The extensive use and misuse of antibiotics in medicine result in the emergence of multidrug-resistant bacteria, creating an urgent need for the development of new chemotherapeutic agents. Nowadays, antimicrobial peptides are widely recognized as a class of promising candidates with activity against multidrug-resistant bacteria. NK-18 is a truncated peptide derived from NKLysin, an effector of cytotoxic T cells and natural killer cells. In this study, we studied the antibacterial mechanism of action of NK-18. The results revealed that NK-18 has potent antibacterial activity against Escherichia coli and Staphylococcus aureus. According to our findings, NK-18 is membrane active and its target of action is not only the bacterial membrane but also the DNA in the cytoplasm. The double targets of NK-18 make it difficult for bacteria to generate resistance, which may present a new strategy to defend against multidrug-resistant bacteria and provide a new lead in the design of potent antimicrobial peptides with therapeutic application in the presence of increasing resistance to conventional antibiotics.
In recent decades, the misuse of conventional antibiotics has resulted in the emergence of many multidrug-resistant strains (1-3). With the increasing severity of this phenomenon, such strains have become a serious menace to human health and quality of life. Therefore, development of a new class of antibiotics with mechanisms of action different from those of conventional antibiotics is becoming more and more urgent and critical. The outbreak of superbugs in several countries in the world in 2011 emphasized once again the need to search for and develop new antimicrobial agents or resources. Nowadays, it is widely recognized that antimicrobial peptides (AMPs) could play a promising role in the fight against multidrug-resistant strains. AMPs are considered a new class of antibiotic with characteristics including an ability to kill target cells rapidly, an unusually broad spectrum of activity, and activity against some of the more serious antibiotic-resistant pathogens in the clinic. Furthermore, the selection of mutants resistant to AMPs in vitro is relatively difficult (4-6).AMPs are widespread in nature, including microorganisms, insects, invertebrates, amphibians, plants, birds, and mammals (7,8). They comprise a wide range of short, cationic peptides which constitute the first line of innate immune defense against infectious agents (9-12). To date, more than 1,800 AMPs have been purified from a wide range of organisms (13) or chemically synthesized on the basis of the sequences of purified peptides. NK-18 is a derivative of a mammalian protein, NK-lysin. It derives from the core region of NK-lysin (residues 39 to 56) and possesses potent antitumor activity against prostate and bladder tumors with a membrane-active mode of action (14). The amino acid sequence of NK-18 is KILRGVCKKIMRTFLRRI-NH 2 . Compared with NK-lysin, NK-18 has the potential to be used clinically because of its shorter amino acid sequence and lower cos...