**2. β-Lactam antibiotics (β-LA)**

The landmark discovery the beta-lactam penicillin has been developed with the remarkable weapon to control bacterial infections during the Second World War [18]. It was naturally synthesized from *Penicillium chrysogenum* (also known as *Penicillium notatum*). Penicillin G was the first β-lactam antibiotic (β-LA) discovered in 1944, which began the era of antibiotics against a wide range of infectious microorganisms [19]. The development of penicillin led to search its different derivatives (amoxicillin and methicillin) for the betterment of their efficacy, bioavailability, solubility, stability, and other pharmacokinetic properties and to evade steadily emerging problem of multidrug resistance (MDR). Structurally, penicillin is composed of a thiazolidine ring attached to a side chain of a four-membered betalactam ring. All penicillins are derivatives of 6-aminopenecillinic acid, which sometimes differ in their side-chain structure. Many β-LA have lactam ring as an integral part of a molecule such as cephalosporins, monobactams, cephamycins, and the carbapenems (imipenem and meropenem). These β-LA antibiotics came into the light to rescue mankind from different Gram –ve and Gram +ve bacterial infections including *S. aureus*. β-LA are the most available and over 34 β-LA approved by the FDA, which together constitute ~50% of all antibiotic prescriptions worldwide. Now, β-LA share the annual consumption of over \$15 billion, which contribute almost 65% of the total antibiotics [20].

The β-LA primarily target the cell wall of a bacterial pathogen. Peptidoglycan or murien present in the cell wall provides the mechanical strength to the bacterial cell membrane, which is composed of an alternating unit of *N*-acetylglucosamine (NAG) and *N*-acetylmuramic acid (NAM) residues, joined together by β-1 → 4 linkage. The NAM is further linked with a pentapeptide stem, which is composed of L-Ala-D-Glu- L-Lys-D-Ala-D-Ala. The order and type of amino acids are almost similar in Gram –ve and Gram +ve bacterial with some slight variations. The last D-Ala is lost during maturation and glycan assembly is cross-linked to form a bridge with the carboxyl group of D-Ala at position 4 and the amino group of the amino acid at position 3. Mechanistically, β-LA acts upon a 4-membered "beta-lactam" ring, which shows a resemblance to D-Ala-D-Ala sequence of the cell wall [21]. The primary function of PBP is in the elongation of the cell wall, which is composed of two distinct components termed as PBP1–4. The radioactive analysis revealed that penicillin specifically interacts with PBP protein *via* covalent interactions [22]. The tight binding of β-LA to the transpeptidase domain of PBP (penicillin-binding protein) thereby inhibits the peptidoglycan synthesis by acylating transpeptidase, involved in crosslinking peptide to form peptidoglycan [23].
