Pathogenicity and virulence of Yersinia.

The genus Yersinia includes human, animal, insect, and plant pathogens as well as many symbionts and harmless bacteria. Within this genus are Yersinia enterocolitica and the Yersinia pseudotuberculosis complex, with four human pathogenic species that are highly related at the genomic level including the causative agent of plague, Yersinia pestis. Extensive laboratory, field work, and clinical research have been conducted to understand the underlying pathogenesis and zoonotic transmission of these pathogens. There are presently more than 500 whole genome sequences from which an evolutionary footprint can be developed that details shared and unique virulence properties. Whereas the virulence of Y. pestis now seems in apparent homoeostasis within its flea transmission cycle, substantial evolutionary changes that affect transmission and disease severity continue to ndergo apparent selective pressure within the other Yersiniae that cause intestinal diseases. In this review, we will summarize the present understanding of the virulence and pathogenesis of Yersinia, highlighting shared mechanisms of virulence and the differences that determine the infection niche and disease severity.

Mechanism of sturgeon intestinal inflammation induced by Yersinia ruckeri and the effect of florfenicol intervention.

The mechanism by which Y. ruckeri infection induces enteritis in Chinese sturgeon remains unclear, and the efficacy of drug prevention and control measures is not only poor but also plagued with numerous issues. We conducted transcriptomic and 16 S rRNA sequencing analyses to examine the differences in the intestinal tract of hybrid sturgeon before and after Y. ruckeri infection and florfenicol intervention. Our findings revealed that Y. ruckeri induced the expression of multiple inflammatory factors, including il1ß, il6, and various chemokines, as well as casp3, casp8, and multiple tumor necrosis factor family members, resulting in pathological injury to the body. Additionally, at the phylum level, the relative abundance of Firmicutes and Bacteroidota increased, while the abundance of Plesiomonas and Cetobacterium decreased at the genus level, altering the composition of the intestinal flora. Following florfenicol intervention, the expression of multiple apoptosis and inflammation-related genes was down-regulated, promoting tissue repair. However, the flora became further dysregulated, increasing the risk of infection. In conclusion, our analysis of the transcriptome and intestinal microbial composition demonstrated that Y. ruckeri induces intestinal pathological damage by triggering apoptosis and altering the composition of the intestinal microbiota. Florfenicol intervention can repair pathological damage, but it also exacerbates flora imbalance, leading to a higher risk of infection. These findings help elucidate the molecular mechanism of Y. ruckeri-induced enteritis in sturgeon and evaluate the therapeutic effect of drugs on intestinal inflammation in sturgeon.

The implication of viability and pathogenicity by truncated lipopolysaccharide in Yersinia enterocolitica.

The fast envelope stress responses play a key role in the transmission and pathogenesis of Yersinia enterocolitica, one of the most common foodborne pathogens. Our previous study showed that deletion of the waaF gene, essential for the biosynthesis of lipopolysaccharide (LPS) core polysaccharides, led to the formation of a truncated LPS structure and induced cell envelope stress. This envelope stress may disturb the intracellular signal transduction, thereby affecting the physiological functions of Y. enterocolitica. In this study, truncated LPS caused by waaF deletion was used as a model of envelope stress in Y. enterocolitica. We investigated the mechanisms of envelope stress responses and the cellular functions affected by truncated LPS. Transcriptome analysis and phenotypic validation showed that LPS truncation reduced flagellar assembly, bacterial chemotaxis, and inositol phosphate metabolism, presenting lower pathogenicity and viability both in vivo and in vitro environments. Further 4D label-free phosphorylation analysis confirmed that truncated LPS perturbed multiple intracellular signal transduction pathways. Specifically, a comprehensive discussion was conducted on the mechanisms by which chemotactic signal transduction and Rcs system contribute to the inhibition of chemotaxis. Finally, the pathogenicity of Y. enterocolitica with truncated LPS was evaluated in vitro using IPEC-J2 cells as models, and it was found that truncated LPS exhibited reduced adhesion, invasion, and toxicity of Y. enterocolitica to IPEC-J2 cells. Our research provides an understanding of LPS in the regulation of Y. enterocolitica viability and pathogenicity and, thus, opening new avenues to develop novel food safety strategies or drugs to prevent and control Y. enterocolitica infections. KEY POINTS: • Truncated LPS reduces flagellar assembly, chemotaxis, and inositol phosphate metabolism in Y. enterocolitica. • Truncated LPS reduces adhesion, invasion, and toxicity of Y. enterocolitica to IPEC-J2 cells. • Truncated LPS regulates intracellular signal transduction of Y. enterocolitica.

