Staphylococcus aureus Strain Newman D2C Contains Mutations in Major Regulatory Pathways That Cripple Its Pathogenesis
is a major human pathogen that imposes a great burden on the health care system. In the development of antistaphylococcal modalities intended to reduce the burden of staphylococcal disease, it is imperative to select appropriate models of strains when assessing the efficacy of novel agents. Here, us...
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Published in | Journal of bacteriology Vol. 199; no. 24 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
15.12.2017
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Subjects | |
Online Access | Get full text |
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Summary: | is a major human pathogen that imposes a great burden on the health care system. In the development of antistaphylococcal modalities intended to reduce the burden of staphylococcal disease, it is imperative to select appropriate models of
strains when assessing the efficacy of novel agents. Here, using whole-genome sequencing, we reveal that the commonly used strain Newman D2C from the American Type Culture Collection (ATCC) contains mutations that render the strain essentially avirulent. Importantly, Newman D2C is often inaccurately referred to as simply "Newman" in many publications, leading investigators to believe it is the well-described pathogenic strain Newman. This study reveals that Newman D2C carries a stop mutation in the open reading frame of the virulence gene regulator,
In addition, Newman D2C carries a single-nucleotide polymorphism (SNP) in the global virulence regulator gene
that results in loss of protein function. This loss of function is highlighted by complementation studies, where the
allele from Newman D2C is incapable of restoring functionality to an
-null mutant. Additional functional assessment was achieved through the use of biochemical assays for protein secretion,
intoxications of human immune cells, and
infections. Altogether, our study highlights the importance of judiciously screening for genetic changes in model
strains when assessing pathogenesis or the efficacy of novel agents. Moreover, we have identified a novel SNP in the virulence regulator gene
that directly affects the ability of the protein product to activate
virulence pathways.
is a human pathogen that imposes an enormous burden on health care systems worldwide. This bacterium is capable of evoking a multitude of disease states that can range from self-limiting skin infections to life-threatening bacteremia. To combat these infections, numerous investigations are under way to develop therapeutics capable of thwarting the deadly effects of the bacterium. To generate successful treatments, it is of paramount importance that investigators use suitable models for examining the efficacy of the drugs under study. Here, we demonstrate that a strain of
commonly used for drug efficacy studies is severely mutated and displays markedly reduced pathogenicity. As such, the organism is an inappropriate model for disease studies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Citation Sause WE, Copin R, O'Malley A, Chan R, Morrow BJ, Buckley PT, Fernandez J, Lynch AS, Shopsin B, Torres VJ. 2017. Staphylococcus aureus strain Newman D2C contains mutations in major regulatory pathways that cripple its pathogenesis. J Bacteriol 199:e00476-17. https://doi.org/10.1128/JB.00476-17. R. Copin and A. O'Malley contributed equally to this work. |
ISSN: | 0021-9193 1098-5530 |
DOI: | 10.1128/JB.00476-17 |