Novel theoretical approach to reduce antibiotic resistance

Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance

antibiotic-resistance image
Moffitt researchers have developed a novel mathematical method inspired by Darwinian evolution to use current antibiotics to eliminate or reduce the development of antibiotic-resistant bacteria.
Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteria via NIAID.

2015 Study Abstract

The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different β-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2–4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically ‘steer’ the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic–resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy.

Sources and more information
  • Moffitt Cancer Center Researchers Develop Novel Theoretical Approach to Reduce Antibiotic Resistance, moffitt, October 07, 2015.
  • Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance, PLOS one, DOI: 10.1371/journal.pcbi.1004493, September 11, 2015.

Antibiotic resistance: the human gut microbiome can transport problematic genes between continents

Long distance travelers likely contributing to antibiotic resistance’s spread

bon-voyage image
To reduce antibiotic resistance we need to minimize dispersal rates from the healthcare system, and at the societal level. Suppressing further spread after travelers return to their home countries is crucial, and depends upon having well-informed citizens and a well-functioning public health system. Bon Voyage by Doug.

2015 Study Abstract

Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL) producing enterobacteria and the isolates obtained genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable comparing before and after travel, but with increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold) and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa was positive. Despite deep sequencing efforts, sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

Sources and more information
  • Long distance travelers likely contributing to antibiotic resistance’s spread, American Society For Microbiology, August 20, 2015.
  • The human gut microbiome as a transporter of antibiotic resistance genes between continents, asm, doi: 10.1128/AAC.00933-15, AAC.00933-15, 10 August 2015.

Could antibodies in eggs protect livestock from infection without antibiotics?

Researchers test alternative to livestock antibiotics : eggs

antibodies-in-eggs mage
Animal scientists have stumbled upon a possible way to protect livestock from infection without antibiotics — by feeding them eggs. The eggs contain antibodies, which help keep an animal’s immune system active to fight off disease. Image by Journal Sentinel via UW-Madison.

The chickens weren’t getting sick like they were supposed to.
So the scientists gave them 10 times the normal dose of parasites — enough to produce a severe illness. Still nothing. In fact, the birds looked like they were never infected.
Researchers were trying to hijack the chickens’ immune system to study runaway inflammation.
But the experiment failed. Instead, they stumbled upon a possible way to protect livestock from infection without antibiotics — by feeding them eggs. The eggs contain antibodies, which help keep an animal’s immune system active to fight off disease. ”

… continue reading Researchers test alternative to livestock antibiotics — eggs, Journal Sentinel, Inc., Aug. 17, 2015.

Original publication: UW-Madison startup offers antibiotic alternative to animal producers, UW–Madison News, 6.1.15.

GeneWEAVE Biosciences Inc. bought by Roche for up to $425 million

Roche acquires GeneWEAVE to strengthen offerings in microbiology diagnostics

Roche acquires GeneWEAVE to strengthen offerings in microbiology diagnostics.

Roche has signed a definitive agreement under which it will acquire GeneWEAVE BioSciences, Inc. Roche has been buying the company focused on innovative, clinical microbiology diagnostics solutions, for up to $425 million. With the deal, Roche has further strengthened its commitment to fight superbugs.

Sources and more information
  • Roche acquires GeneWEAVE to strengthen offerings in microbiology diagnostics, geneweave news, August 13, 2015.
  • Roche buys ‘superbug’ diagnostics firm for up to $425 million, Reuters, Aug 13, 2015.

Factory farms, antibiotics and superbugs

Lance Price at TEDxManhattan, 2014

How antibiotics are being used to compensate for the overcrowded, stressful conditions on industrial farms and how that’s creating superbugs that threaten public health.