Exploring Yersinia ruckeri (O1 Biotype 2) infection in three early life-stages of rainbow trout.

Enteric redmouth disease (ERM) caused by the enterobacterium Yersinia ruckeri poses a significant threat to salmonid aquaculture globally. Despite decades of experimental infection studies, key knowledge gaps remain regarding the onset of disease susceptibility and mechanisms of immunity during early developmental stages, undermining disease management efforts in all susceptible life-stages. In this study, a series of immersion challenges were conducted, challenging and re-challenging rainbow trout Oncorhynchus mykiss (Walbaum) at 7, 14 and 51 d post-hatch (dph; mean weights = 0.085, 0.1 and 2.0 g respectively) to high concentrations (1.72 × 107-1.1 × 108 CFU) of Y. ruckeri at 15°C. This study indicates the hitherto unknown initial point of susceptibility to infection as the time of first ingestion of exogenous food (14 dph), and shows that individuals surviving primary challenge at 14 dph are significantly more likely to survive re-challenge at 51 dph compared with naive individuals (hazard ratio = 1.446, p = 0.032). Other key findings include large variation in mortality between different development-stages, from 21.1% at 14 dph to 81.2% at 51 dph, and novel age-dependent symptoms not reported previously. Results from this study enhance our understanding of ERM in juvenile rainbow trout and inform the development of improved aquatic animal health management strategies, thereby contributing to the productivity and sustainability of salmonid aquaculture into the future.

Characterization of phenyl propiolic acid from Proteus mirabilis DMTMMR-11 and Evaluation of its mode of action against Yersinia enterocolitica (MTCC-840) an in-Vitro and in-Vivo based approach.

Foodborne illnesses are pervasive in raising public health concerns in both developed and developing nations. Yersinia enterocolitica a zoonotic bacterial species that causes food-transmitted infections, and gastroenteritis, is its most prevalent clinical manifestation. This study aims to investigate the differences, dependencies, and inhibitory mechanisms between the host and the microbiome. Proteus mirabilis DMTMMR-11, the bacterium found in the human gastrointestinal tract was used for the extraction of intracellular metabolite, because of its beneficial effects on the normal flora of the human gut. Phenyl propiolic acid was identified as the dominant compound in the metabolite after characterization using FT-IR, NMR, and LC-MS-MS. To assess its inhibitory mechanism against Yersinia enterocolitica, the pathogen was subjected to biological characterization by MBC and MIC, resulting in the rate of inhibition at 50 µg/ml. Anti-bacterial curve supports the inhibited growth of Y. enterocolitica. Mechanism of inhibition at its cellular level was indicated by the increase in alkaline phosphate content, which drastically reduced the cell membrane and cell wall potential expanding its permeability by intruding the membrane proteins, which was observed in SEM Imaging. Phenyl propiolic acid efficiently disrupts the biofilm formation by reducing the adherence and increasing the eradication property of the pathogen by exhibiting 65% of inhibition at the minimal duration of 12h. In-vivo study was carried out through host-pathogen interaction in C. elegans, an efficient model organism assessed for its life-span, physiological, and behavioral assays.

Comprehensive Analysis of YTH Domain-Containing Genes, Encoding m6A Reader and Their Response to Temperature Stresses and Yersinia ruckeri Infection in Rainbow Trout (Oncorhynchus mykiss).

YTH domain-containing genes are important readers of N6-methyladenosine (m6A) modifications with ability to directly affect the fates of distinct RNAs in organisms. Despite their importance, little is known about YTH domain-containing genes in teleosts until now. In the present study, a total of 10 YTH domain-containing genes have been systematically identified and functionally characterized in rainbow trout (Oncorhynchus mykiss). According to the phylogenetic tree, gene structure and syntenic analysis, these YTH domain-containing genes could be classified into three evolutionary subclades, including YTHDF, YTHDC1 and YTHDC2. Of them, the copy number of OmDF1, OmDF2, OmDF3, and OmDC1 were duplicated or even triplicated in rainbow trout due to the salmonid-specific whole-genome duplication event. The three-dimensional protein structure analysis revealed that there were similar structures and the same amino acid residues that were associated with cage formation between humans and rainbow trout, implying their similar manners in binding to m6A modification. Additionally, the results of qPCR experiment indicated that the expression patterns of a few YTH domain-containing genes, especially OmDF1b, OmDF3a and OmDF3b, were significantly different in liver tissue of rainbow trout under four different temperatures (7 °C, 11 °C, 15 °C, and 19 °C). The expression levels of OmDF1a, OmDF1b and OmDC1a were obviously repressed in spleen tissue of rainbow trout at 24 h after Yersinia ruckeri infection, while increased expression was detected in OmDF3b. This study provides a systemic overview of YTH domain-containing genes in rainbow trout and reveals their biological roles in responses to temperature stress and bacterial infection.

Controlled Experimental Infection in Pigs with a Strain of Yersinia enterocolitica Harboring Genetic Markers for Human Pathogenicity: Colonization and Stability.

Yersinia enterocolitica (Ye) is one of the major causes of foodborne zoonosis. The BT4/O:3 bioserotype is most commonly isolated in human infections. Pigs are considered the main reservoir of Ye, and hence, understanding the dynamics of infection by this pathogen at the individual and group levels is crucial. In the present study, an experimental model was validated in Large White pigs infected with a BT4/O:3 strain. This study showed that Ye contamination in pigs may occur via the introduction of the bacteria not only by mouth but also by snout, with a colonization process consisting of three periods corresponding to three contamination statuses of pigs: P1, corresponding to the 24 h following ingestion or inhalation of Ye with the appearance of bacteria in tonsils or in feces; P2, from 2 days postinoculation (dpi), corresponding to expansion of Ye and colonization of the digestive system and extraintestinal organs associated with an IgG serological response; and P3, after 21 dpi, corresponding to regression of colonization with intermittent Ye detection in tonsils and feces. Although the inoculated strain persisted up to 56 dpi in all pigs, genetic variations with the loss of the gene yadA (a gene involved in human infection) and the emergence of two new multilocus variable-number tandem-repeat analysis (MLVA) profiles were observed in 33% of the 30 isolates studied. This experimental infection model of pigs by Ye provides new insights into the colonization steps in pigs in terms of bacterial distribution over time and bacterial genetic stability.

Diarrhoea-causing microorganisms are rare in adult patients undergoing diagnostic laparoscopy for suspected appendicitis: a prospective observational cohort study.

We investigated if diarrhoea-causing bacteria, including Yersinia species, could mimic the symptoms of appendicitis and lead to surgery. This prospective observational cohort study (NCT03349814) included adult patients undergoing surgery for suspected appendicitis. Rectal swabs were analysed with polymerase chain reaction (PCR) for Yersinia, Campylobacter, Salmonella, Shigella and Aeromonas spp. Blood samples were analysed routinely and with an in-house ELISA serological test for Yersinia enterocolitica antibodies. We compared patients without appendicitis and patients with appendicitis confirmed by histopathology. The outcomes included PCR-confirmed infection with Yersinia spp., serologic-confirmed infection with Y. enterocolitica, PCR-confirmed infection with other diarrhoea-causing bacteria and Enterobius vermicularis confirmed by histopathology. A total of 224 patients were included, 51 without and 173 with appendicitis, and followed for 10 days. PCR-confirmed infection with Yersinia spp. was found in one patient (2%) without appendicitis and no patients (0%) with appendicitis (p = 0.23). Serology was positive for Y. enterocolitica for the same patient without appendicitis and two patients with appendicitis (p = 0.54). Campylobacter spp. were detected in 4% vs 1% (p = 0.13) of patients without and with appendicitis, respectively. Infection with Yersinia spp. and other diarrhoea-causing microorganisms in adult patients undergoing surgery for suspected appendicitis was rare.

