Bacterial genome engineering and synthetic biology: combating pathogens

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.

Study of the Antimicrobial Activity of Tilapia Piscidin 3 (TP3) and TP4 and Their Effects on Immune Functions in Hybrid Tilapia (Oreochromis spp.)

“…Previous publications have reported a lack of regulation and enforcement of antibiotic use among aquaculture farmers in developing countries [11]. The misuse of antibiotics as prophylactic agents to prevent disease has given rise to the development of antibiotic resistance [19]. TP3 and TP4 exert biological effects against microbes, which indicates that they are potent and promising antimicrobial agents with a broad spectrum of activities [1].…”

Antibiyotiklere Alternatif Terapi: CRISPR-Cas antimikrobiyalleri

“…To overcome the problem of the antimicrobial resistance, there has been developed new therapeutic solutions including new schemes of antivirulence strategies, bacteriophage therapies, probiotics, therapeutic antibodies, synthetic inhibitor drugs specifically inhibiting resistance enzymes, bacterial efflux pumps, biofilm formation, fatty acid biosynthesis pathway, cell division, and amino acid metabolism in the antibiotic-resistant bacteria (Schimmel et al, 1998;Su and Honek, 2007;Lock and Harry, 2008;Lu and Collinsi, 2009;Njoroge and Sperandio, 2009;Kohanski et al, 2010). Bacterial genome modification techniques have also the potential to combat the infectious diseases (Krishnamurthy et al, 2016). Indeed, several programmable nuclease approaches such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs) have been developed in studies for twenty years.…”

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