Hope to beat resistant bacteria

Behind the Headlines

Wednesday March 12 2008

Xray of pneumonia

X-ray of the chest of a patient with bacterial pneumonia (grainy white area, centre right) in the lower lobe of the left lung (black)

‘UK team in bacteria breakthrough’, the BBC News headline reads, reporting on the hope that scientists might be able to restore the full antibacterial properties of penicillin.

This follows research that identified how a type of bacteria that causes pneumonia becomes resistant to penicillin. The researchers have reportedly found that in penicillin-resistant bacteria, an enzyme (MurM) acts differently than in bacteria that are susceptible to such antibiotics. It is hoped that these findings may lead to the development of new drugs that will inhibit resistance to antibiotics by preventing certain chemical reactions of the enzyme.

Penicillin was the first antibiotic and the widespread use of it and similar drugs has led to a change in certain strains of bacteria that makes them resistant to its actions. Further research is needed to see whether this newly-identified protein is specific to the particular bacteria investigated and whether there is the potential for developing a new class of drug that targets the resistance mechanism discovered here. Ideally, this would lead to the production of an antibacterial that could be used against bacteria that have become resistant to regularly used antibiotics (e.g. MRSA), but whether this is possible remains to be seen.

Where did the story come from?

Adrian J. Lloyd and colleagues from the University of Warwick; Université Laval, Quebec, and The Rockerfeller University, New York carried out the research. The study was funded by the Wellcome Trust. The study was published in the peer-reviewed scientific journal: Journal of Biological Chemistry.

What kind of scientific study was this?

The widespread use of penicillin and other antibiotics over many years has led to certain strains of bacteria becoming resistant to their actions. One bacterium with strains that are antibiotic resistant, Streptococcus pneumoniae, causes pneumonia.

In this complex laboratory study, the researchers investigated the actions of a bacterial enzyme (MurM) on a molecule in the cell walls of the pneumococcal bacteria. The molecule, peptidoglycan, gives strength and rigidity to the cell. As it is the bacterial cell wall that is the target of traditional antibiotics, there is a theory that this enzyme could play a role in whether the bacteria is resistant to certain forms of antibiotic.

The researchers looked at the actions of MurM in two strains of Streptococcus pneumoniae bacteria, one that is highly resistant to penicillin (strain 159) and one that is susceptible (Pn16), to assess whether it caused any difference in the structure of the building blocks of the peptidoglycan in the cell walls.

The methods used were complex and are not discussed in detail here. The enzymes, cell walls, proteins, and relevant genes from the two different strains of bacteria, were synthesised and purified as appropriate. The researchers compared the molecular structures of the cell walls in the two strains and looked at how the enzyme MurM acted on their molecules.

What were the results of the study?

The researchers found that in the susceptible strain Pn16, the enzyme MurM added an amino acid called serine to the building blocks of the cell walls. In contrast, in the strain resistant to penicillin, strain 159, MurM added the amino acid alanine to the building blocks.

What interpretations did the researchers draw from these results?

The authors conclude that the MurM enzyme in the two bacterial strains that were tested is responsible for altering the chemical structure of peptidoglycan in the cell wall. They have also revealed many important features of the material involved in the binding reactions, and have an improved understanding of how the different amino acids bind to each other to form the molecule in the cell wall.

They say that they are doing  further research to better understand these interactions and to try to find methods for their disruption that will lead to the development of new antibiotic therapies.

What does the NHS Knowledge Service make of this study?

Bacterial resistance is a consequence of widespread and frequent use of antibiotics and new antibiotics that overcome otherwise  resistant bacteria need to be developed. As most antibiotics target the cell wall, this research into the enzyme that may be responsible for some structures in the cell walls will be of interest to scientists.

This is only a single study that has examined the different structures both of the enzyme MurM and the peptidoglycan in two strains of pneumococcal bacteria. The authors themselves state that Streptococcus pneumoniae is unique in its peptidoglycan structure and so extensive further research is needed to investigate if this newly identified protein is present in other strains and other bacteria. It will be some time before it is possible to tell whether there is potential for developing drugs that can target it.

It is too early to say whether these findings will be of any benefit in the fight against resistant bacteria such as MRSA, which is caused by a completely different bacteria.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

UK team in bacteria breakthrough. BBC News, March 12 2008

Links to the science

Lloyd AJ, Gilbey AM, Blewett AM, et al. Characterization of tRNA-dependent Peptide Bond Formation by MurM in the Synthesis of Streptococcus pneumoniae Peptidoglycan. J. Biol. Chem 2008; 283: 6402-6417


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