Yersinia enterocolitica in Crohn's disease.

Increasing attention is being paid to the unique roles gut microbes play in both physiological and pathological processes. Crohn's disease (CD) is a chronic, relapsing, inflammatory disease of the gastrointestinal tract with unknown etiology. Currently, gastrointestinal infection has been proposed as one initiating factor of CD. Yersinia enterocolitica, a zoonotic pathogen that exists widely in nature, is one of the most common bacteria causing acute infectious gastroenteritis, which displays clinical manifestations similar to CD. However, the specific role of Y. enterocolitica in CD is controversial. In this Review, we discuss the current knowledge on how Y. enterocolitica and derived microbial compounds may link to the pathogenesis of CD. We highlight examples of Y. enterocolitica-targeted interventions in the diagnosis and treatment of CD, and provide perspectives for future basic and translational investigations on this topic.

[Relationship between Serotypes and Biotypes of Yersinia enterocolitica and the Names of Identified Bacteria in the Microbial Identification and Susceptibility Testing Devices].

Yersinia enterocolitica is a causative agent of food poisoning and has been isolated from pork and stream water, causing Yersinia enterocolitica in humans. The bacterium is divided into multiple serotypes and biotypes, among which serotypes O3 and O8 and biotypes 1B, 3, and 4 are frequently isolated in Japan. Biotype 3 can be classified as [VP+, Suc+], [VP-, Suc+], [VP-, Suc-] based on the biochemical properties. Among them, [O3, 3, VP-, Suc-] has been reported to be identified as Yersinia kristensenii in a simple identification kit. An increasing number of facilities in the field of microbiological testing are currently using mass spectrometers to identify species of microorganisms. However, there are many facilities where mass spectrometers have not yet been installed and microbial identification and susceptibility testing devices are used to identify bacterial species. No reports have described how the [O3, 3, VP-, Suc-] type, which is identified as Y. kristensenii in the simple identification kit, is identified by the microbial identification and susceptibility testing devices. In this study, 15 strains of Y. enterocolitica, which were previously isolated, serotyped, and biotyped from fecal culture tests at our hospital, were analyzed to see how these strains were identified in RAISUS S4, Microscan WalkAway, VITEK2 Blue, and BD Phoenix. [O3, 3, VP-, Suc-] was identified as Y. kristensenii in RAISUS S4, Microscan WalkAway, and VITEK2 Blue and as Y. enterocolitica in BD Phoenix. [O3, 3, VP-, Suc+], [O3, 4] and [O8, 1B] were identified as Y. enterocolitica. Therefore, when a sample was identified as Y. kristensenii by RAISUS S4, Microscan WalkAway, or VITEK2 Blue, the possibility that it was actually [O3, 3, VP-, Suc-] could not be ruled out. The possibility of Y. enterocolitica should be informed to attending physicians.

Inhibitory effect of protocatechualdehyde on Yersinia enterocolitica and its critical virulence factors.

