Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Resistance to last-line antibiotic makes bacteria resistant to immune system

21.05.2013
Bacteria resistant to the antibiotic colistin are also commonly resistant to antimicrobial substances made by the human body, according to a study in mBio®, the online open-access journal of the American Society for Microbiology.

Cross-resistance to colistin and host antimicrobials LL-37 and lysozyme, which help defend the body against bacterial attack, could mean that patients with life-threatening multi-drug resistant infections are also saddled with a crippled immune response.

Colistin is a last-line drug for treating several kinds of drug-resistant infections, but colistin resistance and the drug's newfound impacts on bacterial resistance to immune attack underscore the need for newer, better antibiotics.

Corresponding author David Weiss of Emory University says the results show that colistin therapy can fail patients in two ways. "The way that the bacteria become resistant [to colistin] allows them to also become resistant to the antimicrobials made by our immune system. That is definitely not what doctors want to do when they're treating patients with this last line antibiotic," says Weiss.

Although it was developed fifty years ago, colistin remains in use today not so much because it's particularly safe or effective, but because the choices for treating multi-drug resistant Acinetobacter baumannii and other resistant infections are few and dwindling. Colistin is used when all or almost all other drugs have failed, often representing a patient's last hope for survival.

Weiss says he and his colleagues noted that colistin works by disrupting the inner and outer membranes that hold Gram-negative bacterial cells together, much the same way two antimicrobials of the human immune system, LL-37 and lysozyme, do. LL-37 is a protein found at sites of inflammation, whereas lysozyme is found in numerous different immune cells and within secretions like tears, breast milk, and mucus, and both are important defenses against invading bacteria. Weiss and his collaborators from Emory, the CDC, Walter Reed Army Institute of Research, and Grady Memorial Hospital in Atlanta set out to find whether resistance to colistin could engender resistance to attack by LL-37 or lysozyme.

Looking at A. baumannii isolates from patients around the country, they noted that all the colistin-resistant strains harbored mutations in pmrB, a regulatory gene that leads to the modification of polysaccharides on the outside of the cell in response to antibiotic exposure. Tests showed a tight correlation between the ability of individual isolates to resist high concentrations of colistin and the ability to resist attacks by LL-37 or lysozyme.

This was very convincing, write the authors, that mutations in the pmrB gene were responsible for cross-resistance to LL-37 and lysozyme, but to get closer to a causative link between treatment and cross-resistance, they studied two pairs of A. baumannii isolates taken from two different patients before and after they were treated for three or six weeks with colistin. The results helped confirm the cross-resistance link: neither strain taken before treatment was resistant to colistin, LL-37, or lysozyme, but the strains taken after treatment showed significant resistance to colistin and lysozyme. (One post-colistin isolate was no more or less resistant to LL-37 than its paired pre-colistin isolate.) Like the resistant strains tested earlier, both post-colistin isolates harbored crucial mutations in the pmrB gene that apparently bestow the ability to resist treatment.

The authors point out that the apparent link between resistance to colistin and cross-resistance to antimicrobial agents of the immune system could well extend to other pathogens that are treated with colistin, including Pseudomonas aeruginosa and Klebsiella pneumoniae. Weiss says he plans to follow up with studies to determine whether this bears out.

For Weiss, the problems with colistin are symptomatic of a much larger trio of problems: increasing levels of drug resistance, cuts in federal funding for antibiotic research, and lack of incentives for pharmaceutical companies to invest in antibiotic R&D. "We don't have enough antibiotics, and it's really important for the research community and the public to support increases in funding for research to develop new antibiotics," says Weiss.

"We got complacent for a while and the bugs are becoming resistant. This is something we can reverse - or make a lot better - if we have the resources."

mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.

The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Jim Sliwa | EurekAlert!
Further information:
http://www.asmusa.org

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>