title: PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus.
abstract: Staphylococcus aureus is an important cause of both hospital- and community-associated methicillin-resistant S. aureus (MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treat S. aureus infections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance of S. aureus has always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by the mecA gene. Here, we show that S. aureus can also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams.
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: Liana C
authors.initials: LC
authors.lastname: Chan
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: Aubre
authors.initials: A
authors.lastname: Gilbert
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Basuino
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thaina M
authors.initials: TM
authors.lastname: da Costa
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Hamilton
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Katia R
authors.initials: KR
authors.lastname: Dos Santos
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
authors.affiliation: Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, California, USA som.chatterjee@ucsf.edu.
authors.forename: Som S
authors.initials: SS
authors.lastname: Chatterjee
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002511:Cephalosporins / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018440:beta-Lactam Resistance / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams