Loss of PmpC in Chlamydia trachomatis leads to altered bacterial development and impaired recovery from IFNγ- and penicillin-induced stress

@article{anna2026loss,
  title = {{Loss of PmpC in Chlamydia trachomatis leads to altered bacterial development and impaired recovery from IFNγ- and penicillin-induced stress}},
  author = {Ailen N. Anna and María E. Panzetta and Gloria N. Bettucci Ferrero and Constanza Marín and Belkys A. Maletto and Diego D. del Balzo and Mariano Alonso Bivou and Maria T. Damiani and Robert J. Bastidas and Raphael H. Valdivia and Héctor A. Saka},
  journal = {Microbiology Spectrum},
  year = {2026},
  month = oct,
  doi = {10.1128/spectrum.01773-26},
  url = {https://doi.org/10.1128/spectrum.01773-26},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Loss of PmpC in Chlamydia trachomatis leads to altered bacterial development and impaired recovery from IFNγ- and penicillin-induced stress
AU  - Ailen N. Anna
AU  - María E. Panzetta
AU  - Gloria N. Bettucci Ferrero
AU  - Constanza Marín
AU  - Belkys A. Maletto
AU  - Diego D. del Balzo
AU  - Mariano Alonso Bivou
AU  - Maria T. Damiani
AU  - Robert J. Bastidas
AU  - Raphael H. Valdivia
AU  - Héctor A. Saka
PY  - 2026
DA  - 2026/10/12
JO  - Microbiology Spectrum
DO  - 10.1128/spectrum.01773-26
UR  - https://doi.org/10.1128/spectrum.01773-26
AB  - Chlamydia trachomatis is an obligate intracellular pathogen that can reversibly halt replication and developmental transitions in response to immunological or pharmacological stress, a phenomenon linked to chlamydial persistence. Although polymorphic membrane proteins (Pmps) are known adhesins, their broader roles in other pathogenesis-relevant processes remain poorly understood. Here, we characterized a pmpC-null mutant generated by insertional mutagenesis and found that while PmpC is not essential for primary growth, it is required for the efficient transition from reticulate bodies to infectious elementary bodies during recovery from IFNγ- and penicillin-induced stress. High-resolution microscopy and temporal expression analysis revealed that PmpC localizes to the bacterial periphery throughout the developmental cycle and is released into the lumen of pathogen-containing vacuoles (inclusions), suggesting a role beyond bacterial attachment to host cells. The absence of PmpC leads to clustered bacterial distribution and reduced bacterial mobility within the inclusion. These defects correlate with delayed cellular invasion and impaired dissemination to adjacent host cells. Notably, the significance of PmpC in penicillin-induced persistence was validated using an ex vivo murine uterine horn model. Altogether, our findings reveal PmpC as a multifunctional virulence factor that mediates stress recovery, regulates bacterial distribution and dynamics within the inclusion, modulates early invasion and facilitates lateral spread, expanding its recognized role as an adhesin.  IMPORTANCE: Chlamydia trachomatis is a leading cause of sexually transmitted infections and preventable blindness globally. A significant challenge in controlling chlamydial diseases is the ability of these bacteria to enter a reversibly non-replicating “persistent” state to survive immune pressure, nutritional stress, or antibiotic treatment. In this study, we identify the surface protein PmpC as a multifunctional factor required for bacterial recovery from IFNγ- and penicillin-induced stress, in both tissue culture and an ex vivo murine model of uterine infection. Furthermore, we found that PmpC modulates invasion and bacterial spatial distribution within the inclusion. These findings uncover novel roles for PmpC as a virulence factor in C. trachomatis infection.
SN  - 2165-0497
ER  -