Yersinia enterocolitica (Y. enterocolitica) is a gastrointestinal pathogen that is distributed worldwide, involved in systemic, extraintestinal and invasive infections in immunocompromised patients. Establishment of antibiotic resistance in the pathogen has produced a need for new antibacterial agents. The purpose of this study was to elucidate antibacterial mechanism of protocatechualdehyde (PCA) extracted from the roots of Salvia miltiorrhiza towards Y. enterocolitica, and to investigate effects of PCA on key virulence factors associated with human infection. Present results indicated that PCA exerted its antibacterial activity against Y. enterocolitica mainly by the rapid rise of intracellular reactive oxygen species, leading to change in permeability and integrity of cell membrane, and ultimately decline of membrane potential and intracellular ATP. Furthermore, scanning electron microscopic analysis revealed that Y. enterocolitica presented gradually shrinkage in length and partial wrinkles upon PCA treatment. PCA also effectively decreased motility, biofilm formation, quorum sensing in a dose-dependent manner without affecting bacterial growth. Further, at SICs, PCA substantially suppressed the adhesion and invasion of Y. enterocolitica to HT-29 cells and the downregulation of essential virulence factor-encoding genes unveiled impaired virulence. Overall, the findings revealed the potential of PCA as an alternative antibacterial agent to combat Y. enterocolitica contamination and infections.

[History of reactive arthritis. Historical milestones and future]. / Geschichte der reaktiven Arthritis. Historische Meilensteine und Zukunft.

The introduction of the term reactive arthritis (ReA) for the joint inflammation observed after infection with Yersinia enterocolitica, in which "a causative pathogen cannot be isolated from the synovial fluid", and the association with the HLA-B27 were the historical milestones for a new classification and assignment to the spondylarthritides (SpA). The division into postinfectious and reactive arthritis proposed in 1976 was put into perspective in the 1990s because of investigations with the newly available molecular biological method of the polymerase chain reaction. Microbial products could be identified from joint samples of patients with ReA. Therefore, it was proposed to abandon the distinction between the two groups of diseases and to prefer the term ReA for both. This created a terminological and nosological issue. On the one hand, there are generally accepted classification and diagnostic criteria for the classical HLA-B27-associated ReA that are assigned to SpA. On the other hand, an increasing number of bacterial pathogens, viruses, amoebas, helminths as well as antiviral and antibacterial vaccinations are described as triggers of arthritis, which have been published under the term ReA. Since the beginning of the SARS-CoV­2 pandemic, cases of acute post-COVID-19 arthritis have been described, which were also classified as ReA because of comparable clinical features.

Prevalence, virulence determinants, and genetic diversity in Yersinia enterocolitica isolated from slaughtered pigs and pig carcasses.

Yersinia enterocolitica is an important zoonotic foodborne pathogen that could be transferred from infected pigs to their carcasses at slaughter, with subsequent introduction of the pathogen into the food chain. The aim of the present study was to study the prevalence, virulence characteristics, and genetic diversity of Y. enterocolitica isolates present in slaughtered pig tonsils and carcasses by using the WGS approach. A total of 200 slaughtered pig tonsils from 11 pig farms were collected in 2020-2021 at six slaughterhouses located in Latvia. Out of these samples, n = 190 were obtained from slaughtered pigs raised on Latvian farms while n = 10 were of Lithuanian origin, with the number of farms sampled being 10 and 1, respectively. Additionally, 30 pig carcasses were sampled at five slaughterhouses from pigs originating from five farms in 2021. Samples were investigated microbiologically, Y. enterocolitica isolates were biotyped and serotyped. Y. enterocolitica 4/O:3 was screened for antimicrobial resistance with the EUVSEC test panels. Whole genome sequence analysis (WGS) was performed in order to detect virulence genes and to assess the genetic diversity of Y. enterocolitica isolates. A total of 139 isolates, including one to three isolates from 84 Y. enterocolitica positive slaughtered pig tonsils and 13 pig carcass samples, were subjected to WGS analysis. The prevalence of Y. enterocolitica 4/O:3 in slaughtered pig tonsils and carcasses was 35% (70/200) and 13% (4/30), respectively. Antimicrobial resistance to ampicillin and tetracycline was detected in 97% (72/74) and 1% (1/74) of Y. enterocolitica 4/O:3 isolates. Y. enterocolitica 4/O:3 was represented only by ST18, while Y. enterocolitica 1A by ST3, ST147, ST304, ST307, and ST473. The ST18 isolates harbored the same main chromosomal (ail, inv, myfA, ystA) and majority shared plasmid-borne virulence genes (virF, yadA, yop virulon). The main virulence genes were not identified within the STs of Y. enterocolitica 1A and only minor differences were found between ST3, ST147, ST304, ST307, and ST473. Among ST18 isolates, cgMLST analysis revealed 43 cgMLST genotypes while 16 cgMLST genotypes were found among Y. enterocolitica 1A STs. The present study has shown the distribution of genetically distant cgMLST genotypes in slaughtered pigs from pig farms located in different geographical regions of Latvia, with one to 11 cgMLSTs identified within each sampled farm. The presence of undistinguishable cgMLST genotypes in slaughtered pig tonsils and the respective carcasses supported the link between the slaughter of Y. enterocolitica - positive pigs and carcass contamination with Y. enterocolitica 4/O:3.

