**3. Alternative to antibiotic therapy**

## **3.1 Spread of antibiotic resistant**

#### *3.1.1 Antimicrobial peptides*

Antimicrobial peptides or host defense peptides are biologically active molecules produced by variety of organisms [62]. AMPs have board spectrum of antimicrobial activity against pathogenic microorganisms and are the first line defense against the foreign attacks [63]. AMPs also serve as immune-modulators in higher animals [64]. AMP'S are expressed by specific genes and their expression is by either constitutive or specific external factors [64]. AMPS are classified into several types based on the source, activity Amino acid sequences and structural characteristics. AMPS are usually 1. Cationic and Hydrophophic in nature with helical polypeptides of short amino acid sequences mostly lysine and arginine amino acids. 2. Some are Cationic and Amphiphilic (Both hydrophobic and Hydrophilic).

#### *3.1.2 Membrane target mechanism*

Amphiphilic peptides are alpha helix and their amphiphilicity interacts with bacterial cell membrane. These alpha helices peptides are folded and adsorbed with both hydrophilic and hydrophobic sides of lipid bilayer membranes. Positive charged AMPS interact with negative charged cell membranes by electrostatic interactions and undergo conformational changes of the cell membrane.

#### *3.1.3 Non membrane target mechanism*

AMPS bind to hydrophobic and negative charged cell membrane of lipid bilayer at their N-terminal ends containing basic amino acids and their C-terminal ends are amidated with neutral hydrophobicity. The number of positive net charge are related to the antibacterial activity and their hemolytic activity is related to the hydrophobicity of the peptides. Multiple models to explain the action of these peptides, include the toroidal pore model, the barrel-stave model, and the carpet model etc. [65].

#### *3.1.4 Advantages of AMPs*

1.AMPs have rapid germ killing abilities with low bactericidal concentration

*Antibiotic Resistant* Staphylococcus aureus *DOI: http://dx.doi.org/10.5772/intechopen.100057*

2.No toxic effects

3.Hard to induce bacterial resistance

4.AMPs have broad spectrum antimicrobial activity

5.AMPs have good thermal stability and good water stability

6.AMPs are small molecules with low synthetic cost

7.AMPs show inhibitory ability to cancer cells [66].

*3.1.5 Disadvantage of AMPs*

AMPs have mostly L-amino acids; are sensitive to protease degradation and rapid renal clearance.

AMPs are not specific to microorganisms and display systemic toxicity

Oral administration of AMPS can lead to proteoloytic degradation by gastric enzymes such as trypsin and pepsin.

Systemic administration results in short half life time in vivo and cytotoxicity in blood

Chemical modification of AMPS and the use of drug delivery vehicles such as Nanoparticles, lipid system can improve the properties of AMPS for their clinical use [26].

#### **3.2 Nanoparticles**

Nanoparticles are smaller in size (less than 10 nm in diameter) that exhibit high surface area to volume ratio [27]. Nano particles have significant application in the medical fields. Nano-drugs or Nanoparticles can act individually or synergistically with antibiotic components against the multi-drug resistant pathogens. Nanoparticles are used as drug delivery vehicle that improve the therapeutic efficacy and enhance their physicochemical characteristics [28]. Metal and metal oxide Nanoparticles such as gold, silver, titanium, copper, zinc etc. are the most studied Nanoparticles against the multi-drug resistant pathogens [28].

#### *3.2.1 Interaction and penetration of nanoparticle to bacteria*

Electric charges present on the nanoparticles are the most important property in terms of antimicrobial effect. Interactions of nano-particles with bacteria membrane depend on the different factors such as electrostatic interactions, hydrophobic interactions, receptor ligand interaction and Van der Val forces [29].

The phosphates present in the teichoic acids of gram positive bacterial cell wall are responsible for bacterial negative charge and acts as binding site of divalent cation ions. Gram Negative bacteria consists of plasma or cytoplasmic membrane followed by peptidoglycan layer and hydrophobic lipid bilayer consisting of lipopolysaccharides (Phosphates and Carboxylates) which are responsible for negative charge of gram negative bacterial cell wall. The interaction of NPs with membrane structure leads to blebbing, tubule formation and other membrane defects [67].

Nanoparticles can bind to cell wall by electrostatic interactions and disrupt cytoplasmic membrane leading to leakage of cytoplasmic content of the bacterial cell. Nano particles also bind to intracellular components such as DNA and other enzymes responsible for normal cellular machinery causing disruption in cellular machinery by creating oxidizing stress, electrolytic imbalance and enzyme inhibition followed by cell death. For example, free copper ions (CU2+) from CU Nanoparticles generates reactive oxygen species that disrupts the amino acid synthesis and DNA [67].
