Antibacterial Agents Past and Future

Shimon E Shatzmiller^*, Marina Kovaliov, Galina Zats, M. & Inbal Lapidot

Department of Chemical Sciences, Ariel University, Israel

Shimon E Shatzmiller, Department of Chemical Sciences, Ariel University, Israel.

Keywords: Antibacterial; Drug Discovery; Microbe; Antibiotics; Antimicrobial Drugs

Abstract

The frequent failure of antibiotic treatment is an acute public health problem. The most apparent reason is that the development of bacterial resistance compromises the successful use of any therapeutic agent. An example is Aminoglycoside antibiotics, such as gentamicin and kanamycin, directly target the ribosome, yet the mechanisms by which these bactericidal drugs induce cell death are not fully understood. The era of antibiotics based on intracellular target components seem to end. Also, the era of antibiotics that hinder cell wall synthesis is losing momentum. The long list of antibiotic drugs to its families is becoming insufficient since it hardly answers the common bacterial infections acquired nonsocial or otherwise. It seems, that exploitation of the Antimicrobial Peptides. AMP, Examples include cecropins, from insects, magainins from amphibians and cathelicidins, from mammals, and their way to eradicate bacteria by cell wall disruption is one of the few clues to the problem of microbe’s resistance, eradication of persister cells, dormant cells and mutants may become a real option and bring remedy to those who suffer the incurable infection caused by those killer bacteria.
The antimicrobial peptides are nature’s weapon to combat the invasion of microbes as host defense agents, the first line of defense. However, the natural peptides suffer from serious drawbacks the first in the list is their being peptides and sensitive to enzymatic digestion. The approach of peptidomimetics [1] bears many advantages over the gift of nature, and that is:
1. Stability in the enzymatic world.
2. The option of human design.
3. Use of un-natural components to the construction of the mimetic architecture.
An approach based on those lines enables the introduction of the novel design of components that may aid in the eradication but are novel for nature. It may allow the exploration of the way of selective eradication of microbes in the presence of beneficial flora.
There are many obstacles in this way: It is needed to learn about the mechanisms in which the AMP disrupt the cell membranes in full detail. Today, many ways were found in which the membranes are destroyed. It was found that low molecular weight (MW = 500) non-peptide mimics can eradicate bacteria, and small structural modification may lead to preference in eradication at the will of either Gram-positive or Gram-negative bacteria. The ruthless selection for resistant bacteria, coupled with an insufficient investment in antibacterial research, has led to a steady decline in the efficacy of existing therapies and a paucity of novel structural classes with which to replace them or complement their use.
In This Chapter, we survey the antibacterial Agents situation with emphasis on the novel trend of developments based on antimicrobial peptides and their surrogates.

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