Recent headlines have highlighted the spread of MRSA infectionin the United States. Accoridng to the CDC, MRSA is responsible forover 90,000 serious infections and over 18,000 hospitalstay-related deaths per year in the United States. These MRSAstrains are responsible for many serious skin and soft tissueinfections, as well as pneumonia. One major problem with MRSA isthat occasionally the skin infection can spread to other organs ofthe body with more severe, life threatening symptoms, includingnecrotizing fasciitis and necrotizing pneumonia, followed by sepsisand toxic shock, and then death in up to 50% of cases. A strikingfinding about these infections is that they occur in youngimmunocompetent patients who were previously healthy. MRSA isresistant to several commonly prescribed antibiotics that areusually effective against gram-positive bacteria (methicillin,penicillin, and cephalosporins), and an infection with MRSA straincan be deadly if left untreated. MRSA is subcategorized ascommunity aquired or hospital aquired, depending on how theinfection is usually aquired. Most community aquired MRSA strainsare still sensitive to many antibiotics, such as trimethoprim,tetracycline, and clindamycin, but hospital aquired MRSA strainsare often resistant to these drugs will still sensitive tovancomycin and linezolid.

A) Provide common mechanism that accounts for the observedresistance of MRSA to methicillin, penicillin, and cephalosporin.Provide two different strategies that could be used to overcomethis particular resistance.

B) For each of the antibiotics trimethoprim, tetracycline, andclindamycin, provide a possible mechanism to account for theobserved resistance of HA-MrSA to the antibiotic. Provide astrategy that could be used to treat patients infected with HA-MRSAresistant to these antibiotics.

C) Why would HA-MRSA strains that are resistant to methicillin,penicillin, cephalosporins, trimethoprim, tetraculine andclindamysic still show sensitivity to vancomycin and linezolid?

D) Although CA-MRSA is resistant to clindamycin, treatment withclindamycin in combination with rifampin results in an increase inthe 50% lethal dose (LD50) value from 10 without antibiotictreatment to 10^4 with rifampin to 10^8 for combined treatment withclindamycin and rifampin. In addtion, treatment with clindamycinenhanced opsonization of CA-MRSA by macrophages. What possiblemechanism(s) could account for these observations (i.e., change inthe LD50 value and enhanced opsonization)? Provide your rationale.Provide an experiment that could be performed to confirm yourhypothesis.