Immunomodulatory Yersinia outer proteins (Yops)–useful tools for bacteria and humans alike

Abstract

Human-pathogenic Yersinia produce plasmid-encoded Yersinia outer proteins (Yops), which are necessary to down-regulate anti-bacterial responses that constrict bacterial survival in the host. These Yops are effectively translocated directly from the bacterial into the target cell cytosol by the type III secretion system (T3SS). Cell-penetrating peptides (CPPs) in contrast are characterized by their ability to autonomously cross cell membranes and to transport cargoindependent of additional translocation systems. The recent discovery of bacterial cellpenetrating effector proteins (CPEs) -with the prototype being the T3SS effector protein YopM -established a new class of autonomously translocating immunomodulatory proteins. CPEs represent a vast source of potential self-delivering, anti-inflammatory therapeutics. In this review, we give an update on the characteristic features of the plasmid-encoded Yops and, based on recent findings, propose the further development of these proteins for potential therapeutic applications as natural or artificial cell-penetrating forms of Yops might be of value as bacteria-derived biologics.

The TAL Effector AvrBs3 from Xanthomonas campestris pv. vesicatoria Contains Multiple Export Signals and Can Enter Plant Cells in the Absence of the Type III Secretion Translocon

“…Many Gram-negative bacterial pathogens translocate effector proteins into eukaryotic host cells to modulate host cellular pathways such as defense responses to their own benefit (Raymond et al, 2013 ; Ashida et al, 2015 ; Santos and Finlay, 2015 ; Büttner, 2016 ; Ensminger, 2016 ; Grabowski et al, 2017 ). Effector protein translocation often depends on the type III secretion (T3S) system, which is an essential pathogenicity factor of many bacterial species and is related to the bacterial flagellum (Büttner, 2012 ; Diepold and Armitage, 2015 ).…”

Editorial: The Pathogenic Yersiniae–Advances in the Understanding of Physiology and Virulence, Second Edition

“…The Ysc-Yop T3S system (T3SS) is encoded on a virulence plasmid common to all human pathogenic Yersinia (Cornelis et al, 1998). This so-called “injectisome” has long been believed to provide a conduit through which a restricted set of just six or seven plasmid-encoded host-modulating Yop effectors are delivered from the bacterial cytoplasm into the eukaryotic cell cytosol (Pha and Navarro, 2016; Grabowski et al, 2017). Using a transposon site hybridization based genome wide screen, Schesser-Bartra et al identified three chromosomally-encoded proteins that promote Y. pestis infection in cells and in mice.…”

Bacterial riboswitches and RNA thermometers: Nature and contributions to pathogenesis

“…In Yersinia pestis , an RNAT at the 5ʹ-UTR of lcrF gene was identified in the intergenic region of two-gene operon, yscW-lcrF operon [ 82 ]. LcrF is a global transcriptional activator of many virulence genes including outer membrane proteins (Yops) employed for evasion of antibacterial immune response [ 84 ] and type III secretion system [ [85] , [86] , [87] ]. Furthermore, transcription of the whole operon is also regulated by thermosensitive histone-like protein that only when melted at 37 °C allows RNAP to read-through the operon [ 82 , 88 ].…”