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.

Temperature-responsive in vitro RNA structurome of Yersinia pseudotuberculosis

“…The cytotoxic necrotizing factor CNFγ acts as toxin and is an essential virulence determinant, as it modulates inflammatory responses and counteracts attack by innate immune effectors (36,37). Similar to YadA, the adhesin AilA promotes binding to and subsequent killing of neutrophils via type III secretion-mediated translocation of effector proteins into the target host cell and promotes resistance against complement-mediated killing (38)(39)(40)(41).…”

Characterizing the virulence factor YapE in Yersinia pestis.

“…inhibition of the inflammatory response [68], 3) inhibition of the bactericidal properties of complement [68][69][70]and 4) prevention of neutrophil recruitment to the lymph nodes [69,70]. Ail has been shown to be the primary adhesin in the attachment of the T3SS to host cells in Y. pestis where its deletion exhibits significant reduction in binding to epithelial and monocytic cells [17,70].…”

“…Ail has been shown to be the primary adhesin in the attachment of the T3SS to host cells in Y. pestis where its deletion exhibits significant reduction in binding to epithelial and monocytic cells [17,70].…”

“…Interestingly, the transcription of Ail can also be altered when other outer membrane components are mutated [70]. In addition when comparative proteome strategies were used to identify new virulence targets found that Ail clustered together with virulence associated proteins on the plasmid pCD1.…”

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…pestis has several known adhesins, such as Ali, YadB, YadC, Pla and pH 6 antigen [1,26,265]. Studies of these adhesins in Y. pestis demonstrate their importance for adhering to host epithelial cells and professional phagocytes through interactions with host proteins, but clear links indicating their role in Y. pestis invasion has not been established [26,[265][266][267]. Furthermore, the Y. pestis T3SS is not used for invasion, and is actually well established to be anti-phagocytic [1].…”