**4. Mechanism of β-lactam resistance in** *S. aureus*

Different mechanisms of drug resistance in bacterial pathogens are the major hurdle in their treatment. With emerging resistance, it became a serious concern to look into drug resistance mechanism, which can help us to prescribe a specific medication to effectively overcome the problem of resistance.

Several biochemical mechanisms are responsible for β-LA resistance, including enzymatic (β-lactamase) production inactivation of the drug (drug inactivation), modifications of drug target in penicillin-binding protein (PBPs) (target modifications), limiting uptake of drug by biofilm formation (reduced drug uptake), and active efflux of the drug (drug efflux) as shown in **Figure 1** [27, 28]. Bacterial pathogens resist the inhibitory action of antibiotics primarily due to the presence of an enzyme that inactivates the antibiotic or modified antibiotic target by mutation or by the post-translational mechanism, which reduces binding of the antibiotic to the target or bypass of the function dependent on the antibiotic target by an alternative enzyme that is not inhibited by the antibiotic. Moreover, overexpression of drug efflux pumps rendered to reduce uptake of the antibiotic inside the cell, by pumping out the antibiotics from the cell. In contrast, encapsulation of biofilm over the cell boundary reduces the cell permeability to resist antibiotics entry into the cell. The expression of chromosomal β-lactamase can be induced by either producing the plasmid-encoded penicillinase (β-lactamase) enzyme that hydrolyzes β-lactam ring or expression of PBP2a, and a penicillin-binding protein (PBP) encoded by gene *mecA* spread through horizontal gene transfer with low affinity to β-lactam antibiotics is primarily responsible for penicillin resistance [17]. The penicillin-binding cascade induces the blaZ-encoded penicillinase in *S. aureus*, which is transcriptionally regulated by regulatory genes blaI and blaR1 [26, 29].

**Figure 1.** β*-Lactam resistance mechanism of* S. aureus*.*
