Invention Description
Antibiotic-resistant nontuberculous mycobacteria (NTM) infections are increasing at ~8% annually, placing a significant burden on healthcare systems. Mycobacterium abscessus (Mabs) represents one of the most treatment-refractory pathogens, particularly in cystic fibrosis (CF) patients. Mabs disease severity is strongly associated with morphotypic conversion from smooth to rough variants, yet current models cannot dynamically and reversibly simulate this transition. Biological signals associated with the permanent genetic changes that induce this conversion remain poorly understood, limiting progress toward morphotype-specific therapeutic targets.
Researchers at Arizona State University have developed a CRISPR interference (CRISPRi)-based molecular toolbox system that enables precise, reversible switching between smooth and rough Mabs morphotypes, allowing for dynamic simulation of infection processes and morphotype-specific responses. This system achieves high conversion (100%) efficiency in inducing rough morphotype conversion without permanent genomic alteration, allowing dynamic modeling of infection states in vitro and in animal models. The platform enables preclinical research, morphotype-specific therapeutic testing, and improved modeling of pulmonary disease progression, and enhanced study of host-pathogen interactions relevant to antibiotic-resistant NTM infections.
Potential Applications
- Preclinical infectious disease research and drug discovery
- Morphotype-specific testing
- Host-pathogen interaction and bacterial pathogenesis studies
- Development of antimicrobials targeting morphotype-specific vulnerabilities
- Animal modeling of NTM infections
- Development of therapeutics targeting CF-associated infections
Benefits and Advantages
- Reversible control of bacterial morphotypes without permanent genetic changes
- Efficient and complete induction of rough morphotype switching
- Dynamic modeling of infection states and infection progression
- Improved preclinical predictive power
- Enhanced host-pathogen interaction analyses
- Enables in-depth study of Mabs pathophysiology
- Potential to improve treatment strategies for antibiotic-resistant infections
- Versatile tool for preclinical drug testing and pathogenesis studies
- Applicable to pulmonary and CF-associated infection models