Scientists from the University of Cambridge Department of Biochemistry and Papworth Hospital adult CF clinic found that the genome sequences of a bacterium called Pseudomonas aeruginosa could be different, even among co-habiting isolates obtained from a single person. P. aeruginosa causes infections that often kill CF patients, and this inherent genetic diversity may be a factor that makes treatment more difficult.
A colourised scanning electron micrograph (SEM) of a number of Pseudomonas aeruginosa bacteria. Image: Janice Haney Carr
CF is the most common inherited life-threatening disease in the developed world. Patients with CF often die from secondary infections caused by bacteria like P. aeruginosa, and these can stubbornly resist treatment with antibiotics.
Dr Martin Welch of the University of Cambridge led the study. He explains “Previous genomic analyses seemed to indicate that the bacterial populations in these patients were rather uniform and did not display much genetic variation. However, this was contrary to what the clinicians treating the patients experienced. They found that, even amongst the bacterial colonies isolated from a single patient, a range of antibiotic resistance profiles was often evident. This is a strong indication that these isolates are likely to be genetically different.”
To examine this possibility further, the Cambridge team used state-of-the-art DNA sequencing to decipher the genome sequences of randomly chosen pairs of bacterial isolates, with each pair being taken from a different CF patient. Pairs of isolates from three patients were studied in all. The study revealed that the genome sequences of the isolates comprising each pair differed from one another, sometimes substantially.
Dr Welch continues “Whilst this is only a small study, it does seem to confirm what clinical microbiologists have long suspected – that the population of bacteria within a patient can be quite diverse. This diversity can potentially make the infection much harder to resolve, since genomic differences can affect the way a bacterium responds to antibiotics. A more detailed understanding of the genomic makeup of the bacterial population could lead to improved treatment strategies for these patients.”
Much of this work was carried out by Jade Chung, a BBSRC-funded PhD student who collaborated closely with Illumina, the makers of market-leading sequencing technology.
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