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The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail . These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens.

The attachment–invasion locus protein Ail of pathogenic Yersinia strains is an important virulence factor, both for invasion of eucaryotic cells and for serum resistance. In other Yersinia strains, e.g., those belonging to biotype (BT) 1A of Yersinia enterocolitica, ail has only occasionally been described. Sequence analysis of 370 BT 1A isolates in our laboratory revealed 41 (11.1%) which were ail-positive. Most of these isolates were recovered from minced meat and tonsils of wild boars, and belonged to 17 MLST allele profiles. A closer look at DNA sequences surrounding ail disclosed that the gene in most isolates is embedded in DNA regions encoding phage proteins. The genomes of four prophages belonging to four different phylogenetic clusters were determined and analyzed by in silico studies. These have sizes of 34.9 and 50.7 kb, and are closely related to each other but not to known phages. Unlike other regions of the prophages, the integrases and attachment sites of some of them diverge, leading to different integration sites in the isolates. In a fifth cluster, ail is relocated at a position on the Y. enterocolitica chromosome that is several hundred kilobases apart from those of the other clusters, but surrounded by prophage-related sequences. In addition, highly pathogenic 1B/O:8 strains contain a DNA segment which includes ail and is 65 to 94% identical to the prophage sequences determined in this study.

Yersinia enterocolitica is a significant foodborne pathogen causing gastrointestinal illnesses worldwide. This study investigates the prevalence and genomic characteristics of Y . enterocolitica to assess potential health risks in southeastern China, a region lacking mandatory yersiniosis monitoring. From 2939 samples collected between 2008 and 2022, 105 isolates were recovered. The highest prevalence was found in rodents (8.1%), followed by retail meats (7.1%), other foods (3.7%), and human clinical cases (0.8%). In addition to meats and rodents, ready-to-eat salads, seafood, and frozen food products were identified as potential transmission vehicles. Various bioserotypes and sequence types (STs) was identified, including twelve previously unreported STs. Biotype 1A, exhibiting greater genetic diversity than more pathogenic biotypes (3 and 4), was frequently found in human clinical cases. Phylogenetic analysis revealed two main lineages, with isolates primarily clustered by biotype and pathogenic traits. Antimicrobial susceptibility testing revealed 46.7% (49/105) of isolates were multidrug resistant (MDR), with frequent resistance to polymyxin B (100%), azithromycin (50.5%), and sulfanilamide isoxazole (31.4%). These findings highlight the ecological complexity and diversity of Y . enterocolitica , especially non-pathogenic biotype 1A strains, and underscore the need for enhanced food safety and antimicrobial stewardship to mitigate the public health impact of Y . enterocolitica infections. Key points Biotype 1 A strains exhibited greater genetic diversity than pathogenic biotypes. Pathogenic strains were mainly associated with lineage HC1490_2, not HC1490_10. Higher MDR levels were observed in biotype 3 and 4 strains.

Receptor-interacting protein kinase-1 (RIPK1), a master regulator of cell fate decisions, was identified as a direct substrate of MAPKAP kinase-2 (MK2) by phosphoproteomic screens using LPS-treated macrophages and stress-stimulated embryonic fibroblasts. p38 /MK2 interact with RIPK1 in a cytoplasmic complex and MK2 phosphorylates mouse RIPK1 at Ser321/336 in response to pro-inflammatory stimuli, such as TNF and LPS, and infection with the pathogen Yersinia enterocolitica. MK2 phosphorylation inhibits RIPK1 autophosphorylation, curtails RIPK1 integration into cytoplasmic cytotoxic complexes, and suppresses RIPK1-dependent apoptosis and necroptosis. In Yersinia-infected macrophages, RIPK1 phosphorylation by MK2 protects against infection-induced apoptosis, a process targeted by Yersinia outer protein P (YopP). YopP suppresses p38 /MK2 activation to increase Yersinia-driven apoptosis. Hence, MK2 phosphorylation of RIPK1 is a crucial checkpoint for cell fate in inflammation and infection that determines the outcome of bacteria-host cell interaction.

Yersinia (Y.) enterocolitica, an etiological agent of yersiniosis, is a bacterium whose pathogenicity is determined, among other things, by its ability to produce toxins. The aim of this article was to present the most important toxins that are produced by biotype 1A strains of Y. enterocolitica, and to discuss their role in the pathogenesis of yersiniosis. Y. enterocolitica biotype 1A strains are able to synthesize variants of thermostable YST enterotoxin and play a key role in the pathogenesis of yersiniosis. Biotype 1A strains of Y. enterocolitica also produce Y. enterocolitica pore-forming toxins, YaxA and YaxB. These toxins form pores in the cell membrane of host target cells and cause osmotic lysis, which is of particular importance in systemic infections. Insecticidal toxin complex genes have been detected in some clinical biotype 1A strains of Y. enterocolitica. However, their role has not yet been fully elucidated. Strains belonging to biotype 1A have long been considered non-pathogenic. This view is beginning to change due to the emerging knowledge about the toxigenic potential of these bacteria and their ability to overcome the defense barriers of the host organism.

