*3.1.3 Loss of homeostasis by metal ions*

The balance of metallic elements is essential for microbial survival, since it regulates metabolic functions by helping coenzymes, cofactors and catalysts. When the bacteria have an excess of metals or metal ions, there will be a disorder in the metabolic functions. Metal ions bind with DNA and alter the helical nature by cross-linking between and within the DNA strands. The metal ions neutralize the charges in LPS and increase the permeabilization of the outer membrane. The ions of metal oxides might also cause the decomposition of bacterial cells due to the diffusion of metal ions by generating large amounts of hydroxyl radicals and diffusion in bacterial cells. Other studies indicate that NPs of metal oxides slowly release metal ions through adsorption, dissolution and hydrolysis; they are toxic and abrasive to bacteria and, therefore, lyse the cells.

#### *3.1.4 Dysfunction of proteins and enzymes*

Protein dysfunction is another mode of antibacterial activity exhibited by NPs of metal oxides. The metal ions catalyze the oxidation of the side chains of amino acids resulting in carbonyls bound to proteins. The carboxylation levels within the protein molecule serve as a marker for the oxidative damage of the protein. This carboxylation of proteins will lead to the loss of catalytic activity in the case of enzymes, which finally triggers the degradation of proteins.

#### *3.1.5 Inhibition of the transduction signal*

Electrical properties of metal oxide NPs interact with nucleic acids inducing suppress of cell division by altering processes of replication of the chromosomal DNA and the plasmid in microorganism. It is known that signal transduction in bacteria is affected by NPs of metal oxide. Phosphotyrosine is an essential component of mechanism of signal transduction in bacteria. NPs dephosphorylate

the phosphotyrosine residues, which inhibits signal transduction and, ultimately, obstructs growth of bacteria.
