Researchers discover how bacteria adapt to new environment

It is a known fact that bacteria are extremely resourceful when it comes to adapting to a given environment. Now, a team of researchers have discovered a new trick that bacteria use: a kind of sponge that absorbs certain messengers.

The study was recently published in the journal 'Molecular Cell'.

The study was the subject of research at the Institute for Molecular Infection Biology (IMIB) of the University of Wurzburg and at the Helmholtz Institute for RNA-based Infection Research. Researchers in the laboratory of Professor Jorg Vogel, who held the Chair of Molecular Infection Biology I at JMU and Managing Director of the HIRI, figured out new details of these signalling pathways and mechanisms.

An earlier study in 'The Lancet', revealed that each year, at least 1.27 million people died from an infection with bacteria that are resistant to standard antibiotics. The authors feared that this number could rise to as many as ten million people by 2050.

This made the hunt for new substances, that are effective against resistant bacterial strains more urgent than ever. A potential approach focused on programmable RNA-based antibiotics. However, this required an in-depth understanding of the key RNA-based signalling pathways and mechanisms during an infection.

Gianluca Matera, a Ph.D. student at the IMIB, provided more information on the background of the paper he co-authored with Jorg Vogel. He said, "A lot of bacteria, such as Escherichia coli and Salmonella enterica, have a cell envelope consisting of an outer and an inner membrane. The main function of this envelope is to shield the bacteria from their environment but it also has to be permeable for nutrients which the bacteria need to thrive."

Numerous RNA entities interact in order to manage which substances can pass through the cell envelope and which are blocked at a given time, the latter allowing the bacteria to protect themselves against antibiotics, for example. The researchers have now identified a previously unknown protagonist in the bacterium Salmonella enterica: an "RNA sponge."

Such sponges belong to the class of "small RNAs." The Wurzburg study showed that the RNA sponge OppX mimicked the actual binding target of a special sRNA, the so-called MicF sRNA, in the bacterial outer membrane, intercepting it before it reaches its destination. Or in other words, it absorbed it like a sponge.

The MicF sRNA played a crucial role in the processes of the bacterial envelope. "The outer and inner membrane of the bacterial envelope cannot work independently from one another. So there have to be mechanisms that enable them to communicate with each other. Small non-coding RNAs, such as MicF, are one class of such regulators," Gianluca Matera explained.

Using a new technique developed at the Hebrew University of Jerusalem, the junior scientist identified the interacting partners of all these sRNAs in Salmonella -- comprehensively and in a single step.

The researchers described the effect of this interception process in detail: "Normally, OppX increases membrane permeability by boosting the expression of one of the main pores in the bacterial outer membrane," Matera specified. This scientific name of this pore is OmpF.

If the bacterium lacks the OppX sponge, its growth will be restricted, especially in a nutrient-poor environment. If, however, sufficient amounts of OppX are available, the OmpF pores in the membrane also become more active, increasing the uptake of nutrients if they are scarce.

The OmpF pores also assume a key function when the bacteria are attacked by antibiotics: The substances use them as their main points of entry into the cell. "Indirectly, OppX could have an impact on antibiotic efficacy by boosting OmpF production and thus the uptake of the antibiotic itself," Matera said.

OppX is the first known regulator of MicF activity -- the recently published data even supports the assumption that OppX is the most important, if not the only, sponge for the MicF sRNA. Therefore, knowing it is crucial to fully understand the cellular activity of MicF according to the authors of the study.

These new findings have been based on studies of bacteria grown in vitro under laboratory conditions. The scientists believed that the next challenge will be to extend these studies to more "realistic" conditions.

The first step in this direction had already been taken: "We are currently decoding the RNA interactome of Salmonella in infected host cells," Jorg Vogel explained. "Antibiotic resistance is one of the major health threats of our time -- that's why our basic research strives to contribute to the development of new therapeutics."

( With inputs from ANI )

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