evaluating-virulence-pathogenesis-aeromonas-infection-caenorhabditis

Evaluating Virulence and Pathogenesis of <em>Aeromonas</em> Infection in a <em>Caenorhabditis elegans</em> Model

The human pathogen Aeromonas has been clinically shown to cause gastroenteritis, wound infections, septicemia, and urinary tract infections. Most human ...

National Cheng Kung University

Stress-related mucosal disease (SRMD) causes considerable morbidity and mortality in critically ill patients. 3,4-Methylenedioxyphenol (sesamol) has been reported to have potent antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of sesamol on water immersion restraint- (WIR-) induced SRMD in rats. Rat gastric ulcer and hemorrhage were induced by WIR. Rats were pretreated orally with various doses of sesamol (0.1, 0.3, and 1 mg/kg, resp.) 30 min before WIR. Gastric mucosal ulceration, hemoglobin, lipid peroxidation, mucus secretion, proinflammatory cytokines, and nuclear factor (NF)-κB levels were determined 4 h after WIR. In addition, the infiltration of neutrophil and macrophage into gastric mucosa was also determined after WIR. Water immersion restraint increased gastric mucosal ulcer and hemorrhage, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels but failed to affect mucosal lipid peroxidation and mucus secretion compared with non-WIR. Sesamol significantly decreased gastric ulceration and hemorrhage and inhibited mucosal TNF-α, IL-1β, and IL-6 production and NF-κB activity in WIR-treated rats. In addition, increased myeloperoxidase and CD68 levels in gastric mucosa were found in WIR-treated rats compared to non-WIR rats. Sesamol did not affect myeloperoxidase but decreased CD68 levels in mucosa in WIR-treated rats. Sesamol may protect against SRMD by inhibiting gastric mucosal proinflammatory cytokines in rats.

Protective effect of 3,4-methylenedioxyphenol (sesamol) on stress-related mucosal disease in rats.

The emergence of MRSA strains resistant to most antibiotics is a serious threat to public health. Based on our discovery that the tyrosine kinase inhibitor sorafenib exhibits inhibitory activity against Staphylococcus species, the objective of this study is to exploit this unique antibacterial activity of sorafenib to develop novel antibacterial agents against MRSA.

In vitro and in vivo activity of a novel sorafenib derivative SC5005 against MRSA.

A variety of bacterial infections cause muscle necrosis in humans.has epidermis and bands of muscle that resemble soft-tissue structures in mammals and humans. Here, we developed a muscle necrosis model caused byinfection in. Our data showed thatinfected and killedrapidly. Characteristic muscle damage ininduced bywas demonstrated. Relative expression levels of host necrosis-associated genes,,, andincreased significantly afterinfection. The RNAi sensitive NL2099) worms with knockdown of necrosis genes ofandby RNAi showed prolonged survival afterinfection. Specifically knockdown ofandby RNAi in WM118 worms, which restricted RNAi only to the muscle cells, conferred significant resistance toinfection. In contrast, the severity of muscle damage and toxicity produced by thehemolysin-deletion mutant is attenuated. In another example, shiga-like toxin-producing enterohemorrhagic(EHEC) known to elicit toxicity towith concomitant enteropathogenicty, did not cause muscle necrosis asdid. Taken together, these results show thatinfection induces muscle necrosis and rapid death of infected, which are similar to muscle necrosis in humans, and then validate the value of themodel withinfection in studyingpathogenicity.

A Disease Model of Muscle Necrosis Caused byInfection in.

Musashi-1 (MSI1), one of the RNA-binding proteins, is abundantly found not only in neural stem cells but also in several cancer tissues and has been reported to act as a positive regulator of cancer progression. Growing evidence indicates that PKR and eIF2α play pivotal roles in the stimulation of stress granule formation as well as in the subsequent translation modulation in response to stressful conditions; however, little is known about whether MSI1 is involved in this PKR/eIF2α cancer stem cell-enhancing machinery. In this study, we demonstrated that MSI1 promotes human glioblastoma multiforme (GBM) stem cells and enhances chemoresistance when exposed to sublethal stress. The overexpression of MSI1 leads to a protective effect in mitigating drug-induced cell death, thus facilitating the formation of chemoresistant stress granules (SGs) in response to arsenic trioxide (ATO) treatment. SG components, such as PKR and eIF2α, were dominantly activated and assembled, while ATO was engaged. The activated PKR and eIF2α contribute to the downstream enhancement of stem cell genes, thereby promoting the progression of GBM. The silencing of MSI1 or PKR both obviously withdrew the phenomena. Taken together, our findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2α signalling cascade.

Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma.

Innate immunity is the primary defense mechanism against infection in metazoans. However, aberrant upregulation of innate immune-signaling pathways can also be detrimental to the host. The p38 MAPK/PMK-1 innate immune-signaling pathway has been demonstrated to play essential roles in cellular defenses against numerous infections in metazoans, including . However, the negative regulators that maintain the homeostasis of this important innate immune pathway remain largely understudied. By screening a focused RNAi library against the kinome of , we identified RIOK-1, a human RIO kinase homolog, as a novel suppressor of the p38 MAPK/PMK-1 signal pathway. We demonstrated that the suppression of  confers resistance to  infection in . Using quantitative real time-PCR and  reporter worms, we found the expression levels of  to be significantly upregulated in worms infected with . Our genetic epistasis analysis suggested that  acts on the upstream of the p38 MAPK/ genetic pathway. Moreover, the suppression of  enhanced the p38 MAPK signal, suggesting that  is a negative regulator of this innate pathway in . Our epistatic results put  downstream of , which encodes a p38 MAPK downstream transcription factor and serves as a feedback loop to the p38 MAPK pathway during an  infection. In conclusion,  is proposed as a novel innate immune suppressor and as a negative feedback loop model involving p38 MAPK, SKN-1, and RIOK-1 in .

Yi-Wei Chen

Institute of Basic Medical Sciences,
College of Medicine,
Institute of Basic Medical Sciences, College of Medicine

National Cheng Kung University

Evaluating Virulence and Pathogenesis of Aeromonas Infection in a Caenorhabditis elegans Model

Yi-Wei Chen

Institute of Basic Medical Sciences,College of Medicine,Institute of Basic Medical Sciences, College of Medicine

National Cheng Kung University

Evaluating Virulence and Pathogenesis of Aeromonas Infection in a Caenorhabditis elegans Model

Institute of Basic Medical Sciences,
College of Medicine,
Institute of Basic Medical Sciences, College of Medicine