scholarly journals Proteolytic processing of the Yersinia pestis YapG autotransporter by the omptin protease Pla and the contribution of YapG to murine plague pathogenesis

2013 ◽  
Vol 62 (8) ◽  
pp. 1124-1134 ◽  
Author(s):  
M. Chelsea Lane ◽  
Jonathan D. Lenz ◽  
Virginia L. Miller

Autotransporter protein secretion represents one of the simplest forms of secretion across Gram-negative bacterial membranes. Once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. Autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. To better understand the role of autotransporters in disease, our research focused on the autotransporters of Yersinia pestis, the aetiological agent of plague. Y. pestis strain CO92 has nine functional conventional autotransporters, referred to as Yaps for Yersinia autotransporter proteins. Three Yaps have been directly implicated in virulence using established mouse models of plague infection (YapE, YapJ and YapK). Whilst previous studies from our laboratory have shown that most of the CO92 Yaps are cell associated, YapE and YapG are processed and released by the omptin protease Pla. In this study, we identified the Pla cleavage sites in YapG that result in many released forms of YapG in Y. pestis, but not in the evolutionarily related gastrointestinal pathogen, Yersinia pseudotuberculosis, which lacks Pla. Furthermore, we showed that YapG does not contribute to Y. pestis virulence in established mouse models of bubonic and pneumonic infection. As Y. pestis has a complex life cycle involving a wide range of mammalian hosts and a flea vector for transmission, it remains to be elucidated whether YapG has a measurable role in any other stage of plague disease.

2012 ◽  
Vol 80 (10) ◽  
pp. 3693-3705 ◽  
Author(s):  
Jonathan D. Lenz ◽  
Brenda R. S. Temple ◽  
Virginia L. Miller

ABSTRACTYersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogenYersinia pseudotuberculosis. Both species have numerous type Va autotransporters, most of which appear to be highly conserved. InY. pestisCO92, the autotransporter genesyapKandyapJshare a high level of sequence identity. By comparingyapKandyapJto three homologous genes inY. pseudotuberculosisIP32953 (YPTB0365, YPTB3285, and YPTB3286), we show thatyapKis conserved inY. pseudotuberculosis, whileyapJis unique toY. pestis. All of these autotransporters exhibit >96% identity in the C terminus of the protein and identities ranging from 58 to 72% in their N termini. By extending this analysis to include homologous sequences from numerousY. pestisandY. pseudotuberculosisstrains, we determined that these autotransporters cluster into a YapK (YPTB3285) class and a YapJ (YPTB3286) class. The YPTB3286-like gene of mostY. pestisstrains appears to be inactivated, perhaps in favor of maintainingyapJ. Since autotransporters are important for virulence in many bacterial pathogens, includingY. pestis, any change in autotransporter content should be considered for its impact on virulence. Using established mouse models ofY. pestisinfection, we demonstrated that despite the high level of sequence identity,yapKis distinct fromyapJin its contribution to disseminatedY. pestisinfection. In addition, a mutant lacking both of these genes exhibits an additive attenuation, suggesting nonredundant roles foryapJandyapKin systemicY. pestisinfection. However, the deletion of the homologous genes inY. pseudotuberculosisdoes not seem to impact the virulence of this organism in orogastric or systemic infection models.


Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 974
Author(s):  
Irina B. Ivshina ◽  
Maria S. Kuyukina ◽  
Anastasiia V. Krivoruchko ◽  
Elena A. Tyumina

Under conditions of increasing environmental pollution, true saprophytes are capable of changing their survival strategies and demonstrating certain pathogenicity factors. Actinobacteria of the genus Rhodococcus, typical soil and aquatic biotope inhabitants, are characterized by high ecological plasticity and a wide range of oxidized organic substrates, including hydrocarbons and their derivatives. Their cell adaptations, such as the ability of adhering and colonizing surfaces, a complex life cycle, formation of resting cells and capsule-like structures, diauxotrophy, and a rigid cell wall, developed against the negative effects of anthropogenic pollutants are discussed and the risks of possible pathogenization of free-living saprotrophic Rhodococcus species are proposed. Due to universal adaptation features, Rhodococcus species are among the candidates, if further anthropogenic pressure increases, to move into the group of potentially pathogenic organisms with “unprofessional” parasitism, and to join an expanding list of infectious agents as facultative or occasional parasites.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.


