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MALDI-TOF mass spectrometry

Matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry is a technique used to identify the masses of peptides present.

proteomic fingerprints

A pattern of masses of peptides created by MALDI-TOF mass spectrometry. This pattern can be used to identify a microbe and its antimicrobial medicine resistance profile. 

Immune system

The body's natural defence mechanism against infectious diseases.

Herd immunity

If a high percentage of a population is immune to a disease the disease cannot be passed on because it cannot find new hosts.

Vaccination

A small amount of dead or weakened pathogen is introduced into the body. It prepares the immune system to prevent future infections with the live pathogen.

Antibody

Proteins produced by the plasma cells (B cells, a type of white blood cell) of the immune system in response to a specific antigen..

Pathogen

A micro-organism that causes disease.

Antigen

The protein markers found on the surface of a cell that causes the immune system to produce antibodies against it.

Lysis

Breaking open

Tackling antimicrobial resistance

Tackling antimicrobial resistance requires the help of everyone including members of the public, doctors, the government and the pharmaceutical industry.

Antimicrobial resistance can be tackled in various ways. Some different ways are explained below.

Education and behaviour change

Antimicrobial misuse drives the spread of resistance. A global behaviour change is required to reduce misuse and make a long-term difference.

Public Health England (PHE) started a campaign aiming to improve public awareness and encourage people to use antimicrobials responsibly. More information on the campaign can be found here - Antibiotic Guardian.

It is also important that doctors change prescribing practices to reduce antimicrobial use and ensure that the appropriate antimicrobials are selected. Various apps (eg RxGuidelines app) have been created to help doctors with this.

Rapid diagnostics

Current diagnostic tests take >48 hours to identify the microorganism and assess its resistance profile. To prevent increased sickness and even patient death, doctors must begin treatment before the test results come back. This can often lead to inappropriate antimicrobial usage.

The ability to identify microbes causing infection rapidly could help reduce inappropriate antimicrobial use. One exciting new technology that could revolutionise diagnosis is the Bruker MALDI Biotyper. This technology uses MALDI-TOF mass spectrometry to generate proteomic fingerprints, which are used to rapidly identify a microbe and its resistance profile. Once an organism has been isolated, this technology can be used to identify the organism in ~30 minutes. This technology could enable the appropriate antimicrobial to be selected more quickly.

Diagnosis of Aspergillus fumigatus infections
Aspergillus fumigatus is the causative agent of invasive aspergillosis (a life threatening fungal lung infection). This infection usually only occurs in immunocompromised patients. Diagnosis of Aspergillus fumigatus infections is difficult. Current diagnostic tests take ~72 hours and often provide false negatives. Sadly, Aspergillus fumigatus infections are frequently only identified during post-mortem examination.

The images below show Aspergillus fumigatus isolated from a lung biopsy. The fungus was identified microscopically (left image) and via growth on a petri dish (right image).

(Eloise Ballard)

Sanitation and hygiene

By preventing the spread of infection, we can reduce the spread of resistance. Improving sanitation in the community and in healthcare settings (eg hospitals) is a simple way of doing this. Something as simple as hand washing can make a huge difference.

Resistance surveillance

Surveillance of resistance levels globally is important. It can provide early warning for potential infection outbreaks, guide changes in governmental policy and allow doctors to make informed decisions on what antimicrobial to prescribe.

Vaccine development

Vaccines contain dead, weakened or fragmented pathogens. They present the body with the antigens found on the surface of an active pathogen, or with toxins made by a pathogen, but in a form that cannot cause disease.

Vaccination produces active immunity in people, protecting them from future infection caused by that pathogen. When the majority of a population is vaccinated, the spread of infection is contained. This protects members of the population who cannot be vaccinated (eg elderly people or pregnant women). This is called herd immunity - the animation below explains this idea more.

Show animation full screen in new window

The development of new vaccines could prevent many infections from occurring. This will reduce the requirement for antimicrobials, which will in turn reduce the spread of resistant microbes.

Development of new antimicrobials

Despite significant research into the discovery of novel antimicrobials, no new classes of antibiotics have been discovered since 1978. For more information on how medicines are developed have a look at - Making medicines.

New antimicrobials are desperately required to treat resistant infections. There are few incentives for pharmaceutical companies to develop new antimicrobial medicines. Possible reasons for this include:

  • New antimicrobials should not be widely used- they should be saved as medicines of last resort.
  • Antimicrobials are only taken for short periods of time.
  • Antimicrobial development costs are very high.

There is great demand for incentives to be provided for pharmaceutical companies developing antimicrobials.

Discussion point

What do you think should be done to give pharmaceutical companies incentive to develop antimicrobial medicines?

Use the links below to find out more information:
More must be done to develop new antibiotics, The Guardian
A plan for new antibiotics, Science
Review on antimicrobial resistance, AMR Review

Alternatives to antimicrobials

There are various alternatives to antimicrobial medicines currently under development. Alternative treatments, to which microbes are less likely to develop resistance, would be valuable.

  1. Bacteriophage therapy

    Bacteriophages are natural or synthetic viruses that infect and kill specific bacteria. They do this by injecting their DNA into the bacterial cell. The bacteria then replicates the viral DNA and synthesises new bacteriophages. These new bacteriophages escape the bacteria causing its lysis and death. The antibacterial activity of bacteriophages can be harnessed to treat bacterial infections. The structure of a bacteriophage is shown below.

  2. Lysin therapy

    Lysins are proteins that lyse and kill bacterial cells. A number of studies have shown the potential of lysins to control and treat bacterial infections in humans.

  3. Antibody therapy
    The structure of beta-defensin 4A antimicrobial peptide. This 64 amino acid long human peptide exhibits antibacterial activity.

    Antibodies bind to specific targets- once bound the target is recognised by the immune system for destruction. Antibodies that recognise microbes can be isolated from patients or synthesised. Antibodies are highly specific- this makes them an attractive therapy.

  4. Antimicrobial peptides

    Antimicrobial peptides are short and generally positively charged peptides. These peptides have the ability to kill microbes directly or indirectly by modifying the immune system. Several antimicrobial peptides are currently in clinical trials as antifungal agents.

Click to download the key word summary shown below.

Key word summary