Mahtab Azizi,1,*
1. Islamic Azad University North Tehran Branch
Introduction: Antibiotics are used to treat a number of infections caused by Staphylococcus aureus. The key bacterial processes that are targeted by a number of antibiotics used to treat staphylococcal infections include cell wall formation, translation, transcription, and DNA synthesis. Antibiotic resistance, however, is an issue that is getting worse, and unsuccessful treatments have high costs in terms of both money and lives. A large number of mobile genetic elements contribute to the spread of antibiotic resistance. These elements include altered drug targets, enzymatic drug inactivation, enhanced efflux of antimicrobial chemicals, and altered drug accessibility. Although almost all compounds have shown resistance, specific strains resistant to all medications have not yet been identified. Yet resistance still poses treatment challenges, as exemplified by vancomycin. The aim of this study was to investigate Antibiotic Resistance and the MRSA Problem.
Methods: With the title "Antibiotic Resistance and the MRSA Problem," this review study has been created using information from scholarly databases like Science Direct, Springer, Google Scholar, and PubMed.
Results: A notable feature of most MRSA isolates is that resistance to beta-lactams is expressed in a heterogeneous manner. For these strains, populations arising from a single cell display widely different resistance levels, with the majority of cells exhibiting a low level of resistance and a minority of cells being highly resistant. While some HA-MRSA isolates exhibit high-level, homogeneous methicillin resistance, CA-MRSA isolates often exhibit low-level, heterogeneous resistance. Insight into the molecular mechanisms underlying this phenomenon has come from the identification of mutations that convert strains expressing low, heterogeneous resistance into homogeneous, highly resistant strains. These mutations map to genes associated with cellular stress responses, such as stringent response signaling via ppGpp and the ClpXP protease controlling the Spx stress response indicating a close link between bacterial physiology and resistance levels. Despite the fact that MRSA strains have become resistant to beta-lactams through acquisition of one specific resistance determinant, the mecA gene, clinical MRSA isolates exhibit highly variable levels of resistance: in some MRSA strains resistance is barely above that displayed by susceptible isolates (methicillin MICs <3 μg/ml), while other strains are highly resistant (methicillin MICs up to 1,600 μg/ml). The mechanisms underlying these intriguing differences in resistance level remain poorly understood. In some cases, high resistance levels were attributed to increased expression of PBP2a due to duplication or enhanced transcription of the mecA gene. Two functionally similar two-component systems, BlaR1/BlaI and MecR1/MecI, control transcription of mecA in response to beta-lactams, and because genetic mutations are common in the regulatory elements controlling mecA expression, the PBP2a level varies widely between MRSA strains. In several cases differences in resistance levels did not correlate to PBP2a expression, suggesting that factors other than PBP2a modulate the strain-specific level of beta-lactam resistance. Indeed, genetic screens have identified a number of auxiliary factors (also designated “fem- factors”) essential for methicillin resistance that are critical for PBP2a-mediated resistance to beta-lactam antibiotics. Examples include cell division proteins, native PBPs, and enzymes involved in the synthesis of teichoic acids and peptidoglycan precursors. In some cases, the requirements for these auxiliary factors have been explained. For example, the essential glycosyltransferase domain of the native PBP2 is needed to cooperate with the transpeptidase activity of PBP2a in the building of peptidoglycan.
Conclusion: Since medications that block the actions of auxiliary factors operate in conjunction with beta-lactams to kill MRSA, the fact that beta lactam resistance depends on them offers up new therapeutic options for MRSA infections.