Talanta ◽  
2021 ◽  
pp. 122640
Author(s):  
Bin Feng ◽  
Liyuan Shi ◽  
Haipeng Zhang ◽  
Haimei Shi ◽  
Chuanfan Ding ◽  
...  

2010 ◽  
Vol 192 (16) ◽  
pp. 4239-4245 ◽  
Author(s):  
Guangchun Bai ◽  
Andrey Golubov ◽  
Eric A. Smith ◽  
Kathleen A. McDonough

ABSTRACT Yersinia pestis, the etiologic agent of plague, has only recently evolved from Yersinia pseudotuberculosis. hfq deletion caused severe growth restriction at 37°C in Y. pestis but not in Y. pseudotuberculosis. Strains from all epidemic plague biovars were similarly affected, implicating Hfq, and likely small RNAs (sRNAs), in the unique biology of the plague bacillus.


2008 ◽  
Vol 57 (3) ◽  
pp. 324-331 ◽  
Author(s):  
Alvin Stewart ◽  
Benjamin Satterfield ◽  
Marissa Cohen ◽  
Kim O'Neill ◽  
Richard Robison

Yersinia pestis, the aetiological agent of the plague, causes sporadic disease in endemic areas of the world and is classified as a National Institute of Allergy and Infectious Diseases Category A Priority Pathogen because of its potential to be used as a bioweapon. Health departments, hospitals and government agencies need the ability to rapidly identify and characterize cultured isolates of this bacterium. Assays have been developed to perform this function; however, they are limited in their ability to distinguish Y. pestis from Yersinia pseudotuberculosis. This report describes the creation of a real-time PCR assay using Taqman probes that exclusively identifies Y. pestis using a unique target sequence of the yihN gene on the chromosome. As with other Y. pestis PCR assays, three major genes located on each of the three virulence plasmids were included: lcrV on pCD1, caf1 on pMT1 and pla on pPCP1. The quadruplex assay was validated on a collection of 192 Y. pestis isolates and 52 near-neighbour isolates. It was discovered that only 72 % of natural plague isolates from the states of New Mexico and Utah harboured all three virulence plasmids. This quadruplex assay proved to be 100 % successful in differentiating Y. pestis from all near neighbours tested and was able to reveal which of the three virulence plasmids a particular isolate possessed.


Microbiology ◽  
2009 ◽  
Vol 155 (1) ◽  
pp. 198-209 ◽  
Author(s):  
Scott W. Bearden ◽  
Christopher Sexton ◽  
Joshua Pare ◽  
Janet M. Fowler ◽  
Cindy G. Arvidson ◽  
...  

It is established that Yersinia pestis, the causative agent of bubonic plague, recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing chromosomal degeneration while acquiring two unique plasmids that facilitate tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague bacilli spread from central Asia to sylvatic foci throughout the world. These epidemic isolates exhibit a broad host range including man as opposed to enzootic (pestoides) variants that remain in ancient reservoirs where infection is limited to muroid rodents. Cells of Y. pseudotuberculosis are known to express glucose-6-phosphate dehydrogenase (Zwf) and aspartase (AspA); these activities are not detectable in epidemic Y. pestis due to missense mutations (substitution of proline for serine at amino position 155 of Zwf and leucine for valine at position 363 of AspA). In this study, functional Zwf was found in pestoides strains E, F and G but not seven other enzootic isolates; enzymic activity was associated with retention of serine at amino acid position 155. Essentially, full AspA activity occurred in pestoides isolates where valine (pestoides A, B, C and D) or serine (pestoides E, F, G and I) occupied position 363. Reduced activity occurred in strains Angola and A16, which contained phenylalanine at this position. The k cat but not K m of purified AspA from strain Angola was significantly reduced. In this context, aspA of the recently described attenuated enzootic microtus biovar encodes active valine at position 363, further indicating that functional AspA is a biomarker for avirulence of Y. pestis in man.


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