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. 2017 Oct 24;61(11):e00932-17.
doi: 10.1128/AAC.00932-17. Print 2017 Nov.

PBP4 Mediates β-Lactam Resistance by Altered Function

Som S Chatterjee  1 , Liang Chen  2 , Aubre Gilbert  3 , Thaina M da Costa  3 , Vinod Nair  4 , Sandip K Datta  5 , Barry N Kreiswirth  2 , Henry F Chambers  3
Affiliations

PBP4 Mediates β-Lactam Resistance by Altered Function

Som S Chatterjee et al. Antimicrob Agents Chemother. .

Abstract

Penicillin binding protein 4 (PBP4) can provide high-level β-lactam resistance in Staphylococcus aureus A series of missense and promoter mutations associated with pbp4 were detected in strains that displayed high-level resistance. We show here that the missense mutations facilitate the β-lactam resistance mediated by PBP4 and the promoter mutations lead to overexpression of pbp4 Our results also suggest a cooperative interplay among PBPs for β-lactam resistance.

Keywords: PBP4; Staphylococcus aureus; β-lactam resistance.

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Figures

FIG 1
FIG 1
PBP4 missense mutations confer β-lactam resistance. pbp4 from wild-type (COLn) and mutant passaged strains were cloned in constitutively expressed vector pTXΔ. The resultant plasmids were transformed into the surrogate recipient COLnex Δpbp4 strain, and population analysis was carried out in nafcillin. Two-way analysis of variance of the data revealed a significant difference (P < 0.0417) between strains.
FIG 2
FIG 2
pbp4 promoter mutations cause enhanced pbp4 expression. pbp4 promoters from wild-type (COLn) and mutant passaged strains were cloned into lux reporter plasmid pAmilux. Lux signals and bacterial optical density at 600 nm (OD600) were measured at 4 h postculture, and data are represented by dividing the lux signal by OD600. P values of <0.0001 were revealed by nonparametric t test between wild-type and other strains.
FIG 3
FIG 3
Transmission electron microscopy reveals cell wall thickening of CRB.
See this image and copyright information in PMC

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