Genomics Data and Mathematical Modeling Illuminate Antibiotic Resistance Success in E. coli
Pathogens resistant to drugs are becoming increasingly common, largely because of the excessive and inappropriate use of antibiotics. To a degree, the emergence of antimicrobial resistance (AMR) is caused by mutations in the genome of bacteria, while sometimes it is due to genes jumping between bacteria. Either way, when resistance already is in place, the bacteria carrying it can receive a boost to spread faster from the use of antibiotics in treatment of various infections.
A study published in the esteemed Lancet Microbe journal provides further information on the ways in which the ability of the Escherichia coli bacterium to resist antibiotics varies over time and between countries. E. coli is a common intestinal bacterium that causes, for example, urinary tract infections, severe bloodstream infections and meningitis, the latter particularly in neonates.
An international research group led by Professor Jukka Corander investigated which factors affect the prevalence of E. coli bacteria resistant to antibiotics in the population. The study also provided further information on the effect of the use of various types of antibiotics on the increasing prevalence of certain strains of E. coli.
In the analysis, it was found that the widespread use of only one type of antibiotic was clearly linked to the prevalence of multi-drug resistant bacterial strains. Infections caused by these strains are difficult to treat, and they have spread globally in the past 20 years.
“We also demonstrated that the causal relationships between the use of various types of antibiotics and the prevalence of corresponding resistance are very complex. Other differences in the E. coli genome also affect the extent to which certain bacterial strains benefit from genes and mutations that create resistance”, Corander says.
Causal analysis was made feasible by an extensive longitudinal data
What made the study exceptional was that, for the first time, researchers were able to quantify the causal effect of the use of different types of antibiotics on the variation of E. coli variants resistant to these antibiotics.
The researchers used the isolate database of the British Society for Antimicrobial Chemotherapy of E. coli bacteria found in patients’ blood samples, on which they carried out whole-genome sequencing at the Wellcome Sanger Institute in Cambridge. This produced sequencing data mapping out the genetic variation of E. coli bacteria from 2012 to 2017.
The data were combined with whole-genome E. coli data previously published in the United Kingdom and Norway to establish parallel collections of bacterial genomes from 2001 to 2017.
Genes and human activity underlying the prevalence of resistance
The increasing prevalence of antimicrobial resistance means that the number of deaths caused by bacteria is also increasing, as drugs are no longer effective against pathogens.
“It’s very important to understand how, on the one hand, genetic factors and, on the other, human activity, such as antibiotic consumption, global mobility and food production, affect the prevalence of antimicrobial resistance and bacterial strains that cause infections. Comprehensive genomic data facilitate to determine which factors affect the prevalence of antimicrobial resistance and how much. This way, we have a better chance of turning the tide on AMR,” Corander says.
“It’s also extremely important for research funders to understand the gravity of the situation. Without basic scientific research of a high standard, we will be at a loss what to do about the tsunami of antimicrobial resistance.