Biochemistry Assistant Professor Ophelia Venturelli has been awarded an Exploratory/ Developmental Research Grant (R21) by the National Institutes of Health (NIH). The award is in support of the development of new methods to uncover associations between antibiotic resistance genes and microbial hosts in the human gut microbiome.
The rise and spread of bacteria that are resistant to antibiotics is a growing global health crisis. Antibiotic resistant strains can harbor multiple antibiotic resistance genes (ARGs), which in turn can confer resistance to multiple antibiotics. This increasing resistance creates a major challenge in combating infectious diseases
Many ARGs are harbored on mobile genetic elements in different members of the microbiome, such as plasmids or bacteriophage elements. These genetic elements can move around the genome and between organisms that occupy a shared environment, enabling the transfer of ARGs.
“Mobile genetic elements are the vehicles that carry these genes around,” said Freeman Lan, postdoc in the Venturelli lab and the project lead. “If microbes are individual islands, MGEs are boats that travel between microbes and carry these genes around, allowing for HGT.”
HGT, or horizontal gene transfer, is the transfer of genes – such as drug resistance genes – from one species of microbe to another. It is a key process in the dissemination of drug resistant bacteria.
The human gut microbiome in particular is a dense and diverse ecosystem ideal for the transfer of ARGs. It is particularly vulnerable to ARG transfer following antibiotic exposure, when it may take months for the gut return to its initial state, or fail to ever fully recover.
But there’s a critical knowledge gap when it comes to understanding the ecological and evolutionary mechanisms that drive the reshuffling of ARGs in a complex microbial community like the human gut.
“It is suspected that HGT occurs a lot in the gut,” said Lan, “but it has been difficult to study directly, which is what our proposal is trying to address.”
The Venturelli lab proposes to address that knowledge gap by developing a groundbreaking new method to decipher the HGT network of a microbiome.
The method will use techniques from droplet microfluidics coupled with next generation sequencing. Droplet microfluidics involves conducting millions of individual reactions in tiny reactors, reactors that can’t be seen with the naked eye. Researchers can encapsulate single cells in these tiny reactors, and probe them for the existence of genes of interest, such as drug resistance genes.
“This technology,” said Venturelli, “will allow us to track antibiotic resistance genes in single cells, link the presence of these genes with the identity of the organism, and thus enable detection of horizontal gene transfer between species in the gut microbiome.”
The Venturelli lab is also applying the method in a collaboration with the Landick lab to determine how virulence genes – genes that allow a bacteria to cause disease – are regulated.
The R21 grant through the NIH is intended to encourage exploratory/developmental research by providing support for the early and conceptual stages of project development. The award provides nearly $200,000 over two years.