Comparative structural analysis of MecA encoded beta-lactam resistance in MRSA

Abstract

As the level of antibiotic resistance in bacteria rises, the threat of patients facing fatal consequences from a simple cut or infection grows dramatically. One example of an emerging antibiotic-resistant threat is MRSA, methicillin-resistant staphylococcus aureus, which is a growing cause of hospital-acquired pneumonia, skin infections, and even sepsis through cross-contamination in health care settings. Therefore it is advantageous to investigate the evolution of methicillin resistance in Staphylococcus aureus to predict trends in what factors contribute to the transfer and evolution of resistance in superbugs like MRSA. However, methicillin resistance like that exploited by MRSA is also highly conserved with that of another species of staphylococcus bacteria, Staphylococcus sciuri which is the ancestral bacterium of S. aureus. S. sciuri is a typically animal-associated bacterium with increasing clinical relevance as the amount of human infections from it has grown. Both these bacteria share the commonality of having the mecA gene that determines methicillin resistance transported through the mobile Staphylococcal cassette chromosome. This study focuses on the relationship between the mecA mobile element in S. sciuri compared to S. aureus and explores the specific role of S. sciuri in the creation of the mecA cassette. Understanding the cassette evolution and similarities and differences between S. sciuri and S. aureus will enable the continued tracking of S. sciuri as an emerging clinical threat. To answer all these questions, BLAST analysis, InterProScan, and additional computational analysis were used to characterize differences in homology, structure, function, and effect on infectivity, robustness of antibiotic resistance, and morbidity. The overall goal of this analysis is to characterize the differences between mecA and methicillin-resistant genes in clinically relevant MRSA as well as environmental samples such as S. sciuri to understand their growth.