Mutagenesis of the Shigella Flexneri Autotransporter IcsA Reveals Novel Functional Regions Involved in IcsA Biogenesis and Recruitment of Host Neural Wiscott-Aldrich Syndrome Protein

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 2008 May 6

PMID 18456802

Citations 23

Authors

Kerrie L May

Renato Morona

Affiliations

Soon will be listed here.

Abstract

The IcsA (VirG) protein of Shigella flexneri is a polarly localized, outer membrane protein that is essential for virulence. Within host cells, IcsA activates the host actin regulatory protein, neural Wiskott-Aldrich syndrome protein (N-WASP), which in turn recruits the Arp2/3 complex, which nucleates host actin to form F-actin comet tails and initiate bacterial motility. Linker insertion mutagenesis was undertaken to randomly introduce 5-amino-acid in-frame insertions within IcsA. Forty-seven linker insertion mutants were isolated and expressed in S. flexneri Delta icsA strains. Mutants were characterized for IcsA protein production, cell surface expression and localization, intercellular spreading, F-actin comet tail formation, and N-WASP recruitment. Using this approach, we have identified a putative autochaperone region required for IcsA biogenesis, and our data suggest an additional region, not previously identified, is required for N-WASP recruitment.

Citing Articles

Cysteine-Dependent Conformational Heterogeneity of Shigella flexneri Autotransporter IcsA and Implications of Its Function.

Qin J, Hong Y, Morona R, Totsika M Microbiol Spectr. 2022; 10(6):e0341022.

PMID: 36374106 PMC: 9769942. DOI: 10.1128/spectrum.03410-22.

The virulence domain of Shigella IcsA contains a subregion with specific host cell adhesion function.

Qin J, Doyle M, Tran E, Morona R PLoS One. 2020; 15(1):e0227425.

PMID: 31910229 PMC: 6946128. DOI: 10.1371/journal.pone.0227425.

Evolutionary Perspectives on the Moonlighting Functions of Bacterial Factors That Support Actin-Based Motility.

Koseoglu V, Agaisse H mBio. 2019; 10(4).

PMID: 31455648 PMC: 6712393. DOI: 10.1128/mBio.01520-19.

Establishment of a Protein Concentration Gradient in the Outer Membrane Requires Two Diffusion-Limiting Mechanisms.

Ginez L, Osorio A, Camarena L, Poggio S J Bacteriol. 2019; 201(17).

PMID: 31209077 PMC: 6689296. DOI: 10.1128/JB.00177-19.

Identification of the Autochaperone Domain in the Type Va Secretion System (T5aSS): Prevalent Feature of Autotransporters with a β-Helical Passenger.

Rojas-Lopez M, Zorgani M, Kelley L, Bailly X, Kajava A, Henderson I Front Microbiol. 2018; 8:2607.

PMID: 29375499 PMC: 5767081. DOI: 10.3389/fmicb.2017.02607.

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