RHA™ anti-Ampicillin monoclonal antibody, clone amp

Ampicillin (AMP), as a class of antibiotics used primarily for the prevention and treatment of a variety of bacterial diseases, is one of the most important β-lactam antibiotics available today and the first broad-spectrum penicillin used to treat Enterobacteriaceae infections. Antibiotics have affinity for a wide range of molecular targets and can affect various properties of target cells. The first-generation antibiotic, penicillin G, was discovered by Aleksander Fleming and put into clinical use in 1943. AMP, a β-lactam drug, contains a β-lactam ring in its molecular structure. The ring is a four-membered ring with a carbonyl group. The structure of the square ring exhibits a higher internal tension than that of the common five- or six-membered rings. Furthermore, the carbonyl group provides an optimal nucleophilic attack site for hydrolysis. In addition, the structural features of the β-lactam ring provide higher reactivity for β-lactam antibiotics to inactivate penicillin-binding proteins (PBPs).

Figure 1. Structuresof (A) β-lactam ring and (B) AMP
(Source: Gawrońska M, et al. 2022)

Peptidoglycan constitutes the cell wall of the bacteria, in the presence of transglycosidase, the sugar chains of the peptidoglycan undergo cross-linking, whereby the peptide chains extend from the sugars in the polymer and form a cross-link from one peptide to another. In the presence of PBPs, the D-alanyl-alanine portion of the peptide chain cross-links with glycine residues, and this cross-linking enhances the cell wall. The primary targets of β-lactams are PBPs, β-lactam rings that mimic the D-alanyl D-alanine portion of the peptide chain that normally binds to PBPs. Due to the interaction of PBPs with the β-lactam ring, the bacterial cell wall is unable to synthesize new peptidoglycan, and the destruction of peptidoglycan leads to bacterial lysis.

Figure 2. β-Lactams acting on peptidoglycan
(Source: Kapoor G, et al. 2017)

AMP may affect human health through allergic reactions, breathing difficulties and seizures. Clinical misuse of antibiotics has led to the emergence of many drug-resistant strains of bacteria that significantly reduce the original clinical efficacy of antibiotics. With the emergence and rapid growth of multidrug-resistant strains, in the future we may need to face situations where minor infections become deadly threats. Bacteria can defend themselves against antibiotic damage by adjusting their outer membrane permeability, thereby reducing antibiotic uptake or increasing their efflux. For example, β-lactams can only cross the outer membrane through pore proteins, and a reduction in the number of porin channels leads to a decrease in the number of β-lactam antibiotics entering the cell, resulting in resistance to these antibiotics. However, the development of new antibiotics against drug-resistant bacteria is a slow process, with the number of emerging antibiotics decreasing and a portion of previously effective antibiotics no longer able to meet the needs of clinical therapy due to the emergence of resistant bacteria. Therefore, researchers have made various modifications to the original antibiotic structure with a view to improve the antimicrobial properties and bioavailability.

anti-AMP monoclonal antibody