Virulence最新文献

Candida albicans is an opportunistic fungal pathogen known for surviving in various nutrient-limited conditions within the host and causing infections. Our prior research revealed that Hfl1p, an archaeal histone-like or Hap5-like protein, is linked to mitochondrial ATP generation and yeast-hyphae morphogenesis. However, the specific roles of Hfl1p in these virulence behaviours, through its function in the CBF/NF-Y complex or as a DNA polymerase II subunit, remain unclear. This study explores Hfl1p's diverse functions in energy metabolism and morphogenesis. By combining proteomic analysis and phenotypic evaluations of the hfl1Δ/hfl1Δ mutant with ChIP data, we found that Hfl1p significantly impacts mitochondrial DNA-encoded CI subunits, the tricarboxylic acid (TCA) cycle, and morphogenetic pathways. This influence occurs either independently or alongside other transcription factors recognizing a conserved DNA motif (TAXXTAATTA). These findings emphasize Hfl1p's critical role in linking carbon metabolism and mitochondrial respiration to the yeast-to-filamentous form transition, enhancing our understanding of C. albicans' metabolic adaptability during morphological transition, an important pathogenic trait of this fungus. This could help identify therapeutic targets by disrupting the relationship between energy metabolism and cell morphology in C. albicans.

Anthracnose, caused by Colletotrichum species, induces significant economic damages to crop plants annually, especially for Camellia oleifera. During infection, the counter-defence mechanisms of plant pathogens against ROS-mediated resistance, however, remain poorly understood. By employing Weighted Gene Co-expression Network Analysis (WGCNA), we identified ACTIVATOR PROTEIN-1 (AP-1), a bZIP transcription factor, as significant to infection. And deletion of CfAP1 inhibited aerial hyphae formation and growth under oxidative stress. Furthermore, RNA-seq analysis post H₂O₂ treatment revealed 33 significantly down-regulated genes in the AP-1 deficient strain, including A12032, a dual specificity phosphatase (DSP) homologous to MSG5 from Saccharomyces cerevisiae. This ΔCfmsg5 strain showed enhanced oxidative tolerance, reduced ROS scavenging, and negative regulation of the CWI MAPK cascade under oxygen stress, suggesting its involvement in oxidative signal transduction. Importantly, we provide evidence that CfMsg5 regulates growth, endoplasmic reticulum stress, and several unfolded protein response genes upregulated in ΔCfmsg5. Collectively, this study identified core components during C. fructicola infection and highlights a potential regulatory module involving CfAp1 and CfMsg5 in response to host ROS bursts. It provides new insights into fungal infection mechanisms and potential targets like CfAP1 and CfMSG5 for managing anthracnose diseases.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global swine industry. The emergence of new, highly virulent strains has precipitated recurrent outbreaks worldwide, underscoring the ongoing battle between host and virus. Thus, there is an imperative to formulate a more comprehensive and effective disease control strategy. Studies have shown that host non-coding RNA (ncRNA) is an important regulator of host - virus interactions in PRRSV infection. Hence, a thorough comprehension of the roles played by ncRNAs in PRRSV infection can augment our understanding of the pathogenic mechanisms underlying PRRSV infection. This review focuses on elucidating contemporary insights into the roles of host microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in PRRSV infection, providing both theoretical foundations and fresh perspectives for ongoing research into the mechanisms driving PRRSV infection and its pathogenesis.

Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.

A variety of animals can be infected by encephalomyocarditis virus (EMCV). EMCV is the established causative agent of myocarditis and encephalitis in some animals. EMCV causes high fatality in suckling and weaning piglets, making pigs the most susceptible domestic animal species. Importantly, EMCV has zoonotic potential to infect the human population. The ability of the pathogen to avoid and undermine the initial defence mechanism of the host contributes to its virulence and pathogenicity. A large body of literature highlights the intricate strategies employed by EMCV to escape the innate immune machinery to suit its "pathogenic needs." Here, we also provide examples on how EMCV interacts with certain host proteins to dampen the infection process. Hence, this concise review aims to summarize these findings in a compendium of decades of research on this exciting yet underappreciated topic.

