## 1 Introduction  
Antimicrobial resistance can occur naturally over time, typically through genetic changes. The process is, therefore, natural and inevitable [1]. However, the exponential increase in antimicrobial resistance has led to the endemic progression of infections and multidrug-resistant (MDR) phenotypes [2]. The antibiotics currently available for treating common infections are often inefficient. Therefore, alternative treatments must be identified [3]. Antimicrobial peptides (AMPs) represent an attractive option because they usually present a broad spectrum of activity, produce immunomododulatory effects, and can ward off resistance [4]. AMPs are now a small but growing category in the market. The antimicrobial peptide database contains more than 3400 molecules of different categories and biological sources [5]. Currently, a few AMPs are used mainly as a \"last resource\" treatment, for example, gramicidin, polymynxin, and daptomycin, while some are in clinical and pre-clinical evaluation, for example, nisin and LL-37 cathelicidin [6]. _Lactobacillus plantarum_, a Gram-positive bacterium widely distributed in nature, produces bacteriocins called \"plantaricins\". Bacteriocin peptides are an essential group of AMPs, synthesized by bacterial ribosomes, which interfere with the growth of other microorganisms for protection. Plantaricin A (PlnA), a 26-aminoacid length cationic peptide with membrane-permeabilizing properties, is one of the best-characterized members of this group [7]. Plantaricin 149 (Pln149), a second member of this group, obtained from the strain \(L\). _plantarum_ NRIC 149, shares the same N-terminal sequence as PlnA. Pln149 contains the sequence YSLQMGATAIKQVKKLFKKKGG and shows inhibitory activity against other lactobacillus. Its synthetic version, a C-terminal amidated peptide, showed meaningful action against \(S\). _aureus_ and _Listeria monocytogenes_[8]. Like PlnA, the synthetic analogs of Pln149 preserved their activity against pathogenic bacteria, even after removing the N-terminal pentapeptide [9]. The typical disorder-to-helix conformational changes observed in many linear cationic AMPs are also maintained. Attempts to optimize Pln149 included keeping the fluoreylmethyloxycarbonyl (Fmoc) protecting group in the N-terminal portion of the AMP. This change yielded significant, hitherto-unobserved findings, such as an improved action on Gram-positive bacteria, and promoted action on gram-negative bacteria [9]. The uptake of the Fmoc group is thought to be the reason for its more significant action in Gram-negative bacteria, which have an outer membrane absent in Gram-positive bacteria. In contrast, the solid hydrophobic action of Fmoc led to increased toxicity because it increased the interaction with zwitterionic phospholipids. Subsequently, the physicochemical mechanisms that occur during the interaction between the peptide and membrane models were elucidated [10]. This interaction depends on the negative electron charge density of the membrane, and can cause a disruptive effect. Adsorption on zwitterionic membranes has also been observed, which explains the action described in _Saccharomyces cerevisiae_. Factors other than charge seem to modulate the action of Pln149, such as curvature, lipid organization, and degree of hydration [11; 12]. These studies suggested that Pln149 acts carpet-like, in which the helices align parallel to the membrane surface [10; 13]. In this study, we present Pln149-PEP20 (Fmoc-KAVKKLFKKWG), an optimized molecule based on Fmoc-Pln149(6-22), which was designed as an amphipathic alpha helix to enhance antimicrobial activity and lower cytotoxicity. _Enterococcus ficeum_, _Staphylococcus aureus_, _Klebsiella pneumoniae_, _Acinetobacter baumannii_, _Pseudomonas aeruginosa_, and _Enterobacter_ spp. (ESKAPE) pathogenic bacteria were used as study models. ESKAPE bacteria are associated with the highest burden of MDR infections worldwide [14].