Duval, E. | bioRxiv Science

bioRxiv2024

When does a parasite become a disease? eDNA unravels complex host-pathogen dynamics across environmental stress gradients in wild salmonid populations

Infectious diseases stem from disrupted interactions among hosts, parasites, and the environment. Both abiotic and biotic factors can influence infection outcomes by shaping the abundance of a parasites infective stages, as well as the hosts ability to fight infection. However, disentangling these mechanisms within natural ecosystems remains challenging. Here, combining environmental DNA analysis and niche modeling at a regional scale, we uncovered the biotic and abiotic drivers of a lethal infectious disease of salmonid fish, triggered by the parasite Tetracapsuloides bryosalmonae. We found that the occurrence and abundance of the parasite in the water--i.e., the propagule pressure-- were mainly correlated to the abundances of its two primary hosts, the bryozoan Fredericella sultana and the fish Salmo trutta, but poorly to local abiotic environmental stressors. In contrast, the occurrence and abundance of parasites within fish hosts--i.e., proxies for disease emergence--were closely linked to environmental stressors (water temperature, agricultural activities, dams), and to a lesser extent to parasite propagule pressure. These results suggest that pathogen distribution alone cannot predict the risk of disease in wildlife, and that local anthropogenic stressors may play a pivotal role in disease emergence among wild host populations, likely by compromising the hosts ability to fight the parasite. Our study sheds light on the intricate interplay between biotic and abiotic factors in shaping pathogen distribution and raises concerns about the effects of global change on disease emergence.

ecology↗

bioRxiv2022

Putative SET-domain methyltransferases in Cryptosporidium parvum and histone methylation during infection

Cryptosporidium parvum is a major cause of an intestinal pathology called cryptosporidiosis which affects humans and other vertebrates. Despite being declared as a public health problem by World Health Organization (WHO) since 2006, pathogenesis caused by this parasite remains poorly understood. More recently, C. parvum has been linked with oncogenesis. In particular, the mechanisms involved in the processes of gene expression regulation are completely unexplored in Cryptosporidium. In the current study, we took the opportunity to investigate a dynamic epigenetic modification called histone lysine methylation during the life cycle of the parasite. We successfully identified putative SET-domain containing proteins, lysine methyltransferases (KMTs), which catalyze the methylation of different lysine residues. Phylogenetic analysis classified them into distinct subfamilies namely CpSET1, CpSET2, CpSET8, CpKMTox and CpAKMT. Structural analysis further characterized CpSET1, CpSET2 and CpSET8 to be histone lysine methyltransferases (HKMTs). Their functional significance was predicted by using site-specific methyl-lysine antibodies during development of the parasite (CpSET1:H3K4; CpSET2:H3K36; CpSET8:H4K20). In particular, the SET domain of CpSET8 showcased methyltransferase activity confirming the existence of functional HKMTs in Cryptosporidium. Moreover, the consequence of C. parvum infection on the host lysine methylation events highlights the inherit potential of the parasite to exploit the host epigenetic regulation to its advantage. Thus, this study is the first one to provide insights on epigenetics mechanisms occurring throughout the parasites life cycle and during the interaction with its host. As Cryptosporidium is a protozoan that significantly affects the health of both humans and animals, a better understanding of its developmental processes within the definitive host may highlight novel infection control strategies. Author SummaryCryptosporidium species have a very compact genome (~9.2 Mb) unlike its apicomplexan homologs such as Toxoplasma (~63 Mb). Moreover, the lack of large families of transcriptional factors requires them to heavily rely on chromatin remodeling components for its gene regulation. Thus, study and identification of novel elements which contribute to chromatin dynamics could assist a better understanding of the biology of this parasite. In the current study we investigated histone lysine methylation, a dynamic epigenetic modification which regulates gene activation as well as repression. More importantly, characterizing the enzymes which bring about this regulation, provides potential new druggable targets to attack the parasite.

microbiology↗