The β-lactams retain a central place in the antibacterial armamentarium. Extensive use of β-lactams has led to the emergence and dissemination of resistance. Resistance can occur by multiple mechanisms, including modification of the target, reduction in cell permeability through downregulation of porins required for β-lactam entry, over-expression of efflux systems, and production of modifying or degradative enzymes. In the case of β-lactams, enzyme-mediated resistance arises from the activity of β-lactamases that hydrolyze the β-lactam amide. Therefore, some β-lactamases play a crucial role in the resistance of pathogens to β-lactam antibiotics.
β-lactamases are enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams, and carbapenems. β-Lactamases divide into four classes; the active-site serine β-lactamases (classes A, C and D) and the zinc-dependent or metallo-β-lactamases (class B). β-lactamase provides antibiotic resistance by breaking the antibiotics’ structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a β-lactam ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule’s antibacterial properties. Thus, β-lactam antibiotics can target a broad spectrum of gram-positive and gram-negative bacteria. For example, Clavulanic acid is an irreversible inhibitor of class A enzymes that have the potential for the research of infections by β-lactamase-producing organisms.
Sulbactam (CP45899) is a competitive, irreversible beta-lactamase inhibitor.
Sulbactam is a semi-synthetic penicillinate sulfone. Importantly, Sulbactam can inactivate β-lactams such as penicillin and cephalosporin. It is also active against Bacteroides and certain chromosomally mediated enzymes of Gram-negative bacteria. Meanwhile, Sulbactam itself contains a beta-lactam ring and has weak antibacterial activity by inhibiting penicillin-binding proteins. However, sulbactam in combination with other potential antibiotics exhibits activities against multidrug-resistant Acinetobacter baumannii infections.
All in all, Sulbactam (CP45899) is a competitive, irreversible beta-lactamase inhibitor that has the potential for the research of a variety of susceptible bacterial infections.