Whole‐genome sequencing for combatting antibiotic resistance

Abstract

The current special issue of Drug Development Research includes overview and original research articles addressing novel approaches and new tentative therapeutics that will hopefully assist in the ongoing battle against microbial antibiotic resistance. Antibiotic resistance is among the key challenges facing contemporary medicine in the 21st century. Rising numbers of critically ill patients die as a result of infections driven by antibiotic resistant bacteria (San Millan, 2018). Recent estimates predict that that by 2050 more people will die from antibiotic-resistant bacterial infections than from cancer (O Neill, 2016). Population growth, increased urbanization, overcrowded hospitals, contamination of scarce water sources, industrialization of animal farming, and global warning all play role in the increased rate of antibiotic resistant bacterial and fungal infections. The alarming and rising trend of antibiotic resistance in hospitals is believed to result from inappropriate overuse of antibiotics by clinicians (Chatterjee et al., 2018). According to a recent report by The World Health Organization (WHO), “while there are some new antibiotics in development, none of them are expected to be effective against the most dangerous forms of antibiotic-resistant bacteria” (World Health Organization website, accessed November 1st, 2018). The WHO also warn that “Without urgent action, we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill”. Facing this grim forecast, Nature Editors recently called upon clinicians, pharmaceutical companies, and researchers to “come together to suggest ways to break the deadlock on finding better ways to prescribe antibiotics” (Nature Editorial, October 17, 2018). Antibiotic resistance may result from new mutations, or may involve bacterial transposons, mobile genetic sequences that may include genes for antibiotic resistance. Transposons can “jump” into altered locations in the bacterial genome, or be exchanged with other bacteria within plasmids during conjugation (Jeong et al., 2018; Osborn & Böltner, 2002). Bacterial transposons typically carry, in addition to the sequence which allows them to jump to new DNA locations in the bacterial genome, genes coding for functions other than the transposition itself, and such genes may transmit antibiotic resistance. Transposons can relocate from a plasmid to other plasmids within or between bacterial species, thereby leading to the transmission of genes affording antibiotic resistance among different bacteria (Babakhani & Oloomi, 2018). For example, transposons are often responsible for transmission of antibiotic resistance in Enterobacteriaceae and Enterococcaceae, which include some of the most common nosocomial pathogens (San Millan, 2018); multi-antibiotic resistant bacterial strains, termed “superbugs”, can be generated in this manner. Antibiotic resistance of bacteria is not necessarily transferred as such, but may rather be created by a mutation resulting from the moving of a genetic element to a new location, so that this move generates an altered protein-coding sequence. Barbara McClintock s discovery of transposons (McClintock, 1950), albeit originally studied in maize, earned her the 1983 Nobel Prize in Physiology or Medicine. Horizontal transfer of bacterial antibiotic resistance following plasmid exchange during bacterial conjugation sometimes creates “superbugs” that disseminate overwhelmingly in clinical settings. It was recently shown that most antibiotic resistant pathogens are known or predicted to be naturally transformable, raising concerns that horizontal transfer underlies the spread of antibiotic resistance and drives the evolution of deadly “superbugs” by bringing together several antibiotic resistance genes into the same bacterial cells (Lerminiaux & Cameron, 2018). One such notable example is the Escherichia coli sequence type 131 (ST131), which has emerged around two decades ago as the most predominant pathogenic lineage worldwide (Stoesser et al., 2016). Another notable example is the antibiotic resistance in Klebsiella pneumoniae sequence type 11 (ST11) which has caused fatal hospital infections globally (Lee et al., 2016).