Abstract
BackgroundThe emergence and prevalence of multidrug resistant (MDR) pathogenic bacteria poses a serious threat to human and animal health globally. Nosocomial infections and common ailments such as pneumonia, wound, urinary tract, and bloodstream infections are becoming more challenging to treat due to the rapid spread of MDR pathogenic bacteria. According to recent reports by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), there is an unprecedented increase in the occurrence of MDR infections worldwide. The rise in these infections has generated an economic strain worldwide, prompting the WHO to endorse a global action plan to improve awareness and understanding of antimicrobial resistance. This health crisis necessitates an immediate action to target the underlying mechanisms of drug resistance in bacteria.ResearchThe advent of new bacterial genome engineering and synthetic biology (SB) tools is providing promising diagnostic and treatment plans to monitor and treat widespread recalcitrant bacterial infections. Key advances in genetic engineering approaches can successfully aid in targeting and editing pathogenic bacterial genomes for understanding and mitigating drug resistance mechanisms. In this review, we discuss the application of specific genome engineering and SB methods such as recombineering, clustered regularly interspaced short palindromic repeats (CRISPR), and bacterial cell-cell signaling mechanisms for pathogen targeting. The utility of these tools in developing antibacterial strategies such as novel antibiotic production, phage therapy, diagnostics and vaccine production to name a few, are also highlighted.ConclusionsThe prevalent use of antibiotics and the spread of MDR bacteria raise the prospect of a post-antibiotic era, which underscores the need for developing novel therapeutics to target MDR pathogens. The development of enabling SB technologies offers promising solutions to deliver safe and effective antibacterial therapies.
Highlights
Genome engineering tools and their applications for countering bacterial infections A number of methods have been developed for engineering bacterial genomes with varying degrees of efficiency, specificity and broad host applicability [19]
The prevalent use of antibiotics and the spread of multidrug resistant (MDR) bacteria raise the prospect of a postantibiotic era, which underscores the need for developing novel therapeutics to target MDR pathogens
The integration of engineering principles and biology in the last decade has opened up new avenues for development of novel therapeutics in treating diseases
Summary
The integration of engineering principles and biology in the last decade has opened up new avenues for development of novel therapeutics in treating diseases. By rational combination of gene parts, biosynthesis can be potentially reprogrammed for generation of novel small molecules for therapeutic purposes [48] This is further facilitated by in silico whole genome mining and software algorithms that predict the gene clusters which can be used in biosynthetic pathway engineering for production of novel antibiotics [48, 74]. It is imperative to periodically asses the biosafety of these organisms to avoid accidental release of synthetic bacteria generated in some of these applications To address this concern, two engineered safeguard systems called the ‘Deadman’ and ‘Passcode’ kill switches have been developed by Collins and colleagues in E. coli [77].
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