Multi-Functional Characteristics of the Pseudomonas aeruginosa Type III Needle-Tip Protein, PcrV; Comparison to Orthologs in other Gram-negative Bacteria

Abstract

Pseudomonas aeruginosa possesses a type III secretion system (T3SS) to intoxicate host cells and evade innate immunity. This virulence-related machinery consists of a molecular syringe and needle assembled on the bacterial surface, which allows delivery of T3 effector proteins into infected cells. To accomplish a one-step effector translocation, a tip protein is required at the top end of the T3 needle structure. Strains lacking expression of the functional tip protein fail to intoxicate host cells. P. aeruginosa encodes a T3S that is highly homologous to the proteins encoded by Yersinia spp. The needle-tip proteins of Yersinia, LcrV, and P. aeruginosa, PcrV, share 37% identity and 65% similarity. Other known tip proteins are AcrV (Aeromonas), IpaD (Shigella), SipD (Salmonella), BipD (Burkholderia), EspA (EPEC, EHEC), Bsp22 (Bordetella), with additional proteins identified from various Gram-negative species, such as Vibrio and Bordetella. The tip proteins can serve as a protective antigen or may be critical for sensing host cells and evading innate immune responses. Recognition of the host microenvironment transcriptionally activates synthesis of T3SS components. The machinery appears to be mechanically controlled by the assemblage of specific junctions within the apparatus. These junctions include the tip and base of the T3 apparatus, the needle proteins and components within the bacterial cytoplasm. The tip proteins likely have chaperone functions for translocon proteins, allowing the proper assembly of translocation channels in the host membrane and completing vectorial delivery of effector proteins into the host cytoplasm. Multi-functional features of the needle-tip proteins appear to be intricately controlled. In this review, we highlight the functional aspects and complex controls of T3 needle-tip proteins with particular emphasis on PcrV and LcrV.

LcrV Mutants That Abolish Yersinia Type III Injectisome Function

“…These results are in agreement with earlier work identifying Sato and colleagues performed linker-scanning mutagenesis of pcrV, encoding the cap protein of Pseudomonas aeruginosa type III needles (48). Of note, PcrV and LcrV are 37% identical and 67% similar at the amino acid level, and the two proteins are presumed to assemble into structures with similar functions (43,49 (48). The linker insertions map to helices ␣7 and ␣12 of LcrV, and the insertions likely interfere with the binding of mutant PcrV to PcrG, the LcrG orthologue in P. aeruginosa (48,50).…”

Effector CD8+T Cells Are Generated in Response to an Immunodominant Epitope in Type III Effector YopE during Primary Yersinia pseudotuberculosis Infection

“…T3SSs are required by these Gram-negative bacterial pathogens for virulence (4)(5)(6)(7). T3SSs are activated upon contact of the bacteria with host cells and function to deliver effector proteins into or across the eukaryotic plasma membrane (8)(9)(10)(11)(12). Because of their ability to deliver proteins into the cytosol of host cells and to stimulate a strong innate response, T3SS-containing bacteria are being considered for use as live vaccine vectors to induce protective CD8 ϩ T cell responses against heterologous antigens (13)(14)(15).…”

Protein Export According to Schedule: Architecture, Assembly, and Regulation of Type III Secretion Systems from Plant- and Animal-Pathogenic Bacteria

“…The aim of this review is to summarize our current knowledge of the architecture of T3S systems and the control mechanisms underlying T3S in plant-and animal-pathogenic bacteria. For a detailed description of individual proteins or regulatory mechanisms, the reader is also referred to excellent previous overview articles that provide summaries on the following topics: translocation-associated T3S systems (29,72,105,161,199,217,557), flagellar T3S systems (92,161,343,377,428,549), T3S chaperones (175,431), structures and functions of individual components of T3S systems (46,70,243,281,283,349,353,389,395,482), and control mechanisms underlying T3S and gene expression (64,106,129,212,370,421,547,555,588).…”