Virulence Factor Identification in the Banana Pathogen Dickeya zeae MS2.

The phytopathogen Dickeya zeae MS2 is a particularly virulent agent of banana soft rot disease. To begin to understand this banana disease and to understand the role of quorum sensing and quorum-sensing-related regulatory elements in D. zeae MS2, we sequenced its genome and queried the sequence for genes encoding LuxR homologs. We identified a canonical LuxR-LuxI homolog pair similar to those in other members of the genus Dickeya The quorum-sensing signal for this pair was N-3-oxo-hexanoyl-homoserine lactone, and the circuit affected motility, cell clumping, and production of the pigment indigoidine, but it did not affect infections of banana seedlings in our experiments. We also identified a luxR homolog linked to a gene annotated as encoding a proline iminopeptidase. Similar linked pairs have been associated with virulence in other plant pathogens. We show that mutants with deletions in the proline iminopeptidase gene are attenuated for virulence. Surprisingly, a mutant with a deletion in the gene encoding the LuxR homolog shows normal virulence.IMPORTANCEDickeya zeae is an emerging banana soft rot pathogen in China. We used genome sequencing and annotation to create an inventory of potential virulence factors and virulence gene regulators encoded in Dickeya zeae MS2, a particularly virulent strain. We created mutations in several genes and tested these mutants in a banana seedling infection model. A strain with a mutated proline iminopeptidase gene, homologs of which are important for disease in the Xanthomonas species phytopathogens, was attenuated for soft rot symptoms in our model. Understanding how the proline iminopeptidase functions as a virulence factor may lead to insights about how to control the disease, and it is of general importance as homologs of the proline iminopeptidase occur in dozens of plant-associated bacteria.

Dickeya zeae strains isolated from rice, banana and clivia rot plants show great virulence differentials.

BACKGROUND: Dickeya zeae is the causal agent of maize and rice foot rot diseases, but recently it was also found to infect banana and cause severe losses in China. Strains from different sources showed significant diversity in nature, implying complicated evolution history and pathogenic mechanisms. RESULTS: D. zeae strains were isolated from soft rot banana plants and ornamental monocotyledonous Clivia miniata. Compared with D. zeae strain EC1 isolated from rice, clivia isolates did not show any antimicrobial activity, produced less extracellular enzymes, had a much narrow host ranges, but released higher amount of extracellular polysaccharides (EPS). In contrast, the banana isolates in general produced more extracellular enzymes and EPS than strain EC1. Furthermore, we provided evidence that the banana D. zeae isolate MS2 produces a new antibiotic/phytotoxin(s), which differs from the zeamine toxins produced by rice pathogen D. zeae strain EC1 genetically and in its antimicrobial potency. CONCLUSIONS: The findings from this study expanded the natural host range of D. zeae and highlighted the genetic and phenotypic divergence of D. zeae strains. Conclusions can be drawn from a series of tests that at least two types of D. zeae strains could cause the soft rot disease of banana, with one producing antimicrobial compound while the other producing none, and the D. zeae clivia strains could only infect monocot hosts. D. zeae strains isolated from different sources have diverse virulence characteristics.

STAC3 as a poor prognostic biomarker in renal clear cell carcinoma: relationship with immune infiltration.

Calcium ions (Ca2+) are crucial in tumorigenesis and progression, with their elevated levels indicating a negative prognosis in Kidney Renal Clear Cell Carcinoma (KIRC). The influence of genes regulating calcium ions on the survival outcomes of KIRC patients and their interaction with the tumor's immune microenvironment is yet to be fully understood. This study analyzed gene expression data from KIRC tumor and adjacent non-tumor tissues using the TCGA-KIRC dataset to pinpoint genes that are differentially expressed in KIRC. Intersection of these genes with those regulating calcium ions highlighted specific calcium ion-regulating genes that exhibit differential expression in KIRC. Subsequently, prognostic risk models were developed using univariate Cox and LASSO-Cox regression analyses to verify their diagnostic precision. Additionally, the study investigated the correlation between tumor immunity and KIRC patient outcomes, assessing the contribution of STAC3 genes to tumor immunity. Further exploration entailed SSGASE, single-cell analysis, pseudotime analysis and both in vivo and in vitro experiments to evaluate STAC3's role in tumor immunity and progression. Notably, STAC3 was significantly overexpressed in tumor specimens and positively correlated with the degree of malignancy of KIRC, affecting patients' prognosis. Elevated STAC3 expression correlated with enhanced immune infiltration in KIRC tumors. Furthermore, silencing STAC3 curtailed KIRC cell proliferation, migration, invasion, and stemness properties. Experimental models in mice confirmed that STAC3 knockdown led to a reduction in tumor growth. Elevated STAC3 expression is intricately linked with immune infiltration in KIRC tumors, as well as with the aggressive biological behaviors of tumor cells, including their proliferation, migration, and invasion. Targeting STAC3 presents a promising strategy to augment the efficacy of current therapeutic approaches and to better the survival outcomes of patients with KIRC.

Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis.

PR domain-containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mechanisms. At first, peripheral blood-derived monocytes from patients with acute gouty arthritis and healthy individuals were collected as experimental samples. Then, macrophages were induced from monocytes using phorbol myristate acetate (PMA). The expression patterns of PRDM1, sirtuin 2 (SIRT2), and NLR family, pyrin domain-containing 3 (NLRP3) were characterized by RT-qPCR and Western blot assay. PMA-induced macrophages were stimulated by monosodium urate (MSU) for in vitro experimentation. Meanwhile, a murine model of MSU-induced acute gouty arthritis was established for in vivo validation. PRDM1 was highly expressed while SIRT2 poorly expressed in patients with acute gouty arthritis. Loss of PRDM1 could reduce NLRP3 inflammasome and mature IL-1ß levels and downregulate inflammatory cytokines in macrophages, which contributed to protection against acute gouty arthritis. Furthermore, results showed that PRDM1 could inhibit SIRT2 expression via binding to the deacetylase SIRT2 promoter. Finally, the in vivo experiments demonstrated that PRDM1 increased NLRP3 inflammasome and mature IL-1ß through transcriptional inhibition of SIRT2, whereby aggravating MSU-induced acute gouty arthritis. To sum up, PRDM1 increased NLRP3 inflammasome through inhibiting SIRT2, consequently aggravating MSU-induced acute gouty arthritis.