Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion

Dan Xu, Chongbing Liao, Bing Zhang, W. David Tolbert, Wangxiao He, Zhijun Dai, Wei Zhang, Weirong Yuan, Marzena Pazgier, Jiankang Liu, Jun Yu, Philippe J. Sansonetti, Charles L. Bevins, Yongping Shao, Wuyuan Lu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human a-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.
LanguageEnglish
Pages1233-1244
Number of pages12
JournalImmunity
Volume48
Issue number6
Early online date29 May 2018
DOIs
Publication statusPublished - 19 Jun 2018

Fingerprint

Bacterial Adhesion
Defensins
Shigella
Infection
Intestinal Mucosa
Innate Immunity
Bacillary Dysentery
Bacterial Proteins
Virulence Factors
Gram-Negative Bacteria
Membrane Proteins
Mucous Membrane
Homeostasis
Animal Models
Pathology
Inflammation
Peptides

Keywords

  • a-Defensin 5
  • Shigella
  • adhesin
  • invasion
  • infection

Cite this

Xu, D., Liao, C., Zhang, B., Tolbert, W. D., He, W., Dai, Z., ... Lu, W. (2018). Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion. Immunity, 48(6), 1233-1244. https://doi.org/10.1016/j.immuni.2018.04.014
Xu, Dan ; Liao, Chongbing ; Zhang, Bing ; Tolbert, W. David ; He, Wangxiao ; Dai, Zhijun ; Zhang, Wei ; Yuan, Weirong ; Pazgier, Marzena ; Liu, Jiankang ; Yu, Jun ; Sansonetti, Philippe J. ; Bevins, Charles L. ; Shao, Yongping ; Lu, Wuyuan. / Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion. In: Immunity. 2018 ; Vol. 48, No. 6. pp. 1233-1244.
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abstract = "Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human a-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.",
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Xu, D, Liao, C, Zhang, B, Tolbert, WD, He, W, Dai, Z, Zhang, W, Yuan, W, Pazgier, M, Liu, J, Yu, J, Sansonetti, PJ, Bevins, CL, Shao, Y & Lu, W 2018, 'Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion' Immunity, vol. 48, no. 6, pp. 1233-1244. https://doi.org/10.1016/j.immuni.2018.04.014

Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion. / Xu, Dan; Liao, Chongbing; Zhang, Bing; Tolbert, W. David; He, Wangxiao; Dai, Zhijun; Zhang, Wei; Yuan, Weirong; Pazgier, Marzena; Liu, Jiankang; Yu, Jun; Sansonetti, Philippe J.; Bevins, Charles L.; Shao, Yongping; Lu, Wuyuan.

In: Immunity, Vol. 48, No. 6, 19.06.2018, p. 1233-1244.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human enteric a-defensin 5 promotes shigella infection by enhancing bacterial adhesion and invasion

AU - Xu, Dan

AU - Liao, Chongbing

AU - Zhang, Bing

AU - Tolbert, W. David

AU - He, Wangxiao

AU - Dai, Zhijun

AU - Zhang, Wei

AU - Yuan, Weirong

AU - Pazgier, Marzena

AU - Liu, Jiankang

AU - Yu, Jun

AU - Sansonetti, Philippe J.

AU - Bevins, Charles L.

AU - Shao, Yongping

AU - Lu, Wuyuan

PY - 2018/6/19

Y1 - 2018/6/19

N2 - Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human a-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.

AB - Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella coopts human a-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.

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KW - Shigella

KW - adhesin

KW - invasion

KW - infection

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DO - 10.1016/j.immuni.2018.04.014

M3 - Article

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T2 - Immunity

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SN - 1074-7613

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ER -