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Killer bug could deliver medicines

Mycoplasma pneumoniae, such as the colonies shown above, is currently being reworked to deliver drug treatments to patients. Credit: Flickr/Microbe World

A bacterium that causes pneumonia is being redesigned to act as a ‘cell doctor’ that detects and treats disease from inside the human body.

The idea of using bugs as tiny drug couriers is not new: scientists have been engineering viruses to deliver medicines and fix genetic defects for some time.

However, the potential of viruses is limited because they have a small number of genes and because they do not have an active metabolism of their own and cannot respond to the environment or the host. This limits the scope for their engineering for certain medical purposes.

‘Viruses can only carry a limited amount of information,’ said Professor Luis Serrano at the Centre for Genomic Regulation in Barcelona, Spain. ‘They have genes but, unlike bacteria, they do not have a metabolism so they cannot respond to changes in a human cell.’

Using bacteria instead of viruses to deliver treatments to specific parts of the body would provide greater scope for fighting disease because they have more genes to tweak.

However, bacteria are also significantly more complex to work with. For a start, they typically have cell walls – making it difficult for them to communicate with target cells – and they often draw a strong immune response when implanted into humans.

Now, scientists believe they may have found a suitable candidate that has more genes than a virus but is capable of getting into cells to carry out medical missions – and it’s one that we’ve previously associated with disease.

Pneumonia

Mycoplasma pneumoniae can cause bacterial pneumonia in humans, but also ticks many of the boxes required to become a cell doctor. ‘It has no cell wall, it does not cause major inflammation and it can be grown in the lab,’ explained Prof. Serrano, who studied the bug as part of the CELLDOCTOR project, funded by the EU's European Research Council (ERC).

M. pneumoniae is also a very small bacterium. It is roughly the size of a mitochondrion – the subcellular powerhouse that provides our cells with energy. 

Because it is so small and can enter cells without triggering a major immune reaction, Prof. Serrano sees the bug’s potential as a medical tool. 

‘We want to engineer bacteria that can get into the human organism, detect anomalies and repair them.’

Professor Luis Serrano, Centre for Genomic Regulation, Spain

‘We want to engineer a vehicle that can get into the human organism, detect anomalies and repair them,’ he said. ‘It could live inside human cells like a parasite capable of improving health.’

Once inside the target cell, the bacterium would blend in with the other structures already there. But unlike the cell’s other subcellular furniture, the engineered M. pneumoniae bacterium would produce and secrete drugs that a patient needs, or proteins capable of correcting a genetic disease. 

It would not cause disease itself because the researchers have genetically engineered the pneumoniae bacterium to ensure that it is not infectious.

Through the CELLDOCTOR project, Prof. Serrano focused on understanding what makes the bacterium tick before exploring its capacity for delivering drugs, vaccines and genes.

By understanding its genetics and biochemistry, the Barcelona-based researchers developed a deeper understanding of the bug – so that they could redesign a simple organism that would act like a living pill.

Thanks to additional ERC funding, Prof. Serrano was able to take this work one step further and look at specific uses of M. pneumoniae for treating lung and genital tract diseases in a project called MICO PLUNG.

‘Our initial work was pointing towards medical applications for M. pneumoniae and this… project was a chance to direct our efforts towards more clinically applied research,’ he explained.

Respiratory disorders

The bacterium is known to live in lung tissue, so researchers are working on how genetically engineered versions of the bug could deliver therapeutic proteins that could fight against infectious respiratory disorders.

The team also see potential for bacteria to be used as vaccines, deliberately training the immune system to fight unwelcome viruses and bacteria.

Research in this area may change the way we think about bacteria such as M. pneumoniae by turning an old foe into a valuable ally.

Disease-fighting with microbes

  • In 1973, US scientists Professor Stanley Cohen (right) and Dr Herbert Boyer (left) kicked off the field of genetic engineering when they were able to isolate and amplify DNA segments and insert them into an E. Coli host cell with precision. This ability to manipulate the genetic makeup of organisms paved the way for other scientists to reprogramme other organisms, such as viruses, to treat disease.
  • Meanwhile, observations that cancer patients often went into temporary remission when they contracted a virus highlighted the possibility of using viruses to treat diseases. In 1974, a Japanese scientist, Dr Teruo Asada, used small amounts of the mumps virus to treat 90 patients with terminal cancer of various kinds. The virus stopped the development of tumours in at least 37 patients, although radiotherapy and chemotherapy were also necessary. Genetic engineering allowed scientists to tweak the properties of different types of viruses in other studies.
  • In 1990, doctors R. Michael Blaese, W. French Anderson, and Kenneth Culver performed the first sanctioned trial of gene therapy, a technique that treats diseases by delivering new genetic material directly into a patient’s cells to 'correct' their output, often using modified viruses to transport the corrective genes. The doctors took cells from a four-year-old girl called Ashanti DeSilva, who had a condition known as severe combined immunodeficiency disorder, introduced new genetic material and then returned them to her body. It was successful, but short-lived.
  • After two decades of significant progress in human gene therapy, a treatment delivered by the adeno-associated virus became the first gene therapy to receive EU approval. Known as Glybera, it is used to treat patients with a metabolic disorder called lipoprotein lipase deficiency, which causes inflammation of the pancreas. Work is continuing to develop gene therapies for different conditions and to refine how genetic material is delivered to the patient’s cells, including the possibility of using bacteria.

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