Differentiation of Yersinia enterocolitica enteritis from other bacterial enteritides by ultrasonography: A single-center case-control study.

BACKGROUND: The diagnosis of Yersinia enterocolitica (Ye) enteritis is not easy because detection from stool culture is more difficult for Ye than for other bacterial enteritides. The establishment of characteristic ultrasonographic findings for Ye enteritis would help improve the detection rate of Ye enteritis along with performance of several cold cultures. This would facilitate appropriate selection of antibiotics based on antimicrobial susceptibility testing and contribute to a more accurate understanding of local public health. This study aimed to retrospectively compare ultrasonographic findings and clinical features between children with Ye enteritis and other bacterial enteritides. METHODS: We identified patients treated for Ye enteritis (Ye group; n = 27) or other bacterial enteritides (Other enteritis group; n = 29) between 2014 and 2018. Ultrasonographic findings (including mean maximum diameter and mean major-minor axis ratio of ileocecal lymph nodes, wall thickness of the terminal ileum, and presence of a pericecal hyperechoic region), clinical symptoms, and laboratory findings at first visit were compared between groups. RESULTS: No difference in mean maximum diameter of ileocecal lymph nodes was seen between groups. However, mean major-minor axis ratio of ileocecal lymph nodes was lower in the Ye group than in the Other enteritis group (p < 0.001). Presence of a pericecal hyperechoic region was more frequent in the Ye group than in the Other enteritis group (p < 0.001). The combined presence of a mean ileocecal lymph node major-minor axis ratio <1.51 and a pericecal hyperechoic region offered 100% sensitivity. CONCLUSION: Characteristic ultrasonographic findings identified in this study may improve ultrasonographic differentiation of Y. enterocolitica enteritis from other bacterial enteritides.

Comparative genomics and antibiotic resistance of Yersinia enterocolitica obtained from a pork production chain and human clinical cases in Brazil.

Previous work found a high similarity of macro-restriction patterns for isolates of Yersinia enterocolitica 4/O:3 obtained at a pork production chain from Minas Gerais, Brazil. Herein we aimed to determine the clonality and the antibiotic resistance profiles of a subset of these isolates (n = 23) and human clinical isolates (n = 3). Analysis based on whole genome sequencing (WGS) showed that the isolates were distributed into two major clades based on single nucleotide polymorphisms (SNP) with one isolate defining Clade A (isolate R31) and remaining isolates (n = 25, 96.2%) defining Clade B. Seven clonal groups were identified. The inclusion of isolate R31 as a distinct clonal group was due to the presence of several phage-related genes, allowing its characterization as serotype O:5 by WGS. Disk-diffusion assays (14 antibiotics) identified 13 multidrug resistant isolates (50.0%). Subsequent sequence analysis identified 17 different antibiotic resistance related genes. All isolates harbored blaA (y56 beta-lactamase), vatF, rosA, rosB and crp, while nine isolates harbored a high diversity of antibiotic resistance related genes (n = 13). The close genetic relationship among Y. enterocolitica obtained from a pork production chain and human clinical isolates in Brazil was confirmed, and we can highlight the role of swine in the potential transmission of an antibiotic-resistant clones of a pathogenic bio-serotype to humans, or the transmission of these resistant bacteria from people to animals. The role of veterinary antibiotic use in this process is unclear.

