The study identifies a virulence locus (HSI-I) in *Pseudomonas aeruginosa* that encodes a protein secretion apparatus. This apparatus, which assembles in discrete subcellular locations, exports Hcp1, a hexameric protein with a 40 angstrom internal diameter. Regulatory patterns suggest that HSI-I functions during chronic infections. Hcp1 was detected in pulmonary secretions of cystic fibrosis (CF) patients and specific antibodies against Hcp1 were found in their sera, indicating a role in *P. aeruginosa* pathogenesis in CF. The authors also found that ClpV1, a ClpB-like AAA+ family protein, is a core component of the secretion apparatus and likely provides the energy for Hcp1 translocation. The study supports the development of vaccines and therapeutics targeting Hcp1 or the HSI-I-encoded apparatus to treat chronic *P. aeruginosa* infections.The study identifies a virulence locus (HSI-I) in *Pseudomonas aeruginosa* that encodes a protein secretion apparatus. This apparatus, which assembles in discrete subcellular locations, exports Hcp1, a hexameric protein with a 40 angstrom internal diameter. Regulatory patterns suggest that HSI-I functions during chronic infections. Hcp1 was detected in pulmonary secretions of cystic fibrosis (CF) patients and specific antibodies against Hcp1 were found in their sera, indicating a role in *P. aeruginosa* pathogenesis in CF. The authors also found that ClpV1, a ClpB-like AAA+ family protein, is a core component of the secretion apparatus and likely provides the energy for Hcp1 translocation. The study supports the development of vaccines and therapeutics targeting Hcp1 or the HSI-I-encoded apparatus to treat chronic *P. aeruginosa* infections.