Abstract：
:The use of β-lactam antibiotics to treat infections caused by Staphylococcus aureus has been severely compromised by the acquisition by horizontal gene transfer of a gene that encodes the β-lactam-insensitive penicillin-binding protein PBP2a. This allows methicillin-resistant S. aureus (MRSA) to proliferate in the presence of β-lactam antibiotics. Paradoxically the dependence on PBP2a for the essential transpeptidase activity in cell wall peptidoglycan biosynthesis is the 'Achilles heel' of MRSA. Compounds that disrupt the divisome, wall teichoic acid, and functional membrane microdomains act synergistically with β-lactams against MRSA. These include drugs such as statins that are widely used in human medicine. The antibiotics vancomycin and daptomycin are also synergistic with β-lactams, and combinations have been employed to treat persistent MRSA infections. An additional benefit of exposing MRSA to β-lactams could be a reduction in virulence mediated by interfering with the global regulator Agr. The mechanistic basis of synergy is discussed, and the possibility that β-lactams can be resurrected to combat MRSA infections is explored.
journal_name
Trends Microbioljournal_title
Trends in microbiologyauthors
Foster TJdoi
10.1016/j.tim.2018.06.005subject
Has Abstractpub_date
2019-01-01 00:00:00pages
26-38issue
1eissn
0966-842Xissn
1878-4380pii
S0966-842X(18)30140-9journal_volume
27pub_type
杂志文章,评审abstract：:Progress in understanding the evolution of infectious diseases has inspired proposals to manage the evolution of pathogen (including parasite) virulence. A common view is that social interventions that lower pathogen transmission will indirectly select lower virulence because of a trade-off between transmission and vi...
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journal_title：Trends in microbiology
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journal_title：Trends in microbiology
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journal_title：Trends in microbiology
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journal_title：Trends in microbiology
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journal_title：Trends in microbiology
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