Brucella Periplasmic Protein EipB Is a Molecular Determinant of Cell Envelope Integrity and Virulence

Herrou, Julien; Willett, Jonathan W.; Fiebig, Aretha; Czyż, Daniel M.; Cheng, Jason X.; Ultee, Eveline; Briegel, Ariane; Bigelow, Lance; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean

doi:10.1128/JB.00134-19

Title: Brucella Periplasmic Protein EipB Is a Molecular Determinant of Cell Envelope Integrity and Virulence

Journal Article · Mon Apr 01 00:00:00 EDT 2019 · Journal of Bacteriology

DOI:https://doi.org/10.1128/JB.00134-19· OSTI ID:1573254

Herrou, Julien ^[1]; Willett, Jonathan W. ^[1];

^[1]; Czyż, Daniel M. ^[2]; Cheng, Jason X. ^[1]; Ultee, Eveline ^[3]; Briegel, Ariane ^[3]; Bigelow, Lance ^[4]; Babnigg, Gyorgy ^[4]; Kim, Youngchang ^[4];

^[1]

Univ. of Chicago, IL (United States)
Univ. of Florida, Gainesville, FL (United States)
Univ. Leiden (Netherlands)
Argonne National Lab. (ANL), Argonne, IL (United States)

The Gram-negative cell envelope is a remarkable structure with core components that include an inner membrane, an outer membrane, and a peptidoglycan layer in the periplasmic space between. Multiple molecular systems function to maintain integrity of this essential barrier between the interior of the cell and its surrounding environment. Herein, we show that a conserved DUF1849 family protein, EipB, is secreted to the periplasmic space of Brucella species, a monophyletic group of intracellular pathogens. In the periplasm, EipB folds into an unusual 14-stranded β-spiral structure that resembles the LolA and LolB lipoprotein delivery system, though the overall fold of EipB is distinct from LolA/LolB. Deletion of eipB results in defects in Brucella cell envelope integrity in vitro and in maintenance of spleen colonization in a mouse model of Brucella abortus infection. Transposon disruption of ttpA, which encodes a periplasmic protein containing tetratricopeptide repeats, is synthetically lethal with eipB deletion. ttpA is a reported virulence determinant in Brucella, and our studies of ttpA deletion and overexpression strains provide evidence that this gene also contributes to cell envelope function. We conclude that eipB and ttpA function in the Brucella periplasmic space to maintain cell envelope integrity, which facilitates survival in a mammalian host.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID)

Grant/Contract Number:: AC02-06CH11357; U19AI107792; R01AI107159

OSTI ID:: 1573254

Journal Information:: Journal of Bacteriology, Vol. 201, Issue 12; ISSN 0021-9193

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 8 works

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Title: Brucella Periplasmic Protein EipB Is a Molecular Determinant of Cell Envelope Integrity and Virulence

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