Contact

  • Academic
    mtuncel@stanford.edu
    University - Student Department: Microbiology and Immunology Position: Graduate

Additional Info

  • Mail Code: 5124

All Publications

  • An unusual genetic switch controls Mycobacterium avium pathogenesis, antibiotic resistance and colony morphology. bioRxiv : the preprint server for biology Nilsson, H. J., Netter, Z., Tuncel, M., Garelis, N. E., Siddiqui, N., Semaan, M., McCall, R. M., Dangerfield, K., Cox, E. K., Britt, L., Voorhies, M., Roberts, A. W., Mitchell, G., Cangelosi, G. A., Jacobs, W. R., Sil, A., Budzik, J. M., Cox, J. S. 2025

    Abstract

    Mycobacterium avium subspecies hominissuis (Mah) is an emerging environmental pathogen highly adapted to a wide range of niches, from treated water systems to mammalian tissues. On solid media, Mah forms two distinct colony morphologies, smooth transparent (SmT) and smooth opaque (SmO). These colony morphologies are representative of broader differential phenotypic states in which SmT cells are virulent and have high resistance to antibiotics while SmO cells are avirulent, antibiotic-sensitive and grow faster than SmT cells in culture. Importantly, Mah interconverts between these two morphotypes but the mechanism of SmT-SmO switching is unknown. Here we show that SmT-SmO switching is governed by a reversible transposition event that regulates expression of a periplasmic lipoprotein, Erp (extracellular repetitive protein). We found that transposition of IS1245, an endogenous insertion sequence, into the erp gene correlated with the SmT-SmO transition, and its precise removal coincided with the switch back to SmT. Genetic analyses showed that erp is required for maintenance of the SmT state and sufficient to drive the switch from SmO to SmT. We also identified a mutation in a periplasmic protease, MarP, that locks Mah in the SmO state and blocks erp-mediated switching to SmT. Our results indicate that Erp and MarP function in a signal transduction pathway that regulates a broad transcriptional response to periplasmic stress. Moreover, identification of components that control Mah colony morphology switching has revealed a potential new strategy for combating the inherent antibiotic resistance of Mycobacterium avium infections.

    View details for DOI 10.1101/2025.07.28.667291

    View details for PubMedID 40766380

    View details for PubMedCentralID PMC12324328

  • High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection. Nature genetics Wang, B. X., Leshchiner, D., Luo, L., Tuncel, M., Hokamp, K., Hinton, J. C., Monack, D. M. 2024

    Abstract

    Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi and Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.

    View details for DOI 10.1038/s41588-024-01779-7

    View details for PubMedID 38831009

    View details for PubMedCentralID 10023398