Secrets of a 'superbug': what makes Pseudomonas bacteria so deadly?

Pseudomonas aeruginosa can be a dangerous bacterium. It is one of the main causes of serious hospital-acquired infection in the UK.^1,2,3,4 It is also a leading cause of death among people with cystic fibrosis.^5,6 Researchers are studying the bacterium's genetic make-up to find out what makes it so dangerous - an important step if we are to develop better ways to protect people from this deadly infection.

Contents

• What's the problem and who does it affect?
• What is the project trying to achieve?
• What are the researchers' credentials?
• Who stands to benefit from this research and how?
• References

What's the problem and who does it affect?

A dreaded and deadly infection

The healthy amongst us have little to fear from Pseudomonas aeruginosa bacteria. But for some people the bacteria can be deadly. They can kill people in our hospitals within 24 hours of striking. They can also infect the lungs of people with cystic fibrosis, frequently contributing to an untimely death. Pseudomonas bacteria are in fact a major cause of hospital-acquired infection, with an estimated 10,000 cases each year in the UK alone.^4,7,9 All too often, infection is severe and life-threatening, leading to pneumonia or septicaemia. Initial fever, cough, shortness of breath and chest pain can progress worryingly quickly until the patient is at substantial risk of generalised organ failure. Sadly, up to half of victims who develop pneumonia or septicaemia die.^1,2,3Survivors can be left disabled for life. Pseudomonas bacteria are also dreaded by people with cystic fibrosis, a common inherited disorder. Up to 80% of adults with cystic fibrosis carry the bacteria in their lungs.¹⁰ Infection contributes to a gradual but relentless deterioration in sufferers' breathing and general state of health, markedly impacting on daily activities and frequently proving fatal.

What is the project trying to achieve?

Genetic weapons of Pseudomonas bacteria

It is difficult to treat people with Pseudomonas infections. The bacteria have long been notorious for their resistance to antibiotics. More recently, scientists have discovered that individual Pseudomonas bacteria differ considerably from one another, meaning we are not necessarily fighting a single foe. The bacteria's genetic make-up differs, as does their virulence - their ability to cause disease. Some strains seem particularly good at spreading from one person to another, resisting antibiotics, surviving in the environment, or even causing death. They are also constantly evolving. In this project, researchers are studying the genetic differences between a wide spectrum of different Pseudomonas aeruginosa bacteria. They are identifying and sequencing sets of genes that enable the bacteria to cause serious infections in man, and studying the role of these genes. They aim to emphasise the enormous genetic diversity between different Pseudomonas bacteria by studying strains collected as far apart as Liverpool and Melbourne, from people with and without cystic fibrosis.

What are the researchers' credentials?

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The project leader, Dr Kumar Rajakumar, is a leading expert in the study of bacterial genomes and the molecular mechanisms that bacteria utilise in causing disease. He has published in excess of 25 primary research papers that describe key phenomena in several important bacterial pathogens that cause disease in humans. The other members of the project team have a great wealth of expertise in a range of specialisms, including modelling infections, the immune processes that take place within the lungs, cystic fibrosis and the clinical management of infections. This combination of skills means the team is ideally placed to succeed in this study. The research will take place within the Department of Infection, Immunity and Inflammation, at the University of Leicester. The Department has a well-developed infrastructure and a long track record of conducting research of the highest standard, which will benefit the research team enormously.

Who stands to benefit from this research and how?

Helping prevent, diagnose and treat infection

The researchers are hoping to identify the bacterial genes that make Pseudomonas aeruginosa so deadly to vulnerable people. This work is of fundamental importance to the future development of better ways to prevent, diagnose and treat Pseudomonas infections. It may lead to new screening tools that can tell us whether people have been infected with a particularly nasty strain of the bacteria. Researchers believe this could save lives by allowing better infection control procedures, as well as early and aggressive antibiotic therapy when needed. The discovery of disease-causing genes may also contribute to the development of new antibiotics, a vital area of need as Pseudomonas bacteria are increasingly resistant to most currently available antibiotics. Everyone who is at risk of Pseudomonas infection may benefit in the future. Pseudomonas aeruginosa causes an estimated 10% of all hospital-acquired infections in the UK.^4,7,8 Those most at risk include the elderly, people with cancer, severe burns or weakened immune systems, and people who need artificial ventilation. People with cystic fibrosis may benefit too. More than 7,000 people in the UK have cystic fibrosis,¹¹ with the much-dreaded Pseudomonas bacteria being a leading cause of death.

References

1. Shaw MJ. 2005. Ventilator-associated pneumonia. Curr Opin Pulm Med 11:236-41.

2. Chastre J, Fagon JY. 2002. Ventilator-associated pneumonia. Am J Respir Crit Care Med 165: 867-903.

3. Van Delden C. 2007. Pseudomonas aeruginosa bloodstream infections: how should we treat them? Int J Antimicrob Agents 30 Suppl 1: S71-5.

4. Spencer RC. 1996. Predominant pathogens found in the European Prevalence of Infection in Intensive Care Study. Eur J Clin Microbiol Infect Dis 15:281-5.

5. Hoiby N, Frederiksen B, and Pressler T. 2005. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros 4 Suppl 2:49-54.

6. Murray TS, Egan M, and Kazmierczak BI. 2007. Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients. Curr Opin Pediatr 19:83-8.

7. Jones RN, Kirby JT, Beach ML, Biedenbach DJ, and Pfaller MA. 2002. Geographic variations in activity of broad-spectrum beta-lactams against Pseudomonas aeruginosa: summary of the worldwide SENTRY Antimicrobial Surveillance Program (1997-2000). Diagn Microbiol Infect Dis 43:239-43.

8. Aloush, V, Navon-Venezia S, Seigman-Igra Y, Cabili S, and Carmeli Y. 2006. Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact. Antimicrob Agents Chemother 50:43-8.

9. Mayor S. 2000. Hospital-acquired infections kill 5000 patients a year in England. BMJ 321:1370.

10. Doring G, Conway SP, Heijerman HGM, Hodson ME, Hoiby N, Smyth A, Touw DJ for the Consensus Committee. 2000. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16:749-67. 11. UK CF Database / Cystic Fibrosis Trust, Annual Data Report 2004, University of Dundee, http://www.cystic-fibrosis.org.uk/pdfs/annualreport/AuditReport2004.pdf