Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Adapting to clogged airways makes common pathogen resist powerful drugs

10.02.2010
Mutations that enable Pseudomonas to thrive in cystic fibrosis lung secretions may also guard the bacteria against antibiotics

People with cystic fibrosis, an inherited disease that clogs airways with thick mucous, frequently have lung infections that defy treatment. While the life expectancy for children with cystic fibrosis has increased over the past few decades, many lives are still shortened in young adulthood by the ravages of lung infections.

These chronic infections are often caused by common, environmental microbes that mutate in ways that let them live and thrive in viscous lung secretions. The same adaptations also make the pathogens less likely to be killed off by powerful antibiotics, according to a recent study led by Dr. Lucas "Luke" Hoffman, University of Washington (UW) assistant professor of pediatrics.

Surprisingly, he added, the pathogens don't need any previous exposure to the antibiotics to resist their effects. The results were published in the latest edition of PLoS Pathogens.

The researchers looked at Pseudomonas aeruginosa, a microbe that can infect a cystic fibrosis patient early in life and then undergo various changes as it establishes a chronic lung infection. Pseudomonas aeruginosa with specific alterations tend to give patients a poor outcome. Some of those alterations diminish the chances of eradicating the infection with antibiotics.

It's believed that these adaptive alterations in Pseudomonas, all of which are caused by genetic changes, could be selected for by the environment inside a patient's airways, the researchers noted. Characteristics that facilitate microbial survival begin to emerge.

The specific airway conditions that select for these genetic changes, Hoffman said, remain unclear. "But," he added, "we have some clues from what is known about airway mucus."

From the point of view of Pseudomonas, the physical properties of cystic fibrosis mucus, Hoffman said, "make it a great place for the stuff people routinely breathe in to set up shop." Cystic fibrosis secretions contain a lot of nitrates and amino acids, which Pseudomonas can use to grow.

Inside mucus plugs oxygen levels are low. Some Pseudomonas strains can live in this oxygen-poor, nutrient-rich environment. Hoffman and his team found that a mutation that occurs commonly in Pseudomonas from cystic fibrosis patients allows the pathogen to grow better in the nutrient environment in cystic fibrosis secretions. This particular mutation inactivates a gene named lasR. Pseudomonas with this mutation apparently undergo a metabolic shift: consuming less oxygen while utilizing nitrate more efficiently. lasR mutant bacteria also can handle oxidative stress resulting from an imbalance of damaging substances called free radicals forming faster than they can be detoxified.

One source of oxidative stress encountered by Pseudomonas is the antibiotic treatment that is frequently given to people who have cystic fibrosis. Antibiotics like ciprofloxacin and tobramycin kill bacteria partly by inducing the overproduction of free radicals and causing oxidative stress. Hoffman and his team found that, because these mutant microbes are resistant to oxidative stress, they were relatively resistant to these antibiotics when grown in conditions that were like cystic fibrosis mucus.

"We learned that simply by adapting to the conditions inside the airways of cystic fibrosis patients, mutated Pseudomonas can withstand the effects of ciprofloxacin and tobramycin," Hoffman said. They did not need any previous exposure to these antibiotics to reduce their susceptibility.

Hoffman and his team suspect that Pseudomonas is not the only microbe that can do this. Some of the characteristics conferred by the mutation in Pseudomonas are also exhibited in other microbes found in chronic lung infections, such as tuberculosis or the fungal pathogen, Cryptococcus neoformans, Hoffman noted. Metabolic shifts may be a way many microbes get the upper hand over their hosts – and over antibiotics.

This report, Hoffman said, may point to new ideas for treating chronic lung infections. Luckily, colonies of Pseudomonas with the lasR mutation are relatively easy to identify in hospital laboratories by their distinctive iridescent sheen. Because lasR mutant Pseudomonas has been associated with worse outcomes in cystic fibrosis patients, indentifying Pseudomonas with the lasR mutation may be of prognostic value and may indicate the need for treatment with specific antibiotics like monobactams, tetracyclines, or polymyxin, whose mode of action differs from ciprofloxacin and tobramycin. Other treatment methods may be targeted at preventing adaptive changes, such as the lasR mutation, in Pseudomonas, the researchers said.

In addition to Hoffman, scientists on this study were Anthony Richardson, Ferric Fang, and Samuel Miller from the UW Department of Microbiology; Laura Houston and Jane Burns from the UW Department of Pediatrics; Hermantha Kulasekara and Mikkel Klausen from the UW Department of Genome Sciences; Wilm Martens-Habbena and David Stahl from the UW Department of Civil and Environmental Engineering; and Daniel Hassett from Department of Molecular Genetics, Biochemistry and Microbiology at the University of Cincinnati College of Medicine in Ohio. Fang and Miller both hold appointments in the UW Department of Medicine. Fang is also with the UW Department of Laboratory Medicine and Miller is also with UW Department of Genome Sciences.

The research was funded by grants from the Cystic Fibrosis Foundation, the National Institutes of Health, and the National Science Foundation.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>