Bacterial genome engineering and synthetic biology: combating pathogens.
The 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.



The 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.



The 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.
Department of Target Discovery and Experimental Microbiology, Division of Molecular and Translational Sciences, U. S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, 21702, USA.
Malathy
0000-0001-6442-7247
M
Krishnamurthy
Department of Target Discovery and Experimental Microbiology, Division of Molecular and Translational Sciences, U. S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, 21702, USA.
Richard T
RT
Moore
Department of Target Discovery and Experimental Microbiology, Division of Molecular and Translational Sciences, U. S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, 21702, USA.
Sathish
S
Rajamani
Department of Target Discovery and Experimental Microbiology, Division of Molecular and Translational Sciences, U. S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, 21702, USA. rekha.g.panchal.civ@mail.mil.
Rekha G
RG
Panchal
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000235:genetics* / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D016503:Drug Delivery Systems; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics / Q000502:physiology; D053263:Gene Regulatory Networks; D005818:Genetic Engineering; D016680:Genome, Bacterial; D006801:Humans; D000071059:Phage Therapy; D015995:Prevalence; D053038:Quorum Sensing; D012329:RNA, Bacterial; D011995:Recombination, Genetic; D058615:Synthetic Biology / Q000295:instrumentation* / Q000379:methods*; D014774:Virulence
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial
Antibacterial; Antibiotic resistance; Gene circuits; Genome engineering; Multidrug resistant (MDR) pathogens; Pathogenesis; Quorum sensing; Recombineering; Synthetic Biology (SB); Targetron