Proteome analysis of Bordetella pertussis isolated from human macrophages

YANINA LAMBERTI; JUAN HILARIO CAFIER; KRISTIN SURMANN; HUGO VALDEZ; JANA HOLUBOVA; BRANISLAV VECEREK; PETER SEBO ; FRANK SCHMIDT ; UWE VÖLKER; MARIA EUGENIA RODRIGUEZ

JOURNAL OF PROTEOMICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 136 p. 55 - 67

1874-3919

Previous studies have shown that B. pertussis survives inside human macrophages in non-acidic compartments with characteristics of early endosomes. In order to gain new insight into the biology of B. pertussis survival in host cells,we haveanalyzed the adaptationof thebacterialproteomeduring intracellular infection.The proteome of B. pertussis 3 h and 48 h after infection of human macrophage-like THP-1 cells was examined by nano-liquid chromatography combined with tandem MS and compared to the protein profile of extracellular B. pertussis growing in the same cell culture medium. Compared with extracellular bacteria, almost 300 proteins out of 762 identified proteins displayed altered levels in intracellular B. pertussis. Functional analyses of the proteins displaying altered abundance revealed enrichment of proteins involved in stress response, iron uptake, cellular metabolism, transcriptional regulation, and virulence. To our knowledge, this is the first analysis of the B. pertussis proteomeduring adaptation to the intramacrophage environment and the data provide new clues for understanding B. pertussis adaptation and pathogenesis. Biological significance: B. pertussis is a respiratory pathogen that has adapted exclusively to the human host. De- spite high vaccination rates, whooping cough remains a serious threat to human health and its incidence has been increasing in recent years in vaccinated populations. Themechanismsthat allowthis pathogen to evade im- mune clearance, persist in the host, and cause a prolonged paroxysmal cough are still poorly understood. Recent studies regarding B. pertussis survival inside host cells and the cellular response to this bacterial infection indicate that B. pertussis may have an intracellular phase during infectionwhich probably contributes to persistence and vaccine failure. In this study we provide the first global proteome profile of B. pertussiswithin macrophages. The data provide novel insights into the adaptive responses elicited by these bacteria for physiological adaptation to the host environment.