## 1 Introduction  
Overwhelming pathogenic stimuli can lead to the progression of host immune response to systemic inflammatory response syndrome (SIRS), increasing the severity of infections and ultimately inducing pathological processes of sepsis. Sepsis is a multifaceted syndrome caused by an aberrated immune response to bacterial infections, thereby culminating in excessive inflammation, organ dysfunction, and even death [1; 2]. According to a nationwide cohort study, the incidence of sepsis cases in Korea has increased, with approximately 233.6 per 100,000 people affected and a 22.6% mortality in 2016 [3]. Especially, infections by gram-negative bacteria are an urgent problem because the outer cell membrane of bacteria consists of lipopolysaccharideacharide (LPS), which not only triggers aberrant cascades of the inflammatory response but also hinders development of new antibiotics against resistant infections [4; 5]. Several studies have revealed that the disproportionate activation of toll-like receptors (TLRs) by invading pathogen or pathogenic molecules, such as LPS, Pam2 CSK4, or Pam3 CSK4, plays a vital role in sepsis pathogenesis [6; 7]. Despite dramatic advances in sepsis pathophysiology and treatment procedures, resuscitative strategies for gram-negative sepsis have not been approved to date. Therefore, the search for a novel class of antibiotic agents that can combat and overcome resistant events related to sepsis is urgently required. Numerous bioactive natural peptides from various organisms play a beneficial role either directly or indirectly in human physiology including antimicrobial and immunomodulatory activities [8; 9]. In all species of life, antimicrobial peptides (AMPs) form a component of the innate immune defense. AMPs show broad spectrum potential as small molecule antibiotics [10; 11; 12]. Persistent infection has resulted in living organisms evolving many host defensive mechanisms against pathogens, including transcription of AMP encoding genes [13]. With over four decades of peptide research, AMPs have emerged as an alternative class of naturally occurring antibiotics. Because AMPs have diverse structures and modes of action with broad spectrum antibacterial activities, development of novel AMPs is a promising strategy for combating multidrug-resistant (MDR) bacteria [14; 15]. Till date, more than 3000 AMPs have been identified but only seven have been approved by the U.S. Food and Drug Administration (FDA); these include colistin, gramicidin D, daptomycin, vancomycin, oritavancin, dalbavancin, and telavancin, which are either in the market or under clinical development [16; 17]. They have different structures and sequence motifs but share a broad spectrum of antibiotic actions. Although the detailed mechanisms underlying the antibacterial activity of AMPs have not been completely understood, they appear to involve transmembrane pore formation or intracellular killing [18]. Colistin is a well-studied antimicrobial cyclic peptide that targets gram-negative bacteria by binding to the negatively-charged LPS layer in the outer membrane and by causing cell death [19]. Besides antimicrobial properties, colistin has been shown to exhibit LPS-degradative and immunomodulatory effects. However, applications of colistin are limited because of its adverse effects [20]. Cathelicidins are another type of AMP that proteolytically activates in response to bacterial infection; they affect the permeability of the bacterial membrane and exhibit bactericidal effects [21]. Cathelicidin-derived LL-37 peptides can promote LPS neutralization and phagocytosis and exhibit immunomodulatory effects by skewing macrophage differentiation toward pro-inflammatory phenotypes [22; 23; 24]. Furthermore, proteolytic cleavage of LL-37 fragments could trigger additional inflammatory disorders [25]. Thus, controlling selectivity, improving stability, and reducing cytotoxicity-mediated adverse effects are the prime strategies to design potent AMPs.