Researchers discover new bacterial mechanism for environmental adaptation

Bacteria can adapt to any environment with great skill. Wrzburg’s researchers discovered a new method bacteria use to absorb certain messengers.

According to a recent study in the journal, around 1.27 million people are killed each year by bacteria that is resistant standard antibiotics. The Lancet reveals. The authors fear that this number could increase to 10 million by 2050.

This makes it even more urgent to search for new drugs that are effective against resistant bacterial strains. One potential approach is to use programmable RNA based antibiotics. This requires a deep understanding of the key RNA signaling pathways and mechanisms that occur during an infection.

New signaling pathways identified

This is the focus of research at the Institute for Molecular Infection Biology at the University of Wrzburg as well as at the Helmholtz Institute for RNA based Infection Research. The laboratory of Professor Jrg Vogel (who holds the Chair in Molecular Infection Biology I at JMU) has discovered new details about these signaling pathways. The results of their study are presented in the latest issue. Molecular Cell.

Gianluca Matera, a PhD student at the IMIB provides more information about the background of the paper he coauthored with Jrg Vogel. He said: “Many bacteria, such as Salmonella enterica and Escherichiacoli, have a cell membrane that consists of an outer and inner membrane. This envelope serves two main purposes: to protect the bacteria from the environment and to allow them to access the nutrients they need to thrive.

A previously unknown player

Numerous RNA entities work together to control which substances are allowed to pass through the cell membrane and which are blocked at any given time. This allows the bacteria to defend themselves against antibiotics. Researchers have identified an unknown protagonist in Salmonella enterica’s bacterium: “RNA sponge.”

Such sponges belong in the class of “smallRNAs.” Wrzburg studies have shown that OppX, an RNA sponge, mimics the binding target for a special sRNA (the so-called MicF) in the bacterial membrane, intercepting it before reaching its destination. It absorbs it like an sponge.

Communication between the membranes

The MicF-sRNA plays an important role in the formation of the bacterial membrane. “The outer membrane and inner membranes of a bacterial envelope cannot function independently. There must be mechanisms that allow them to communicate with one another. Gianluca Mattera explains that MicF is one type of such regulators. Using a new technique developed at the Hebrew University of Jerusalem, the junior scientist has now identified the interacting partners of all these sRNAs in Salmonellacomprehensively and in a single step.

Researchers were able to describe the effects of this interception process in detail. Matera states that OppX is a method that increases membrane permeability by increasing the expression of one main pores in the bacterial membrane. OmpF is the scientific name for this pore.

The OppX sponge is essential for bacterium growth. This is especially true in nutrient-poor environments. However, if enough OppX is available, the OmpF pores within the membrane become more active and increase the uptake of nutrients.

Indirect impact on antibiotics

When antibiotics are applied to bacteria, OmpF pores serve a critical function. The substances use them for entry into cells. Matera states that OppX could indirectly have an effect on antibiotic efficacy by increasing OmpF production and therefore the uptake of antibiotics.

OppX, the first known regulator of MicF activitiy, has recently been published data that supports the hypothesis that OppX, if not the sole, sponge for the MicF’sRNA. According to the study’s authors, it is essential to understand the cellular activity and function of MicF.

These new findings are based upon studies of bacteria grown in vitro in laboratory conditions. Scientists believe the next challenge is to expand these studies to more realistic conditions. Jrg Vogel explains that the first step in this direction has already taken: “We are currently decoding and analyzing the RNA interactome for Salmonella in infected host cell.” “Antibiotic resistance is one the most serious health threats of our times. Our basic research aims to contribute to the development and application of new therapeutics.”