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

Free-living amoebae (FLA) are widespread protozoa that can host bacterial pathogens, promoting their persistence in the environment. , a foodborne zoonotic pathogen, has been detected within amoebae, but its intracellular dynamics remain unclear. In this study, we explored the interaction between three strains-differing in biotype and virulence gene profile-and two spp.-a reference strain and a wild environmental isolate. All strains were internalized and survived up to 8 days in the collection strain and 16 days in the wild isolate. Intracellular persistence did not affect amoebal integrity or bacterial virulence profiles. Whole genome sequencing (WGS) revealed high genomic stability across strains, though specific mutations-such as in the gene, involved in stress response-emerged after persistence in the collection strain. These findings suggest that spp. not only shields from environmental stress but may also influence its genome and adaptive potential. This work expands the current understanding of biology and highlights the role of FLA as reservoirs and potential drivers of bacterial evolution. Their contribution to the bacteria persistence and gene exchange warrants further investigation, particularly in the context of antimicrobial resistance and food safety.

Bacterial bloodstream infections (BSI) are a major health concern and can cause up to 40% mortality. Pseudomonas aeruginosa BSI is often of nosocomial origin and is associated with a particularly poor prognosis. The mechanism of bacterial persistence in blood is still largely unknown. Here, we analyzed the behavior of a cohort of clinical and laboratory Pseudomonas aeruginosa strains in human blood. In this specific environment, complement was the main defensive mechanism, acting either by direct bacterial lysis or by opsonophagocytosis, which required recognition by immune cells. We found highly variable survival rates for different strains in blood, whatever their origin, serotype, or the nature of their secreted toxins (ExoS, ExoU or ExlA) and despite their detection by immune cells. We identified and characterized a complement-tolerant subpopulation of bacterial cells that we named “evaders”. Evaders shared some features with bacterial persisters, which tolerate antibiotic treatment. Notably, in bi-phasic killing curves, the evaders represented 0.1–0.001% of the initial bacterial load and displayed transient tolerance. However, the evaders are not dormant and require active metabolism to persist in blood. We detected the evaders for five other major human pathogens: Acinetobacter baumannii , Burkholderia multivorans , enteroaggregative Escherichia coli , Klebsiella pneumoniae , and Yersinia enterocolitica . Thus, the evaders could allow the pathogen to persist within the bloodstream, and may be the cause of fatal bacteremia or dissemination, in particular in the absence of effective antibiotic treatments.

Defining the Rcs (Regulator of Capsule Synthesis) regulon in Enterobacteriaceae has been the major focus of several recent studies. The overall role of the Rcs system in Yersinia enterocolitica is largely unknown. Our previous study showed that RcsB inhibits motility, biofilm formation and c-di-GMP production by negatively regulating flhDC, hmsHFRS and hmsT expression. To identify other cellular functions regulated by the RcsB, gene expression profiles of the wild type and ΔrcsB mutant were compared by RNA-Seq in this study. A total of 132 differentially expressed genes regulated by the RcsB have been identified, of which 114 were upregulated and 18 were downregulated. Further, the results of RNA sequencing were discussed with a focus on the predictive roles of RcsB in the inhibition of bacterial chemotaxis, flagellar assembly and infection. To confirm these predictions, we experimentally verified that the ΔrcsB mutant activated chemotactic behavior and flagella biosynthesis, and exhibited enhanced adhesion and invasion of Y. enterocolitica to Caco-2 cells. Although RcsB largely inhibits these physiological activities, the presence of RcsB is still of great significance for optimizing the survival of Y. enterocolitica as evidenced by our previous report that RcsB confers some level of resistance to the cationic antimicrobial peptide polymyxin B in Y. enterocolitica. Overall, the information provided in this study complements our understanding of Rcs phosphorelay in the regulation of Y. enterocolitica pathogenicity, and, simultaneously, provides clues to additional roles of the Rcs system in other members of family Enterobacteriaceae.

Yersiniosis is a common zoonotic enteric disease among humans, which has been linked to pigs and contaminated food, especially pork. The epidemiology of yersiniosis is still obscure, and studies on yersiniosis in pets are very scarce. In this study, we performed pheno- and genotypic characterisation of 50 Yersinia strains isolated from pets in Finland between 2012 and 2023. Y. enterocolitica 4/O:3/ST135, the most common type in human yersiniosis, was also the most common type (68%) found in clinical faecal samples in our study. Also, human pathogenic Y. enterocolitica 2/O:9/ST139 and Y. pseudotuberculosis O:1/ST9 and O:1/ST42 strains carrying all essential pathogenic genes were identified. Three Y. enterocolitica 4/O:3/ST9 strains were multi-drug-resistant and two of them were highly related, showing one allelic difference (AD) with core genome multi-locus sequence typing. Non-pathogenic, genotypically highly diverse Y. enterocolitica 1A strains, showing more than 1000 ADs and missing the essential virulence genes, were also recognised in dogs and cats. Our study demonstrates that pets can excrete human pathogenic Yersinia in their faeces and may serve as an infection source for human yersiniosis, especially in families with small children in close contact with their pets.