Systematic identification of hypothetical bacteriophage proteins targeting key protein complexes of Pseudomonas aeruginosa

An Van Den Bossche, Pieter Jan Ceyssens, Jeroen De Smet, Hanne Hendrix, Hannelore Bellon, Nadja Leimer, Jeroen Wagemans, Anne Sophie Delattre, William Cenens, Abram Aertsen, Bart Landuyt, Leonid Minakhin, Konstantin Severinov, Jean Paul Noben, Rob Lavigne

Результат исследований: Вклад в журналСтатьярецензирование

42 Цитирования (Scopus)

Аннотация

Addressing the functionality of predicted genes remains an enormous challenge in the postgenomic era. A prime example of genes lacking functional assignments are the poorly conserved, early expressed genes of lytic bacteriophages, whose products are involved in the subversion of the host metabolism. In this study, we focused on the composition of important macromolecular complexes of Pseudomonas aeruginosa involved in transcription, DNA replication, fatty acid biosynthesis, RNA regulation, energy metabolism, and cell division during infection with members of seven distinct clades of lytic phages. Using affinity purifications of these host protein complexes coupled to mass spectrometric analyses, 37 host complex-associated phage proteins could be identified. Importantly, eight of these show an inhibitory effect on bacterial growth upon episomal expression, suggesting that these phage proteins are potentially involved in hijacking the host complexes. Using complementary protein-protein interaction assays, we further mapped the inhibitory interaction of gp12 of phage 14-1 to the α subunit of the RNA polymerase. Together, our data demonstrate the powerful use of interactomics to unravel the biological role of hypothetical phage proteins, which constitute an enormous untapped source of novel antibacterial proteins. (Data are available via ProteomeXchange with identifier PXD001199.)

Язык оригиналаАнглийский
Страницы (с-по)4446-4456
Число страниц11
ЖурналJournal of Proteome Research
Том13
Номер выпуска10
DOI
СостояниеОпубликовано - 3 окт. 2014
Опубликовано для внешнего пользованияДа

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