African swine fever (ASF) is a rapidly fatal viral haemorrhagic fever in Chinese domestic pigs. Although very high mortality is observed in pig farms after an ASF outbreak, clinically healthy and antibody-positive pigs are found in those farms, and viral detection is rare from these pigs. The ability of pigs to resist ASF viral infection may be modulated by host genetic variations. However, the genetic basis of the resistance of domestic pigs against ASF remains unclear. We generated a comprehensive set of structural variations (SVs) in a Chinese indigenous Xiang pig with ASF-resistant (Xiang-R) and ASF-susceptible (Xiang-S) phenotypes using whole-genome resequencing method. A total of 53,589 nonredundant SVs were identified, with an average of 25,656 SVs per individual in the Xiang pig genome, including insertion, deletion, inversion and duplication variations. The Xiang-R group harboured more SVs than the Xiang-S group. The F-statistics (F_ST) was carried out to reveal genetic differences between two populations using the resequencing data at each SV locus. We identified 2,414 population-stratified SVs and annotated 1,152 Ensembl genes (including 986 protein-coding genes), in which 1,326 SVs might disturb the structure and expression of the Ensembl genes. Those protein-coding genes were mainly enriched in the Wnt, Hippo, and calcium signalling pathways. Other important pathways associated with the ASF viral infection were also identified, such as the endocytosis, apoptosis, focal adhesion, Fc gamma R-mediated phagocytosis, junction, NOD-like receptor, PI3K-Akt, and c-type lectin receptor signalling pathways. Finally, we identified 135 candidate adaptive genes overlapping 166 SVs that were involved in the virus entry and virus-host cell interactions. The fact that some of population-stratified SVs regions detected as selective sweep signals gave another support for the genetic variations affecting pig resistance against ASF. The research indicates that SVs play an important role in the evolutionary processes of Xiang pig adaptation to ASF infection.

The incidence rate of pyogenic liver abscess caused by multidrug-resistant bacteria has increased in recent years. This study aimed to identify the clinical characteristics and risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. We conducted a retrospective analysis of the clinical features, laboratory test results, and causes of pyogenic liver abscesses in 239 patients admitted to a tertiary hospital. Multivariable logistic regression was used to identify risk factors for multidrug resistance. Among patients with pyogenic liver abscesses, the rate of infection caused by multidrug-resistant organisms was observed to be 23.0% (55/239), with a polymicrobial infection rate of 14.6% (35/239). Additionally, 71 cases (29.7%) were associated with biliary tract disease. Patients with pyogenic liver abscesses caused by multidrug-resistant organisms had a significantly higher likelihood of polymicrobial infection and increased mortality (7/44 [15.9%] vs. 3/131 [2.3%]; p = .003). The Charlson Comorbidity Index (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.06-1.68), hospitalization (aOR: 10.34, 95% CI: 1.86-60.3) or an invasive procedure (aOR: 9.62; 95% CI: 1.66-71.7) within the past 6 months, and gas in the liver on imaging (aOR: 26.0; 95% CI: 3.29-261.3) were independent risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. A nomogram was constructed based on the risk factors identified. The nomogram showed high diagnostic accuracy (specificity, 0.878; sensitivity 0.940). Multidrug-resistant organisms causing pyogenic liver abscesses have specific characteristics. Early identification of patients at high risk of infection with multidrug-resistant organisms could help improve their management and enable personalized treatment.

Tilapia Lake Virus (TiLV) is associated with pathological changes in the brain of infected fish, but the mechanisms driving the virus's neuropathogenesis remain poorly characterized. TiLV establishes a persistent infection in the brain of infected fish even when the virus is no longer detectable in the peripheral organs, rendering therapeutic interventions and disease management challenging. Moreover, the persistence of the virus in the brain may pose a risk for viral reinfection and spread and contribute to ongoing tissue damage and neuroinflammatory processes. In this review, we explore TiLV-associated neurological disease. We discuss the possible mechanism(s) used by TiLV to enter the central nervous system (CNS) and examine TiLV-induced neuroinflammation and brain immune responses. Lastly, we discuss future research questions and knowledge gaps to be addressed to significantly advance this field.