Integrative analyses of probiotics, pathogenic infections and host immune response highlight the importance of gut microbiota in understanding disease recovery in rainbow trout (Oncorhynchus mykiss).

AIMS: Given the pivotal role played by the gut microbiota in regulating the host immune system, great interest has arisen in the possibility of controlling fish health by modulating the gut microbiota. Hence, there is a need to better understand of the host-microbiota interactions after disease responses to optimize the use of probiotics to strengthen disease resilience and recovery. METHODS AND RESULTS: We tested the effects of a probiotic feed additive in rainbow trout and challenged the fish with the causative agent for enteric red mouth disease, Yersinia ruckeri. We evaluated the survival, host immune gene expression and the gut microbiota composition. Results revealed that provision of probiotics and exposure to Y. ruckeri induced immune gene expression in the host, which were associated with changes in the gut microbiota. Subsequently, infection with Y. ruckeri had very little effect on microbiota composition when probiotics were applied, indicating that probiotics increased stabilisation of the microbiota. Our analysis revealed potential biomarkers for monitoring infection status and fish health. Finally, we used modelling approaches to decipher interactions between gut bacteria and the host immune gene responses, indicating removal of endogenous bacteria elicited by non-specific immune responses. CONCLUSIONS: We discuss the relevance of these results emphasizing the importance of host-microbiota interactions, including the protective potential of the gut microbiota in disease responses. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results highlight the functional consequences of probiotic-induced changes in the gut microbiota post infection and the resulting host immune response.

Yersinia remodels epigenetic histone modifications in human macrophages.

Various pathogens systematically reprogram gene expression in macrophages, but the underlying mechanisms are largely unknown. We investigated whether the enteropathogen Yersinia enterocolitica alters chromatin states to reprogram gene expression in primary human macrophages. Genome-wide chromatin immunoprecipitation (ChIP) seq analyses showed that pathogen-associated molecular patterns (PAMPs) induced up- or down-regulation of histone modifications (HMod) at approximately 14500 loci in promoters and enhancers. Effectors of Y. enterocolitica reorganized about half of these dynamic HMod, with the effector YopP being responsible for about half of these modulatory activities. The reorganized HMod were associated with genes involved in immune response and metabolism. Remarkably, the altered HMod also associated with 61% of all 534 known Rho GTPase pathway genes, revealing a new level in Rho GTPase regulation and a new aspect of bacterial pathogenicity. Changes in HMod were associated to varying degrees with corresponding gene expression, e. g. depending on chromatin localization and cooperation of the HMod. In summary, infection with Y. enterocolitica remodels HMod in human macrophages to modulate key gene expression programs of the innate immune response.

Heightened Virulence of Yersinia Is Associated with Decreased Function of the YopJ Protein.

