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Pastore, G.

Publications and source records attributed to Pastore, G..

2 recordsLinked to original sources

Streptococcus pyogenes Φ1207.3 is a temperate bacteriophage carrying the macrolide efflux gene pair mef(A)-msr(D) and capable to lysogenise different Streptococci

Streptococcus pyogenes prophage {phi}1207.3 (formerly Tn1207.3) carries the mef(A)-msr(D) efflux resistance genes, responsible for type M macrolide resistance. To investigate if {phi}1207.3 is a functional bacteriophage, we transferred the element from the original S. pyogenes host in a prophage-free and competence-deficient S. pneumoniae strain. Pneumococcal cultures of the {phi}1207.3-carrying lysogen were treated with mitomycin C to assess if {phi}1207.3 enters the lytic cycle. Mitomycin C induced a limited phage burst and a growth impairment resulting in early entrance in the stationary phase. To determine if {phi}1207.3 is able to produce mature phage particles we prepared concentrated supernatants recovered from a mitomycin C induced pneumococcal culture by sequential centrifugation and ultracentrifugation steps. Negative staining Transmission Electron Microscopy (TEM) of supernatants revealed the presence of phage particles with an icosahedral, electron dense capsid and a long, non-contractile tail, typical of a siphovirus. Quantification of {phi}1207.3 was performed by qPCR and semi-quantitatively by TEM. PCR quantified 3.34 x 104 and 6.06 x 104 excised forms of phage genome per ml of supernatant obtained from the untreated and mitomycin C treated cultures, respectively. By TEM, we estimated 3.02 x 103 and 7.68 x 103 phage particles per ml of supernatant. The phage preparations of {phi}1207.3 infected and lysogenised pneumococcal recipient strains at a frequency of 7.5 x 10-6 lysogens/recipient, but did not show sufficient lytic activity to form plaques. Phage lysogenisation efficiently occurred after 30 minutes of contact of the phages with the recipient cells and required a minimum of 103 phage particles. ImportanceBacteriophages play an important role in bacterial physiology and genome evolution. The widespread use of genome sequencing revealed that bacterial genomes can contain several different integrated temperate bacteriophages, which can constitute up to 20% of the genome. Most of these bacteriophages are only predicted in silico and never shown to be functional. In fact, it is often difficult to induce the lytic cycle of temperate bacteriophages. In this work, we show that {phi}1207.3, a peculiar bacteriophage originally from Streptococcus pyogenes, which can lysogenise different Streptococci and carries the macrolide resistance mef(A)-msr(D) gene pair, is capable of producing mature virions, but only at a low level, while not being able to produce plaques. This temperate phage is probably a partially functional phage, which seems to have lost lytic characteristics to specialize into lysogenisation. While we are not used to conceive phages separately from lysis, this behavior could actually be more frequent than expected.

microbiology↗

Interaction with C21ORF2 controls the cellular functions of the NEK1 kinase

NEK1 is a pleiotropic protein kinase implicated in mitosis, ciliogenesis and DNA repair but little is known about its regulation or targets. Its relevance for human health is underscored by the association of NEK1 mutations with human diseases including axial spondylometaphyseal dyplasia (SMD) and amyotrophic lateral sclerosis (ALS). Mutations in the C21ORF2 gene are associated with a similar pattern of human diseases, suggesting close functional links with NEK1. Here we report that in unperturbed, untransformed cells, endogenous NEK1 and C21ORF2 form a tight complex that does not appear to contain other proteins. A small acidic domain "CID: C21ORF2 interaction domain" at the C-terminus of NEK1 is necessary and sufficient to interact with C21ORF2, and pathogenic mutations in this region disrupt the complex. AlphaFold modelling predicts with high confidence an extended binding interface between a leucine-rich repeat (LRR) domain in the N-terminal half of C21ORF2 and a stretch of the NEK1-CID; mutating residues mediating electrostatic interactions within this interface disrupts the NEK1-C21ORF2 interaction. This model also explains why pathogenic mutations disrupt the complex. We go on to show that the kinase activity of NEK1 and its interaction with C21ORF2 is critical for NEK1 function in cells. These data reveal C21ORF2 as a regulatory subunit of NEK1, illuminating our understanding of how this kinase is regulated and NEK1-C21ORF2-associated diseases.

biochemistry↗