Yersinia pestis Ail: multiple roles of a single protein

Abstract

Yersinia pestis is one of the most virulent bacteria identified. It is the causative agent of plague-a systemic disease that has claimed millions of human lives throughout history. Y. pestis survival in insect and mammalian host species requires fine-tuning to sense and respond to varying environmental cues. Multiple Y. pestis attributes participate in this process and contribute to its pathogenicity and highly efficient transmission between hosts. These include factors inherited from its enteric predecessors; Y. enterocolitica and Y. pseudotuberculosis, as well as phenotypes acquired or lost during Y. pestis speciation. Representatives of a large Enterobacteriaceae Ail/OmpX/PagC/Lom family of outer membrane proteins (OMPs) are found in the genomes of all pathogenic Yersiniae. This review describes the current knowledge regarding the role of Ail in Y. pestis pathogenesis and virulence. The pronounced role of Ail in the following areas are discussed (1) inhibition of the bactericidal properties of complement, (2) attachment and Yersinia outer proteins (Yop) delivery to host tissue, (3) prevention of PMNL recruitment to the lymph nodes, and (4) inhibition of the inflammatory response. Finally, Ail homologs in Y. enterocolitica and Y. pseudotuberculosis are compared to illustrate differences that may have contributed to the drastic bacterial lifestyle change that shifted Y. pestis from an enteric to a vector-born systemic pathogen.

Keywords: Ail; OmpX; T3SS; Yersinia pestis; adhesion; invasion; serum resistance; virulence.

Figure 1

Multiple strain sequence alignment and amino acid analysis of Ail. Gray letters indicate the signal sequence and the arrow indicates the signal sequence cleavage site (Kolodziejek et al., 2007). EL1, EL2, EL3, and EL4 designate extracellular loops; dotted line boxes indicate extracellular regions, including just the residues connecting two β strands (solid line boxes), as predicted from the crystal structure by Yamashita et al. (2011). Amino acid variation in the Ail polypeptide among Y. pestis strains is indicated by the presence of Val in the position 126 (Y. pestis Pestoides F, Angola, Y. pestis subsp. caucasica, altaica, hissarica) instead of Phe and additional substitution of Ser in the position 137 (Y. pestis Pestoides F, Y. pestis subsp. caucasica) (Eroshenko et al., 2010). Alignments of Ail from Y. pestis (y1324) with Ail from Y. pseudotuberculosis IP 32953, Y. enterocolitica 8081c, and three other Y. pestis Ail homologs (y1682, y2446, and y2034) are depicted. Indicated colors represent identical, strongly, and weakly similar residues. Alignments were produced with ClustalW.

Figure 2

Crystal structure of Ail. Extracellular loops are indicated EL1, EL2, EL3, and EL4 and the hydrophobic belt is indicated in color. The tips of EL2 and EL3 are disordered and these regions are marked with dotted lines (Yamashita et al., 2011). The figure was generated from the PDBe Protein Data Bank in Europe.

Figure 3

Correlation of E. coli and Y. pestis LPS structures and Ail-mediated phenotypes—schematic representation (Kolodziejek et al., 2010). (A) Key to LPS moieties. (B) LPS core structure of Y. pestis KM260 grown at ambient temperature; arrows indicate truncation of the core residues that resulted in loss of serum resistance (Knirel et al., ; Dentovskaya et al., 2011). (C) LPS structures of E. coli K-12 D21 and its isogenic mutants (Yu and Mizushima, ; Nikaido and Vaara, ; Razatos et al., ; Junkes et al., ; Prokhorenko et al., 2009). ^†, some sources indicate galactose (Junkes et al., 2008); ^‡, some sources indicate two or three KDO residues (Nikaido and Vaara, 1985). The table shows presence (+) or lack (−) of Ail-mediated phenotypes (autoaggregation and pellicle formation, adhesion to Hep-2 cells, internalization into Hep-2 cells, and human serum resistance) related to a particular strain (Kolodziejek et al., 2007, 2010).