Navigation Links
Scientists identify proteins that help bacteria put up a fight

COLUMBUS, Ohio Scientists have identified the role of two proteins that contribute to disease-causing bacteria cells versatility in resisting certain classes of antibiotics.

The finding is a step toward development of drug therapies that could target bacterial resistance at its cellular source. Before researchers can design such drugs, they must understand all of the activities at play in the conflict between bacteria and the agents that kill them.

This finding by Ohio State University microbiologists extends the understanding of how bacteria cells resist antibiotics through the activities of two genetically distinct forms of what are called MprFs, or multiple peptide resistance factors. The proteins they studied are MprF1 and MprF2.

These proteins were found to be key to the mechanism allowing bacteria cells to change the electrical charge of their membrane, which is how the cells develop their resistance to certain antimicrobial agents and, more generally, how they adapt their membrane to new environmental conditions, such as those provided by their host organism.

Both of these proteins are potentially very good drug targets because in theory, if you can target them and inhibit their action, you can make bacteria strains more susceptible to existing antibiotics, said Michael Ibba, associate professor of microbiology at Ohio State and a coauthor of the study.

The findings are described online in this weeks issue of Proceedings of the National Academy of Sciences.

Scientists have already observed that the cell membranes of many disease-causing bacteria develop resistance by changing their electrical charge from negative to positive. Many antibiotics work because they carry a positive charge that attracts them to negatively charged bacteria cells. The opposite charges allow antibiotics to penetrate and kill bacteria. But by changing their naturally occurring negative charge to positive, some bacteria cells establish a protective coat that repels the antibiotic.

A common example of antibiotic resistance is Methicillin-resistant Staphylococcus aureus (MRSA), the strain of bacteria responsible for thousands of difficult-to-treat infections reported in humans each year.

There is a dispute that remains unresolved as to whether or not this pathway were investigating is involved in MRSA. Its very unclear. By understanding the mechanism, we might be able to find out if this is involved in MRSA or not, Ibba said.

Ibba and Herv Roy, a postdoctoral researcher at Ohio State and lead author of the study, concentrated on exploring the activities of these specific MprF proteins, which are just two of dozens of forms of a class of genes associated with the development of resistance in about 200 bacteria species. They investigated the activity of two forms of MprF from the pathogen Clostridium perfringens, one of the most common sources of food poisoning in the United States.

MprF proteins affect the membranes charge by using an adapter molecule, called transfer RNA (tRNA), to transfer amino acids to the lipids that make up the cell membrane. This action leads to modification of the membrane and the change in its charge.

Ibba and Roy found that both MprF1 and MprF2 perform this same function, but they use different amino acids that lead to the modification. The amino acid lysine has already been identified as a player in this modification, and is used by MprF2. Ibba and Roy found that MprF1, however, uses the amino acid alanine instead. This amino acid also contributes to cell membrane modification and seems to have additional functions that remain unknown.

This is a new function that we discovered, that MprF1 uses alanine, which then allows the cell to fine tune the properties of the membrane, Roy said. Earlier studies found these effects on the membrane, but no one knew what protein caused it.

What makes these proteins even more potent in the resistance effort is that they can use the adapter molecule in a variety of forms to achieve membrane modification. When the researchers manipulated the tRNAs structure and properties to match differences in the molecule that would occur in different species of bacteria, the proteins could still recognize the molecule and put it to use to perform the amino acid transfer that changes the cell membrane.

This means that there is no species barrier for the spread of this virulence factor among other bacteria because this protein can recognize tRNA in any species, no matter what it looks like, Roy said.

Ibba and Roy describe their findings as only the beginning of investigating the role of the MprF family of proteins in bacteria. They believe other amino acids could also be used that would modify bacteria cell membranes, and are investigating additional pathways within the cells that lead to remodeled membranes.

We know the change to the membrane is key to resistance, Ibba said. We now know there is not just one way that can happen. We have just found a second way an organism can do this, and it is able to make the change to the membrane in two different ways. From our findings there are almost certainly even more ways that the membrane can be modified, and thats what were looking for next.


Contact: Michael Ibba
Ohio State University

Related medicine news :

1. CSHL scientists discover new details of a gene-regulatory network governing metabolism
2. Scientists make first map of emerging-disease hotpsots
3. Scientists shed light on long-distance signaling in developing neurons
4. Scientists explore consciousness
5. Scientists using laser light to detect potential diseases via breath samples, says new study
6. Scientists move towards stem cell therapy trials to mend shattered bones
7. U-M scientists develop tool to probe role of oxidative stress in aging, disease
8. Scientists Show Stem Cells Dont Cause Cancer
9. Microbial cheaters help scientists ID social genes
10. Scientists solve structure of gene regulator that plays key role in cancer
11. VEGF Neutralization Can Damage Brain Vessels, Say Schepens Eye Research Institute Scientists
Post Your Comments:
(Date:11/26/2015)... ... November 26, 2015 , ... Patients at Serenity ... have come together on Thanksgiving Day to share the things that they are ... the Serenity Point YouTube channel, patients displayed what they wrote on index cards, ...
(Date:11/26/2015)... (PRWEB) , ... November 26, 2015 , ... ... a real-time eReferral system for diagnostic imaging in the Waterloo region. Using the ... and Nuclear Medicine tests directly from their electronic medical record (EMR) without the ...
(Date:11/26/2015)... ... , ... The Catalent Applied Drug Delivery Institute today announced ... form selection in early phase drug development. The first of these is to ... the UK’s emerging life sciences companies, corporate partners, and investors, at Milton Park, ...
(Date:11/26/2015)... ... November 26, 2015 , ... PRMA Plastic Surgery is updating their record books ... their 6,000th free flap breast reconstruction surgery! , “What an accomplishment for the PRMA ... rebuild lives and it’s an honor to have served all of these women.” , ...
(Date:11/26/2015)... ... 26, 2015 , ... Pixel Film Studios brings Final Cut ... Vintage. This newly styled ProTrailer pack comes with 30 all-new vintage-inspired designs, with ... users limitless opportunities to stylize and create designs quickly and easily, all within ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... , November 26, 2015 ... the "Self Administration of High Viscosity Drugs" ... ) has announced the addition of the ... report to their offering. --> Research ... addition of the "Self Administration of High ...
(Date:11/25/2015)... , Nov. 26, 2015  The total global healthcare industry ... over 2015-2016. Latin America has the ... , (excluding Japan ), is second with ... continues to face increased healthcare expenditure. In 2013-2014, total government ... from 43.5% in 2008-2009 to 41.2% in 2013-2014. In real ...
(Date:11/25/2015)... , Nov. 25, 2015 On Tuesday, ... federal bellwether trial against Wright Medical Technology, Inc. ... their Conserve metal-on-metal hip implant device, awarded $11 ... a two week trial and three days of ... hip device was defectively designed and unreasonably dangerous, ...
Breaking Medicine Technology: