Antibiotic Resistance Through the Ages
Since its serendipitous discovery in 1929, antibiotics have been a cornerstone of modern medicine, transforming once-lethal infections into manageable conditions. The golden age of antibiotics, marked by groundbreaking discoveries and modifications, witnessed these “wonder drugs” effectively combat bacterial infections arising from medical procedures. However, their widespread and indiscriminate use unwittingly fuelled the rise of multidrug-resistant (MDR) bacteria, subdivided into extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains, impervious to existing treatments. In 2011, D’Costa et al, targeted metagenomic analyses were conducted on rigorously authenticated ancient DNA extracted from 30,000-year-old Beringian permafrost sediments. The research aimed to explore the existence of antibiotic resistance genes in ancient microbial communities, challenging the notion that antibiotic resistance is solely a modern phenomenon. The study's findings revealed a diverse collection of genes encoding resistance to β-lactam, tetracycline, and glycopeptide antibiotics. Of particular significance was the confirmation of the structural and functional similarity of the vancomycin resistance element VanA to modern variants. Recent examinations of microbial genomes in modern environments and those coexisting with humans have brought to light a significantly higher concentration of antibiotic resistance genes than previously acknowledged. Furthermore, metagenomic research has disclosed a diverse array of resistance gene counterparts dispersed across various ecological niches. This widespread prevalence of antibiotic resistance elements challenges the notion that resistance is a recent development and instead suggests a more comprehensive and ancient history of resistance (D’Costa et al, 2011).
In 2021, Lopatkin and colleagues made a significant discovery, revealing that metabolic mutations can develop as a response to antibiotic treatment. These mutations not only bestow resistance but are also notably widespread in clinical pathogens. This finding challenges the conventional understanding of the three general categories of antibiotic resistance, suggesting that they may not be as representative or comprehensive as previously believed. In essence, this study suggests that metabolic adaptation could represent a distinct class of resistance mechanisms that go beyond mere tolerance, as cells also modify their metabolic responses to mitigate the toxic effects of antibiotics (Lopatkin et al, 2021).
In a 2011 review by Andersson and Hughes, it was highlighted that the antibiotic resistance predicament, which has evolved over the last six decades due to extensive and often inappropriate antibiotic use, appears to be a persistent and formidable challenge for the foreseeable future. The assessment drew upon theoretical reasoning, mathematical models, empirical studies, and clinical interventions, collectively suggesting that even if efforts were made to curtail antibiotic consumption, resistant bacterial strains would likely endure and only slowly, if at all, be overtaken by their susceptible counterparts. The review extensively explored the diverse mechanisms and processes contributing to the persistence of resistance determinants carried on both chromosomal and plasmid elements. It also contemplated strategies to harness these mechanisms to potentially reverse the problem. Of particular significance was the observation that exceedingly low antibiotic concentrations could favour the enrichment of resistant bacteria, with implications for the environmental release of antibiotics contributing to the selection for resistance (Andersson and Hughes, 2011).
The causes of antibiotic resistance, encompass human behaviour across various societal levels. These are parallel with the global implications of climate change. Despite numerous attempts to address antibiotic resistance and its complex dimensions, a critical lack of coordinated action, particularly in the political arena, prevails both nationally and internationally (Laxminarayan et al, 2013).