More information
  • Lance Price is a public health researcher who works at the interface between science and policy to address the growing crisis of antibiotic resistance. In the laboratory, Dr. Price uses cutting-edge DNA sequencing to trace the origins of new antibiotic-resistant pathogens. By analyzing the genomes of bacteria found in humans, food, and livestock, Dr. Price and his colleagues have traced the origins of new superbugs to industrial livestock production. Dr. Price and his colleagues have also begun to broaden the scope of foodborne disease to include urinary tract infections caused by foodborne E. coli.In the policy arena, Dr. Price works with grassroots organizations, NGOs, and policymakers to develop science-based policies to curb antibiotic abuse in food-animal production and stem the emergence of new superbugs. Dr. Price’s work was selected by Discover Magazine as one of the top 100 science stories of 2012. His research has also been covered by top-tier media around the world, including the BBC, New York Times, Los Angeles Times, Chicago Tribune, Scientific American, Men’s Journal, and Fitness Magazine, among others.
  • Video published on 11 Mar 2014 by TEDx Talks.
  • Watch more farming, livestock videos on @DES_Journal YT channel.

The spread of antimicrobial resistance

Antibiotic resistance genes are passed from one bacterium to another

Antibiotic resistance genes are passed from one bacterium to another.

Antibiotic resistance occurs when bacteria that cause infection are not killed by the antibiotics taken to stop the infection. The bacteria survive and continue to multiply, causing more harm. Widespread use of antibiotics promotes the spread of antibiotic resistance. Smart use of antibiotics is the key to decreasing, or even reversing, the spread of resistance.

Sources and more information

What do we do when Antibiotics do not work anymore?

TED Talks video with Maryn McKenna on Antibiotic Resistance

Penicillin changed everything. Infections that had previously killed were suddenly quickly curable. Yet as Maryn McKenna shares in this sobering talk, we’ve squandered the advantages afforded us by that and later antibiotics. Drug-resistant bacteria mean we’re entering a post-antibiotic world — and it won’t be pretty. There are, however, things we can do … if we start right now.

More info and videos

Angela Merkel Statement on Resistance to Antibiotics

68th session of the WHO World Health Assembly in Geneva on 18 May 2015

Angela Merkel, Chancellor of Germany, called on all countries to take steps to curb the spread of antibiotic resistance.

The third issue that Germany would like to address during its G7 Presidency is resistance to antibiotics. We have obtained the advice of the National Academies of Sciences on this issue – and indeed on the subject of neglected tropical diseases. I think this is an issue of crucial importance for the entire human race – for people in developed and less developed countries alike. We must ensure that existing antibiotics remain effective, and that they are used only when medically necessary – not only when treating humans, but animals as well. To this end we want to agree on the strictest standards possible at the G7 meeting, in particular for industrialised countries.

Antibiotics have to be used restrictively, because once pathogens have become resistant to them, it is much, much harder to develop new treatments – in contrast to the situation for example with neglected tropical diseases. The pharmaceutical industry is an important partner in the fight against disease, but it can only provide new products through research and development. I have been told how difficult it is to develop new varieties of antibiotics to replace the old ones. We must therefore tread carefully if we are to make progress. We must pursue a “one health” approach for both humans and animals.

I am delighted that the World Health Assembly has undertaken to draw up the first global action plan to address the problem of antimicrobial resistance. Every country should have a plan of this sort. Only a few days ago the German Cabinet adopted its own antimicrobial resistance strategy. It will require close cooperation in the fields of human and veterinary medicine. ”

Sources and more information

  • Statement by Federal Chancellor Angela Merkel at the 68th session of the WHO World Health Assembly in Geneva on 18 May 2015, WHO Media centre, 18 May 2015.
  • WHO: WHA 68 – Speech by Angela Merkel, Chancellor of Germany, World Health Organization (WHO), 20 May 2015.

The Rise of Superbugs Resistant to Antibiotics

How the deadly misuse of antibiotics is threatening our world

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Antimicrobial Resistance infographic

How antibiotic resistance happens and spreads

Antimicrobial resistance is one of our most serious health threats.
Sources and more information
  • The FDA Just Released Scary New Data on Antibiotics And Farms, motherjones, Apr. 14, 2015.
  • All our posts tagged antibiotics.
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