**3. β-Lactam resistance in** *S. aureus*

According to the European Centre for Diseases Control (ECDC), antimicrobial resistance is the single biggest threat facing the world in the area of infectious diseases. With the progression of antibiotics discoveries and their prophylactic usages have emerged drug resistance to single or multiple drugs. Antibiotic resistance is a natural selection process when microorganisms are treated with different antibiotics, and microorganisms tend to escape this selection pressure with greater competency to survive and thus show antibiotics resistance. In contrast, bacteria with a susceptible nature are killed with exposed antibiotics. Emerging resistance to β-LA is a serious health concern that causes a major hurdle in the treatment of bacterial infections. The condition of drug resistance is primarily developed by increasing and indiscriminate usage of antibiotics in clinical ailments, unregulated sales of antibiotics, a long course of medication, and poor public health infrastructure. According to a hospital survey, over 80% of clinical samples of *S. aureus* were established resistance to the frontline antibiotics including methicillin [24, 25]. It has been reported that 70% of nosocomial bacterial pathogens have emerged resistance to more than one antibiotic during medication of chronic infections. In contrast, an alarming increase in resistance of community-acquired bacteria has also been observed with significant high rate both in acute and chronic bacterial infections. The emergence of drug-resistant strains of Gram-positive (*Staphylococcus, Enterococcus, Streptococcus sp*) and Gram-negative (*Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Salmonella sp*) bacteria is the more serious in the present therapeutic scenario. *S. aureus* clearly represents one of the most challenging pathogenic bacteria. Resistance in *S. aureus* strains has been continuously increasing; thus, the ability of these pathogens to spread in both hospital and community settings increased. Bacteria remarkably developed resistant to antimicrobial drugs in several ways. Upon antibiotics treatment, bacteria tend to overcome the selection pressure of the drug by morphological and genetic alterations or drug inactivation. Alterations of membrane integrity and transfer of resistance genes from one strain to another are the common examples of β-LA-mediated resistance in *S. aureus.* β-LA, Penicillin was initially succeeded in the treatment of *S. aureus* infections but widespread and prolonged uses of penicillin were no longer be effective and resistance has been emerged soon after in the 1950s [19]. Antibiotic resistance can be a typical feature of a bacterial species (intrinsic resistance) or acquired by the individual organism that is naturally susceptible (acquired resistance). The acquired resistance is the consequence of chromosomal mutations or acquisition of resistance genes by horizontal gene transfer [26]. Resistance to multiple β-LA can be acquired by individual strains, resulting in multidrug-resistant phenotypes. The high prevalence of drug resistance is primarily adopted by unregulated sales of antibiotics without prescription, a long course of medication, indiscriminate usage of drugs, and poor health infrastructure. The mobility and mortality caused by drug resistance in public

health are difficult to evaluate. In 2013, Center for Disease Control and Prevention (CDC) reported more than 11,000 deaths in the USA had a methicillin-resistant *S. aureus* (MRSA)-related infection (CDC 2013). This represents almost 50% of all causalities caused by antibiotic-resistant bacteria. As per WHO report, the MRSA remains among the high-priority multidrug-resistant organisms that need renewed efforts for the research and development of new antibiotics and innovative preventive approaches.
