Ail Protein Binds Ninth Type III Fibronectin Repeat (9FNIII) within Central 120-kDa Region of Fibronectin to Facilitate Cell Binding by Yersinia pestis

Tsang, Tiffany; Annis, Douglas S.; Kronshage, Malte; Fenno, Jesse T.; Usselman, Lisa D.; Mosher, Deane F.; Krukonis, Eric S.

doi:10.1074/jbc.m112.358978

Cited by 31 publications

(31 citation statements)

References 64 publications

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“…The protein termed "attachment and invasion locus" (Ail) belongs to the family of outer membrane proteins, and promotes cell attachment and invasion. Ail is furthermore required for full virulence of Y. pestis and the delivery of pathogenicity factors into host cells (9)(10)(11)(12). The invasin subfamily comprises adhesins of the inverse autotransporter group also referred to as type Ve secretion system (13,14).…”

mentioning

confidence: 99%

The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

Sadana

Geyer

Pezoldt

et al. 2018

Journal of Biological Chemistry

601

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mentioning

confidence: 99%

The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

Sadana

Geyer

Pezoldt

et al. 2018

Journal of Biological Chemistry

601

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“…On the other hand, MsbB modifies lipopolysaccharide (LPS) by adding lauric acid to the lipid A moiety, resulting in the increased biological potency of LPS (22)(23)(24)(25)(26)(27). Ail is an ϳ17-kDa outer membrane protein with four extracellular loops, and loop 2 (L2) has been reported to be mainly responsible for Ail-mediated bacterial serum resistance and adherence to/invasion of the host cells (17,(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

mentioning

confidence: 99%

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Tiner

Sha

Ponnusamy

et al. 2015

Clin. Vaccine Immunol.

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Y ersinia pestis is the causative agent of plague (1), and there has been a rise in the number of plague cases globally in recent years possibly due to climate changes and shifting of the rodent carrier range (2). The organism is classified as a tier 1 select agent (3-5), and the progression of septicemic and pneumonic forms of plague is very rapidly fatal after the first appearance of symptoms (4, 6-8). Alarmingly, antibiotic-resistant strains of Y. pestis have been isolated from plague patients and also have been engineered for bioweaponization (4). Therefore, vaccination is the optimal strategy for human protection against this deadly disease; however, there are currently no Food and Drug Administration (FDA)-licensed plague vaccines available in the United States (9-11).Although a heat-killed plague vaccine composed of the Y. pestis 195/P strain was in use in the United States until 1999, the production of this vaccine was discontinued because of its effectiveness only against the bubonic plague and not the pneumonic form and also because it was highly reactogenic in humans (12, 13). Various live-attenuated Y. pestis EV76 vaccine strains, which lack the pigmentation locus (pgm) required for iron acquisition, provide protection against bubonic and pneumonic plague and are being used in some parts of the world where plague is endemic (9). However, these EV76-based vaccines are not genetically uniform and are also highly reactogenic (14); hence, they do not meet the standards for FDA approval. In addition, the ⌬pgm mutants of Y. pestis (e.g., the KIM/D27 strain) may not be safe because of a reported case of fatal infection in an individual with hemochromatosis (15,16).In an effort to search for a new live-attenuated plague vaccine, we recently constructed a ⌬lpp ⌬msbB ⌬ail triple mutant, with deleted genes encoding Braun lipoprotein (Lpp), an acetyltransferase (MsbB), and the attachment invasion locus (Ail) (17). Lpp

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“…By binding the central region of Fn, Ail can facilitate cell adhesion and Yop delivery to host cells (13,15). Thus, we tested the various Ail mutant proteins for the ability to bind Fn immobilized on 96-well plates.…”

Section: Resultsmentioning

confidence: 99%

Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery

et al. 2017

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Yersinia pestis, the causative agent of plague, binds host cells to deliver cytotoxic Yop proteins into the cytoplasm that prevent phagocytosis and generation of proinflammatory cytokines. Ail is an eight-stranded β-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. Following the deletion of each of the four extracellular loops that potentially interact with host cells, the Ail-Δloop 2 and Ail-Δloop 3 mutant proteins had no cell-binding activity while Ail-Δloop 4 maintained cell binding (the Ail-Δloop 1 protein was unstable). Using the codon mutagenesis scheme SWIM (selection without isolation of mutants), we identified individual residues in loops 1, 2, and 3 that contribute to host cell binding. While several residues contributed to the binding of host cells and purified fibronectin and laminin, as well as Yop delivery, three mutations, F80A (loop 2), S128A (loop 3), and F130A (loop 3), produced particularly severe defects in cell binding. Combining these mutations led to an even greater reduction in cell binding and severely impaired Yop delivery with only a slight defect in serum resistance. These findings demonstrate that Y. pestis Ail uses multiple extracellular loops to interact with substrates important for adhesion via polyvalent hydrophobic interactions.

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Ail Protein Binds Ninth Type III Fibronectin Repeat (9FNIII) within Central 120-kDa Region of Fibronectin to Facilitate Cell Binding by Yersinia pestis

Cited by 31 publications

References 64 publications

The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery

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