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Taddei, S.

Publications and source records attributed to Taddei, S..

2 recordsLinked to original sources

Generation, characterization and exploiting caprine herpesvirus 1 secreted glycoprotein D

Caprine herpesvirus 1 (CpHV-1), a member of the Herpesvirales order, Herpesviridae family, Alphaherpesvirinae subfamily, and Simplexvirus genus, is classically associated to two distinct clinical syndromes. In kids, CpHV-1 induces severe systemic disease with high morbidity and mortality, in adult goats, the infection leads to genital lesions such as vulvovaginitis or balanoposthitis, with abortions occurring mainly in the second half of gestation. CpHV-1 shares several biological characteristics with human herpesvirus 2 (HSV-2), including molecular features, tropism for vaginal epithelium, genital lesion nature and latency in the sacral ganglia. These features make CpHV-1-infected goats a reliable animal model for studying human herpesvirus-induced genital disease, employable for pathogenic research, as well as the development of new vaccines and antiviral agents. Recent full sequencing of CpHV-1 genome has identified at least ten genes encoding glycoproteins. Among these, glycoprotein D (gD) has been characterized but not yet exploited for immunogenic or diagnostic purposes. In this study, the structural features of CpHV-1 gD were predicted using in silico analysis. A truncated version of gD lacking the transmembrane domain (Sec-gD) was subsequently generated and expressed in mammalian cells, enabling its secretion into the culture medium. Despite the structural modifications, Sec-gD retained a conserved glycosylation pattern, as confirmed by PNGase F treatment. Furthermore, the antigenic properties of Sec-gD were preserved, as demonstrated by reverse serum neutralization assays. Notably, the culture supernatant containing Sec-gD was directly usable in diagnostic enzyme-linked immunosorbent assays, supporting its potential as a valuable tool for both diagnostic and immunization strategies. ImportanceCpHV-1-infected goats represent a large animal model for studying human herpesvirus-induced genital disease, and could be utilized for pathogenic research, as well as for the development of new vaccines and antiviral agents. CpHV-1 gD can be efficiently produced and rescued from the supernatant of transfected mammalian cells, retaining its immunogenic properties and could be employed for immunogenic and diagnostic purposes.

microbiology↗

Preferential catabolism of L- vs D-serine by Proteus mirabilis contributes to pathogenesis and catheter-associated urinary tract infection

Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter-associated urinary tract infection (CAUTI), particularly D- and L-serine. In this study, we sought to determine the hierarchy of amino acid utilization by P. mirabilis and to examine the relative importance of D- vs L-serine catabolism for critical steps in CAUTI development and progression. Herein, we show that P. mirabilis preferentially catabolizes L-serine during growth in human urine, followed by D-serine, threonine, tyrosine, glutamine, tryptophan, and phenylalanine. Independently disrupting catabolism of either D- or L-serine has minimal impact on in vitro phenotypes while completely disrupting both pathways decreases motility, biofilm formation, and fitness due to perturbation of membrane potential and cell wall biosynthesis. In a mouse model of CAUTI, loss of either serine catabolism system decreased fitness, but disrupting L-serine catabolism caused a greater fitness defect than disrupting D-serine catabolism. We therefore conclude that hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract. Abbreviated SummaryAmino acids are a predominant nutrient in urine, and their import and catabolism has been hypothesized to contribute to the ability of bacteria to cause urinary tract infection. We demonstrate that a common uropathogen, Proteus mirabilis, preferentially catabolizes L-serine followed by D-serine, threonine, tyrosine, and glutamine during growth in human urine. We further demonstrate that L-serine catabolism provides a greater fitness advantage than D-serine catabolism, yet both pathways contribute to pathogenesis in the urinary tract. Graphical Abstract(Created using BioRender.com) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/494593v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@13f3286org.highwire.dtl.DTLVardef@e0e84org.highwire.dtl.DTLVardef@db2946org.highwire.dtl.DTLVardef@72b421_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