Zinc Immunology and Zn2+ Ions Binding Anti-Bacterial Vaccine Activity for Bacterial Cell Walls against Gram-Positive and Gram-Negative Bacteria

Zinc homeostasis during acute phase response is the temporal transfer of serum zinc to the tissues, causing transient serum hypozincemia, which is rebalanced during resolution of the inflammatory response. Bacteria have to avoid recognition by the host immune system in order to establish a succesful infection which bacterial autolysins enable the bacteriolyses of bacterial cell walls trim cell surface PGN to prevent detection by bacterial innate immune system.

The bacterial cell walls are remodeled by PGN synthesis and PGN autolysin. S.aureus amidase AmiA shed light on PGN binding and cleavage that amiA distinguishes PGN mostly by the peptide, and cleavage is facilitated by a zinc-activated water molecule, developing new therapeutics against MRSA.The autolytic activity of the recombinant amidase of the Aas (autolysin/adhesin of Staphylococcus saprophyticus) is inhibited and is neccesary for the C-terminal GW repeats, not the N-terminal repeats. AmiB catalyzes the degradation of PGN in bacteria, resulting in a marked increases of sensitivity to oxidative stress and organic acids. Amidase activity of amiC controls cell ceparation and PGN fragments release. In these autolysins, zinc-dependent PGN autolysin of amidases may be enhanced and induced anti-bacterial vaccine activities.

Autolysin-mediated lysis-induced bacterial cell death can contribute to the bactericidal vaccine activities. Lytic amidase autolysin LytA associates with the cell wall via its zinc-binding motif. The LytB PGN hydrolase responsible for physical separation of daughter cells cleaves the GlcNAc-β-(1,4)-MurNAc glycosidic bond of PGN building units. LytC, LytD, and LytF are expressed in the same subpopuration of cells and complete flagellar synthesis. Major Atl autolysin also have an essential role in the early events of the fibronectin-binding proteins (FnBPs)-dependent S.aureus biofilm phenotype.

Human peptidiglycan recognition proteins (PGLYRPs) are novel class of recognition and effector molecules with broad Zn2+-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria. It has been clear that the D-glutamate is effective for community accquired MRSA, and the other, it is efficient for P. aeruginosa PA14.

Adsoption of Zn2+ ions to the bacterial cell surface increases cell wall cohesion and favors the projection of elongated S. aureus surface protein (SasG) away from the cell surface. Zinc is an essential nutrient for microbial growth, but can be toxic in excess. Zinc importer adcABC of the primary group A streptococcus (GAS) zinc uptake system is composed of a cell surface-exposed zinc-binding protein (adcA), an inner membrane permease(AdcB), and a cytosolic ATPase (AdcC) that provides the energy for zinc import by ATP hydrolysis.

Enterotoxigenic E.coli (ETEC) is the most common bacerial cause of children’s diarrea, in which antigen and antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea, and polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. Oral vaccines which are intended for global use do not necessarily induce the same immune responses in all children worldwide. Zinc has positive effect in children with complication of diarrhea that young children are immunized.