Hypoxia-induced HIF-1α promotes Listeria monocytogenes invasion into tilapia.

ABSTRACT

HIF-1α is a nuclear transcription factor, and its activity is tightly regulated by the level of available oxygen in cells. Here, we investigated the roles of HIF-1α in the invasion of Listeria monocytogenes into tilapia under hypoxic environments. We found that the expression levels of HIF-1α in examined tissues of hypoxic tilapia were significantly upregulated, indicating that the tissue cells have been in hypoxic conditions. After 24-h infection with L. monocytogenes, we found that bacterial burden counts increased significantly in all examined tissues of hypoxic fish. To explore why the bacterial count increased significantly in the tissues of hypoxic fish, we modulated HIF-1α expression through RNAi technology. The results indicated that c-Met expression levels were positively related to HIF-1α expression. Since c-Met is the receptor of InlB that plays critical roles in the adhesion and invasion of L. monocytogenes, the ∆InlB strain was used to further explore the reason for the significant increase in bacterial counts in hypoxic fish. As expected, the decrease in the adhesion ability of ∆InlB suggested that InlB mediates L. monocytogenes infection in tilapia. After being infected with ∆InlB strain, we found that the bacterial counts in hypoxic fish were not affected by hypoxic conditions or HIF-1α expression levels. These findings indicate that HIF-1α may promote the internalization of InlB by upregulating c-Met expression and therefore contributes to the invasion of L. monocytogenes into hypoxic tilapia. IMPORTANCE Listeria monocytogenes is a zoonotic food-borne bacterial pathogen with a solid pathogenicity for humans. After ingestion of highly contaminated food, L. monocytogenes is able to cross the intestine invading phagocytic and nonphagocytic cells and causes listeriosis. China is the world's largest supplier of tilapia. The contamination rate of L. monocytogenes to tilapia products was as high as 2.81%, causing a severe threat to public health. This study revealed the underlying regulatory mechanisms of HIF-1α in the invasion of L. monocytogenes into tilapia under hypoxic environments. This study will be helpful for better understanding the molecular mechanisms of hypoxic environments in L. monocytogenes infection to tilapia. More importantly, our data will provide novel insights into the prevention and control of this pathogen in aquaculture.