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The GAS PefCD exporter is a MDR system that confers resistance to heme and structurally diverse compounds

Overview of attention for article published in BMC Microbiology, April 2016
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Title
The GAS PefCD exporter is a MDR system that confers resistance to heme and structurally diverse compounds
Published in
BMC Microbiology, April 2016
DOI 10.1186/s12866-016-0687-6
Pubmed ID
Authors

Ankita J. Sachla, Zehava Eichenbaum

Abstract

Group A streptococcus (GAS) is the etiological agent of a variety of local and invasive infections as well as post-infection complications in humans. This β-hemolytic bacterium encounters environmental heme in vivo in a concentration that depends on the infection type and stage. While heme is a noxious molecule, the regulation of cellular heme levels and toxicity is underappreciated in GAS. We previously reported that heme induces three GAS genes that are similar to the pefRCD (porphyrin regulated efflux) genes from group B streptococcus. Here, we investigate the contributions of the GAS pef genes to heme management and physiology. In silico analysis revealed that the PefCD proteins entail a Class-1 ABC-type transporter with homology to selected MDR systems from Gram-positive bacteria. RT-PCR experiments confirmed that the pefRCD genes are transcribed to polycistronic mRNA and that a pefC insertion inactivation mutant lost the expression of both pefC and pefD genes. This mutant was hypersensitive to heme, exhibiting significant growth inhibition already in the presence of 1 μM heme. In addition, the pefC mutant was more sensitive to several drugs and nucleic acid dyes and demonstrated higher cellular accumulation of heme in comparison with the wild type and the complemented strains. Finally, the absence of the PefCD transporter potentiated the damaging effects of heme on GAS building blocks including lipids and DNA. We show here that in GAS, the pefCD genes encode a multi-drug efflux system that allows the bacterium to circumvent the challenges imposed by labile heme. This is the first heme resistance machinery described in GAS.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 27%
Professor > Associate Professor 3 27%
Student > Ph. D. Student 2 18%
Professor 1 9%
Unknown 2 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 55%
Agricultural and Biological Sciences 2 18%
Veterinary Science and Veterinary Medicine 1 9%
Unknown 2 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 April 2016.
All research outputs
#6,562,086
of 7,578,098 outputs
Outputs from BMC Microbiology
#1,041
of 1,280 outputs
Outputs of similar age
#224,155
of 267,247 outputs
Outputs of similar age from BMC Microbiology
#56
of 68 outputs
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