Over the past 70 years antibiotics have been hugely important in our defence against infectious diseases caused by bacteria. However, bacterial resistance to antibiotics is becoming a global public health problem and if we are to develop new treatments for antibiotic-resistant bacteria we need to understand how they become resistant. This includes investigating more about how the entire bacterial cell works. Studies that analyse changes in the protein composition of bacterial cells after antibiotic treatment are helping us to become more familiar with the processes involved in resistance.
The entire set of proteins expressed by a cell, tissue or an organism at any one time is known as the proteome and the term ‘proteomics’ is used to describe the study of the proteome.
In PHE, one of the ways that we analyse bacterial proteins is using mass spectrometry (MS) technology. This has helped our scientists to understand more about which bacterial proteins are coded for by which particular parts of the genome. We know that the genome includes coding information for every protein and we have been able to demonstrate that some proteins that are coded for are not always produced. This means that protein production depends not only on the information in the genomic code but also on other factors, such as the environment in which the bacteria are growing.
This is particularly important in outbreaks of disease where some bacteria seem to be able to increase their ability to cause disease. PHE scientists are using a newly developed type of MS technology to understand more about these changes and this information could have wide applications in many human diseases involving infection including cancer.
Understanding which bacterial proteins are likely to be produced in different environmental conditions will help us to improve our understanding of the how bacteria cause disease. This will lead to improved diagnosis and treatment of individual infections and more effective control of wider outbreaks of infectious diseases that can affect entire populations. For example, people with cystic fibrosis, an inherited disease that results in thick sticky mucus lining the lungs, are often infected with a bacterium called Pseudomonas aeruginosa. This infection damages their lung function. We know that in the early stages of infection the bacteria live freely in the lung but over time they transform into sticky mucoid layers called biofilms which protect the bacteria from antibiotics. PHE proteomic studies are helping us to understand how the changes occur that enable the bacteria to remain in the lungs so we can identify ways of reducing the damage to the lung tissue that is caused by P.aeruginosa infection.
One particular MS technology, known as MALDI-TOF MS, is used in many NHS microbiology testing laboratories to identify bacteria inexpensively in only a few minutes. PHE scientists have also found that MS analyses are even more effective if they are carried out in conjunction with genome sequencing (to understand the genetic code). There is a term for bringing proteomic and genomic technologies together – ‘proteogenomics’.
Our scientists recognise that genetic mutations in bacteria will lead to the emergence of altered proteins, including toxins, or enzymes such as those responsible for some bacterial resistance to antibiotics. We know that this is a rapidly moving field and new technologies will continue to emerge that will complement or perhaps replace our current approaches in subsequent years. PHE is working with many different partners and stakeholders to lead the development of proteogenomics and the related technologies for better health outcomes and responses in cases of infection.
I’d be interested in your thoughts: what do you see as the most promising future solutions to the problem of antibiotic resistant bacteria?