-Lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli

Hirakawa, Hidetada; Nishino, Kunihiko; Yamada, Jun; Hirata, Takahiro; Yamaguchi, Akihito

doi:10.1093/jac/dkg406

Cited by 116 publications

(82 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As is well known, AcrAB is responsible for the major part of efflux of β-lactams in E. coli (17,20). Although AcrD can make a significant contribution to β-lactam efflux when overexpressed, it is expressed at a very low level in uninduced cells (21).…”

Section: Resultsmentioning

confidence: 99%

Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels

Kojima

Nikaido

2013

Proc. Natl. Acad. Sci. U.S.A.

135

154

View full text Add to dashboard Cite

Small, hydrophilic compounds such as β-lactams diffuse across the outer membrane of Gram-negative bacteria through porin channels, which were originally thought to be nonspecific channels devoid of any specificity. However, since the discovery of an ampicillin-binding site within the OmpF channel in 2002, much attention has been focused on the potential specificity of the channel, where the binding site was assumed either to facilitate or to retard the penetration of β-lactams. Since the earlier studies on porin permeability were done without the knowledge of the contribution of multidrug efflux pumps in the overall flux process across the cell envelope, in this study we have carefully studied both the porin permeability and active efflux of ampicillin and benzylpenicillin. We found that the influx occurs apparently by a spontaneous passive diffusion without any indication of specific binding within the concentration range relevant to the antibiotic action of these drugs, and that the higher permeability for ampicillin is totally as expected from the gross property of this drug as a zwitterionic compound. The active efflux by AcrAB was more effective for benzylpenicillin due to the stronger affinity and high degree of positive cooperativity. Our data now give a complete quantitative picture of the influx, efflux, and periplasmic degradation (catalyzed by AmpC β-lactamase) of these two compounds, and correlate closely with the susceptibility of Escherichia coli strains used here, thus validating not only our model but also the parameters obtained in this study.AcrB | OmpC

show abstract

Section: Resultsmentioning

confidence: 99%

Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels

Kojima

Nikaido

2013

Proc. Natl. Acad. Sci. U.S.A.

135

154

View full text Add to dashboard Cite

show abstract

“…(29)(30)(31). A role for mdtABC in resistance to novobiocin, bile salts, deoxycholate, and β-lactam antibiotics has been demonstrated, and a role in transport of flavenoids and sodium tungstate has been suggested (29)(30)(31)(32)(33). MdtD is a predicted cytoplasmic membrane protein with 12-14 transmembrane domains.…”

Section: Resultsmentioning

confidence: 99%

Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance inSalmonellaTyphimurium

Frawley¹,

Crouch²,

Bingham-Ramos³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The efficacy of antibiotics and host defenses has been linked to the metabolic and redox states of bacteria. In this study we report that a stress-induced export pump belonging to the major facilitator superfamily effluxes citrate and iron from the enteric pathogen Salmonella Typhimurium to arrest growth and ameliorate the effects of antibiotics, hydrogen peroxide, and nitric oxide. The transporter, formerly known as MdtD, is now designated IceT (iron citrate efflux transporter). Iron efflux via an iron-chelating tricarboxylic acid cycle intermediate provides a direct link between aerobic metabolism and bacterial stress responses, representing a unique mechanism of resistance to host defenses and antimicrobial agents of diverse classes.

show abstract

“…The fnr gene was amplified with the primer pair shown in Table 2. The product was digested with NcoI and BamHI and ligated into the similarly digested pTrc99K plasmid (27) to generate pTrc99-6Hisfnr. The pTrc99-6HisfnrD154A plasmid was constructed by site-directed mutagenesis of pTrc99-6Hisfnr.…”

Section: Methodsmentioning

confidence: 99%

Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

Kurabayashi

Tanimoto

Fueki

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Because a shortage of new antimicrobial agents is a critical issue at present, and with the spread of multidrug-resistant (MDR) pathogens, the use of fosfomycin to treat infections is being revisited as a "last-resort option." This drug offers a particular benefit in that it is more effective against bacteria growing under oxygen-limited conditions, unlike other commonly used antimicrobials, such as fluoroquinolones and aminoglycosides. In this study, we showed that Escherichia coli strains, including enterohemorrhagic E. coli (EHEC), were more susceptible to fosfomycin when grown anaerobically than when grown aerobically, and we investigated how the activity of this drug was enhanced during anaerobic growth of E. coli. Our quantitative PCR analysis and a transport assay showed that E. coli cells grown under anaerobic conditions had higher levels of expression of glpT and uhpT, encoding proteins that transport fosfomycin into cells with their native substrates, i.e., glycerol-3-phosphate and glucose-6-phosphate, and led to increased intracellular accumulation of the drug. Elevation of expression of these genes during anaerobic growth requires FNR, a global transcriptional regulator that is activated under anaerobic conditions. Purified FNR bound to DNA fragments from regions upstream of glpT and uhpT, suggesting that it is an activator of expression of glpT and uhpT during anaerobic growth. We concluded that the increased antibacterial activity of fosfomycin toward E. coli under anaerobic conditions can be attributed to elevated expression of GlpT and UhpT following activation of FNR, leading to increased uptake of the drug.

show abstract

-Lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli

Abstract: Two-component signal transduction systems contribute to beta-lactam resistance in E. coli. Multidrug exporters play roles in two-component signal transduction system-mediated beta-lactam resistance.

Cited by 116 publications

References 23 publications

Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels

Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels

Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance inSalmonellaTyphimurium

Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

Contact Info

Product

Resources

About