Effects of dietary supplementation of three strains of Lactococcus lactis on HIFs genes family expression of the common carp following Aeromonas hydrophila infection

HIFs (Hypoxia inducible factors) are the main regulators of the expression change of oxygen-dependent genes, in addition, they also play important roles in immune regulation. HIFs participate in infectious diseases and inflammatory responses, providing us a new therapeutic target for the treatment of diseases. In this study, 16 HIFs were identified in common carp genome database. Comparative genomics analysis showed large expansion of HIF gene family and approved the four round whole genome duplication (WGD) event in common carp. To further understand the function of HIFs, the domain architectures were predicted. All HIF proteins had the conserved HLH-PAS domain, which were essential for them to form dimer and bind to the downstream targets. The differences in domain of HIF alpha and HIF beta might result in their different functions. Phylogenetic analysis revealed that all HIFs were divided into two subfamilies and the HIFs in common carp were clustered with their teleost counterparts indicating they are highly conservative during evolution. In addition, the tissue distribution was examined by RT-PCR showed that most of HIF genes had a wide range of tissue distribution but exhibited tissue-specific expression patterns. The expression divergences were observed between the copy genes, for example, HIF1A-1, HIF2A-1, ARNT-2 had wide tissue distribution while their copies had limited tissue distribution, proving the function divergence of copies post the WGD event. In order to find an effective activation of HIFs and apply to treatment of aquatic diseases, we investigate the dietary supplementation effects of different strains of Lactococcus laths on the expression of HIFa subfamily members in kidney of common carp infected with A. hydrophila. In addition, all of the HIF genes have a high expression in the early stages of infection, and decreased in the treatment time point of 48 h in common carp. This phenomenon confirms that as a switch, the main function of HIFs is to regulate the production of immune response factors in early infection. So activation of the switch may be an effective method for infectious disease treatment. As expected, the treatment groups improved the expression of HIFs compared with the control group, and the effects of the three strains are different. The strain1 of L. lactis had a stronger induction on HIF genes than strain2 and strain3, and it might be applied as a potential activation of HIF genes for disease treatment. So, adding befitting L. lactic maybe a well method to activate the HIF genes to protect them from mycobacterial infection.