this field, and hope that the readers will enjoy this collec on of ar cles.