Despite the maintenance of YopP/J alleles throughout the human-pathogenic Yersinia lineage, the benefit of YopP/J-induced phagocyte death for Yersinia pathogenesis in animals is not obvious. To determine how the sequence divergence of YopP/J has impacted Yersinia virulence, we examined protein polymorphisms in this type III secreted effector protein across 17 Yersinia species and tested the consequences of polymorphism in a murine model of subacute systemic yersiniosis. Our evolutionary analysis revealed that codon 177 has been subjected to positive selection; the Yersinia enterocolitica residue had been altered from a leucine to a phenylalanine in nearly all Yersinia pseudotuberculosis and Yersinia pestis strains examined. Despite this change being minor, as both leucine and phenylalanine have hydrophobic side chains, reversion of YopJF177 to the ancestral YopJL177 variant yielded a Y. pseudotuberculosis strain with enhanced cytotoxicity toward macrophages, consistent with previous findings. Surprisingly, expression of YopJF177L in the mildly attenuated ksgA- background rendered the strain completely avirulent in mice. Consistent with this hypothesis that YopJ activity relates indirectly to Yersinia pathogenesis in vivo, ksgA- strains lacking functional YopJ failed to kill macrophages but actually regained virulence in animals. Also, treatment with the antiapoptosis drug suramin prevented YopJ-mediated macrophage cytotoxicity and enhanced Y. pseudotuberculosis virulence in vivo. Our results demonstrate that Yersinia-induced cell death is detrimental for bacterial pathogenesis in this animal model of illness and indicate that positive selection has driven YopJ/P and Yersinia evolution toward diminished cytotoxicity and increased virulence, respectively.

Tissue-specific differences in detection of Yersinia ruckeri carrier status in rainbow trout (Oncorhynchus mykiss).

Effective monitoring for subclinical infections is a cornerstone of proactive disease management in aquaculture. Salmonid fish that survive enteric redmouth disease (ERM) can carry Yersinia ruckeri as a latent infection for several months, potentially facilitating cryptic spread between facilities that exchange fish. In this study, fingerling rainbow trout (Oncorhynchus mykiss) were infected by immersion and sampled for up to 14 weeks post-infection. Yersinia ruckeri was cultured from the posterior kidney of more than 89% of fish up to 4 weeks post-infection, but from 2% or fewer of fish sampled at later time points. In contrast, qPCR-based detection of the Y. ruckeri 16s rRNA gene in intestine and spleen extracts revealed a much higher rate of infection: at 14 weeks post-infection Y. ruckeri was detected in nearly 50% of spleens and 15% of intestines. The difference between spleen and intestine is likely due at least in part to technical limitations of qPCR on intestinal DNA extracts; accordingly, we propose that qPCR of spleen DNA ought to be considered the preferred standard for detection of carriers of Y. ruckeri.

Pathogenic potential and antibiotic resistance of Yersinia enterocolitica, a foodborne pathogen limited to swine tonsils in a pork production chain from Southern Brazil.

In this study, we aimed to characterize the distribution of Yersinia enterocolitica in a pork production chain in Brazil, as well as the virulence profile and antibiotic resistance of the obtained isolates. Samples from 10 pig lots obtained from finishing farms (water, feed, and barn floors, n = 30), slaughterhouse (lairage floors, carcasses at four processing steps, tonsils, and mesenteric lymph nodes, n = 610), and processing (end cuts, processing environment, n = 160) were obtained in Paraná state, Brazil, and subjected to Y. enterocolitica detection by ISO 10,273. The obtained isolates were identified based on biochemical and molecular features (16 s rRNA, inv, bioserotyping) and subjected to PCR assays to detect virulence (ail, ystA, ystB, virF, myfA, fepA, fepD, fes, tccC, ymoA, hreP, and sat) and multidrug resistance-related genes (emrD, yfhD, and marC). Also, isolates were subjected to disk diffusion test to characterize their resistance against 17 antibiotics from 11 classes and to pulsed field gel electrophoresis (PFGE) after XbaI macro-restriction. Y. enterocolitica was detected in a single sample (tonsil), and the obtained three isolates were characterized as serotype O:3, harboring ail, ystA, virF, myfA, tccC, ymoA, hreP, emrD, yfhD, and marC, and resistant to all tested antibiotics. The three isolates presented identical macro-restriction profiles by PFGE, also identical to isolates obtained from Minas Gerais, other Brazilian state; one selected isolate was identified as biotype 4. Despite the low occurrence of Y. enterocolitica in the studied pork production, the virulence potential and the antibiotic resistance profiles of the isolates demonstrated their pathogenic potential, and the macro-restriction profiles indicate strains descending from a common subtype in the pork production chain of two Brazilian States.