**3. Antimicrobial peptides and alternative antimicrobial agents**

The two major classes of alternate antimicrobial candidates are cationic, geneencoded antimicrobial peptides (AMPs) [30], and, π-conjugated oligo/polyelectrolytes [29]. Initial studies suggested that bacteria still find it difficult to show resistance against the second class of antimicrobial molecules [31].

The bounded ability to cross the bacterial cell membrane is the major limitation in the subsequent development of peptides as antimicrobial agents. To overcome this problem and achieve a more efficient cellular uptake, peptides and a delivery vector were combined in a single molecule. For this purpose, prolinerich antimicrobial peptides (PrAMPs), as a part of the innate immune response [32] via the inner membrane transporters SbmA and MdtM are transported into a large panel of Gram-negative bacterial cells. Results showed that PrAMPs could be suitable carriers to transfer the other non-penetrating AMPs into the bacterial cells [33, 34]. According to this, PrAMPS are considered as a novel class of antibiotics [32–35].

Antimicrobial peptides (AMPs) are one of the most promising candidates for a novel class of antibiotics [36]. Antimicrobial peptides (also called host-defense peptides) occur in nature as an ancient class of polypeptides [37]. AMPs are part of the innate immune system and exhibit antibacterial activity against Gram-negative and Gram-positive bacteria. According to this, AMPs serve as templates for the design of new antibacterial agents against multidrug resistance. Gramicidin and defense are natural AMPs that were discovered at the beginning of the twentieth century [38]. Today, lots of cationic AMPs are known to permeabilize real bacterial membranes [39]. After the emergence of antimicrobial-resistant bacteria, AMPs were considered as potential antibiotic drugs. The advantages of AMPs over conventional antibiotics and exigent need for the development of novel antibiotics lead to the upsurge of AMP research and their clinical trials activity in recent years [36]. In addition, synthetic AMPs or a variety of peptidomimetic antimicrobials have been very investigated to overcome the inherent drawbacks (e.g., stability) of peptides in physiological conditions [7].

Antimicrobial peptides have terrific chemical diversity and are based on some common structural characteristics set apart from traditional antibiotics. AMPs generally contain less than 100 amino acids, most of them including positively charged residues, such as lysine, arginine, and histidine, and more than 50% of them have a large portion of hydrophobic. In addition to the structural differences, AMPs directly target the bacterial cell membrane in most cases. Antimicrobial peptides based on their structure are classified into four different groups—α-helical, β-sheet, extended, and cyclic. For example, while some AMPs consist of a single helix or sheet entirely, others have a more complicated structure. The extended peptides are characterized by non-recognizable structural motifs and consist of specific amino acids, such as arginine, tryptophan, glycine, and histidine [40].

Natural antimicrobial peptides isolated are effective against Gram-positive and Gram-negative bacteria, enveloped and non-enveloped viruses, yeasts, fungi, molds, and parasites [41]. A single AMP may not be effective against all pathogens, however, may exhibit the same antimicrobial activity between different germs with anionic membranes. In addition, due to their mechanism of action, some isolated AMPs from natural sources can display species-specific antimicrobial activity [42]. This may be an outcome of a highly specialized environmental niche and evolutionary advantage that specific antimicrobial peptides present for survival [41]. As many antimicrobial peptides act on lipid components of the bacterial cell membrane, they often demonstrate broad-spectrum antimicrobial activity [43].

*Antibiotic Resistance among* Escherichia coli *Isolates, Antimicrobial Peptides and Cell Membrane… DOI: http://dx.doi.org/10.5772/intechopen.101936*
