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Antibiotic

What You Need to Know about the Threat of Antibiotic Resistance

Antibiotic resistance has become a global health problem during the past three decades due to the emergence of dangerous, resistant strains with disturbing regularity, something that Sir Alexander Fleming, the discoverer of penicillin, warned us about during his Nobel Prize speech in 1945.

In April this year a new groundbreaking report was put forward by the UN and international agencies that called for immediate action to avert a potentially disastrous antibiotic-resistance crisis.

Based on predictive analytics, antibiotic-resistance could mean 10 million deaths each year by 2050 and damage to the economy as catastrophic as the 2008 global financial crisis. Antibiotic resistance can affect anyone, of any age, in any country.

And multidrug-resistant tuberculosis is only part of the issue. Common diseases, including respiratory and urinary tract infections, gastrointestinal infections, sexually transmitted infections are becoming untreatable while major surgeries are jeopardised. Are the “bad bugs” taking over? And what led us to this?

First of all, let’s put things into perspective. Bacteria are present across all habitats and the total number of bacterial species is estimated to exceed one million [1] but only 10–20 bacterial species are currently known to be human pathogens, with hundreds of bacteria being merely opportunistic (capable of causing disease but only in certain conditions).

One of the mechanisms by which pathogenic bacteria acquire antibiotic resistance came to light just a week ago when a group of French researchers reported that E. coli displays a well-conserved membrane pump that shuttles antibiotics out of the cell while at the same time receiving DNA from neighbouring bacteria that codes for a drug-resistant protein (2). 

This DNA transfer is made possible by what is called horizontal gene transfer (HGT), the core mechanism for the evolution of antibiotic resistance. HGT can take place by conjugation, transformation and transduction. In conjugation, DNA is transferred in cell contact, whereas the other two don’t require cell-to-cell contact. This means bacteria can change their genetic make-up practically instantly to defend themselves against antibiotics.

Another mechanism of acquiring resistance is through chromosomal mutations. Gram-negative bacteria can also produce an enzyme, extended-spectrum beta-lactamase that has the ability to break down commonly used antibiotics, such as penicillins and cephalosporins and render them ineffective for treatment. And who knows what else we’ll discover in the future (3).

Based on this knowledge, the bottom line is rather clear: bacteria can easily outsmart us when it comes to biological warfare tactics and are a lot faster to adapt to a hostile environment. This shouldn’t come as a surprise since in evolutionary terms, bacteria have lived on this planet for about 3.5 billion years, which gave them plenty of time to learn a lot of defensive tricks, while humans are the newbies whose evolution started only 300,000 years ago.

With all this in mind, is the search for new antibiotics still the goal? While the pharmaceutical industry has been showing a flagging interest in antibiotics (with only 1.6% of drugs in clinical development by the world’s 15 largest drug companies in 2004 for example), just the other day a new compound capable of killing drug-resistant superbugs made headlines (4, 5). Obviously when dealing with an acute infection, antibiotics can prove life-saving but their short-term benefits should never blind us to their long-term negative consequences.

By this I mean that the overuse and misuse of antibiotics hasn’t only led to the evolution of resistant strains but it also altered the natural composition of the microbiome in a way that is deleterious to health and these changes persist long after the antibiotics regimen is done. Experts are now talking about lack of microbial diversity as one of the reasons for decreased immune system activity and susceptibility to infections. Considering that 80% of the immune system is located in the gut, this makes perfect sense.  A healthy, diverse microbiome modulates metabolic and immunologic processes, and protects against colonisation by invasive pathogens. Disruption of the finely tuned gut flora has profound effects on the protective barrier and results in disturbance of the metabolism and absorption of vitamins, translocation of toxins, overgrowth of yeast and/or Clostridium difficile, one of the gram-positive, opportunistic pathogens, and other life-threatening infections (6, 7), creating a vicious circle of ill-health that is very difficult to correct.

The problem of antibiotic resistance however extends beyond antibiotic misuse in humans. There is widespread antibiotic application in livestock, with dairy farming involving surplus use of antibiotics as prophylactic and growth promoting agents. This application of antibiotics is highly problematic since a dairy animal also poses a serious risk of transmission of resistant strains to humans and the environment (8). In other words, solving the problem of antimicrobial resistance in a single environment, such as in the clinic, will prove ineffective given that in bacteria, mobile genetic elements (MGEs) and the drugs themselves move among human, animal and environmental compartments (9).

And this is one of the novelties of the aforementioned report: it recognises that human, animal, food and environmental health are closely interconnected, calling for a coordinated “One Health” approach that requires not only prudent use of antimicrobials by professionals, development for new technologies to combat antimicrobial resistance, but also to urgently phase out the use of critically important antimicrobials as growth promoters in agriculture.

Without urgent action, we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill. This being a global health crisis with multiple dimensions, generating effective solutions in the most efficient manner requires active collaboration and communication among scientists representing different disciplines: physicians, microbiologists, evolutionary biologists and environmental scientists—among others.

And this is exactly what events like Xpomet© Medicinale are for. “Our vision for Xpomet© Medicinale Festival is to connect all key stake holders in next-generation healthcare and allow technologies to be translated within and from outside the healthcare field”, said Xpomet© founder, Ulrich Pieper.

We look forward to welcoming you at the upcoming Xpomet© Medicinale Festival, taking place between 10–12 October 2019 in Berlin.

REFERENCES

  1. Taylor LH et al. (2001) Risk factors for human disease emergence. Philos Trans R Soc Lond B Biol Sci. 
  2. S. Nolivos et al., (2019) “Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer,” Science
  3. Rawat D, Nair D. Extended-spectrum β-lactamases in Gram Negative Bacteria. J Glob Infect Dis. 2010;2(3):263–274
  4. University of Sheffield. (2019, May 28). New compound which kills antibiotic-resistant superbugs discovered. ScienceDaily. Retrieved June 1, 2019
  5. Kirsty L. Smitten et al. (2019) Using Nanoscopy To Probe the Biological Activity of Antimicrobial Leads That Display Potent Activity against Pathogenic, Multidrug Resistant, Gram-Negative Bacteria. ACS Nano20191355133-5146
  6. Levy, J. (2000). The effects of antibiotic use on gastrointestinal function. Am J Gastroenterol 95, S8–S10
  7. Sullivan, A., Edlund, C. & Nord, C. E. (2001). Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis 1, 101–114
  8. Sharma Chetan, Rokana Namita et al. (2018) Antimicrobial Resistance: Its Surveillance, Impact, and Alternative Management Strategies in Dairy Animals. Front. Vet. Sci.
  9. Woolhouse ME, Ward MJ. et al (2013) Sources of antimicrobial resistance. Science 341, 1460–1461