Phenotypic and transcriptomic characterization of two newly described Mycobacterium species within the Mycobacterium gordonae complex

Introduction Non-tuberculous mycobacteria constitute a rapidly emerging class of opportunistic pathogens with escalating clinical significance globally. We recently characterized two novel species within the Mycobacterium gordonae complex-Mycobacterium camsae and Mycobacterium pumcae-both isolated from human cutaneous infections. Methods Comprehensive phenotypic and transcriptomic analyses were conducted to elucidate their pathobiological properties. Comparative analysis included M. gordonae (closest phylogenetic relative), M. marinum (slow-growing reference), and M. abscessus (rapid-growing reference). Growth kinetics, intracellular survival, cytokine induction, and bacterial and host transcriptomic profiling were characterized. Results Both novel species exhibited attenuated growth kinetics characteristic of the M. gordonae complex. Notably, M. pumcae demonstrated enhanced inflammatory potential resembling M. marinum , while M. camsae displayed more subdued host responses akin to M. gordonae . Bacterial transcriptomic profiling unveiled distinct adaptive strategies: M. pumcae preferentially upregulated stress response regulons and iron homeostasis pathways, whereas M. camsae emphasized cell envelope biosynthesis and core metabolic reconfiguration. Host transcriptomic analysis at 24 h post-infection revealed differential temporal dynamics: the rapid-growing M. abscessus predominantly triggered immunometabolic reprogramming pathways, while slow-growing mycobacteria ( M. camsae, M. pumcae , and M. gordonae ) were still eliciting robust innate immune recognition signatures. Discussion This investigation provides the first systematic characterization of host-pathogen interactions within these newly described M. gordonae complex members, establishing a mechanistic foundation for understanding their distinct pathogenic trajectories and informing species-specific diagnostic and therapeutic approaches.