Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Nov;54(11):4900-2.
doi: 10.1128/AAC.00594-10. Epub 2010 Aug 30.

A mecA-negative strain of methicillin-resistant Staphylococcus aureus with high-level β-lactam resistance contains mutations in three genes

Affiliations

A mecA-negative strain of methicillin-resistant Staphylococcus aureus with high-level β-lactam resistance contains mutations in three genes

Ritu Banerjee et al. Antimicrob Agents Chemother. 2010 Nov.

Abstract

We previously generated a ceftobiprole-resistant Staphylococcus aureus strain after high inoculum serial passage of a mecA-negative variant of strain COL (R. Banerjee, M. Gretes, L. Basuino, N. Strynadka, and H. F. Chambers, Antimicrob. Agents Chemother. 52:2089-2096, 2008). Genome resequencing of this strain, CRB, revealed that it differs from its parent by five single-nucleotide polymorphisms in three genes, specifically, those encoding PBP4, a low-molecular-weight penicillin-binding protein, GdpP, a predicted signaling protein, and AcrB, a cation multidrug efflux transporter. CRB displayed resistance to a variety of β-lactams but was hypersusceptible to cefoxitin.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
PBP4 crystal structure (gray ribbon) in complex with cefotaxime (purple) as recently reported (21), shows that residues F241 and E183 (blue; mutated in ceftobiprole-resistant strain CRB) are adjacent to the active site. Active-site residues S75, S139, and K259 are shown in green. Noncarbon atoms are colored according to the CPK convention.

References

    1. Banerjee, R., M. Gretes, L. Basuino, N. Strynadka, and H. F. Chambers. 2008. In vitro selection and characterization of ceftobiprole-resistant methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 52:2089-2096. - PMC - PubMed
    1. Boucher, H. W., G. H. Talbot, J. S. Bradley, J. J. E. Edwards, D. Gilbert, L. B. Rice, M. Scheld, B. Spellberg, and J. Bartlett. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1-12. - PubMed
    1. Chambers, H. F., M. J. Sachdeva, and C. J. Hackbarth. 1994. Kinetics of penicillin binding to penicillin-binding proteins of Staphylococcus aureus. Biochem. J. 301:139-144. - PMC - PubMed
    1. Chen, Y.-J., J. Sims-Mourtada, J. Izzo, and K. S. C. Chao. 2007. Targeting the hedgehog pathway to mitigate treatment resistance. Cell Cycle 15:1826-1830. - PubMed
    1. Davies, T. A., M. G. P. Page, W. Shang, T. Andrew, M. Kania, and K. Bush. 2007. Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51:2621-2624. - PMC - PubMed

Publication types

MeSH terms