Lipopeptide biosurfactant viscosin enhances dispersal of <i>Pseudomonas fluorescens</i> SBW25 biofilms

Pseudomonads produce several lipopeptide biosurfactants that have antimicrobial properties, but also facilitate surface motility and influence biofilm formation. Detailed studies addressing the significance of lipopeptides for biofilm formation and architecture are rare. Hence the current study sets out to determine the specific role of the lipopeptide viscosin for Pseudomonas fluorescens SBW25 biofilm formation, architecture and dispersal, and to relate viscA gene expression with viscosin production and effect. Initially, we compared biofilm formation of SBW25 and the viscosin-deficient mutant strain SBW25ΔviscA in static microtiter assays. These experiments demonstrated that viscosin had little influence on the amount of biofilm formed by SBW25 during the early stages of biofilm development. Later, however, SBW25 formed significantly less biofilm than SBW25ΔviscA. The indication that viscosin is involved in biofilm dispersal was confirmed by chemical complementation of the mutant biofilm. Further, a fluorescent bioreporter showed that viscA expression was induced in biofilms 4 hours prior to dispersal. Subsequent detailed studies of biofilms formed in flow-cells for up to 5 days revealed that SBW25 and SBW25ΔviscA developed comparable biofilms dominated by well-defined mushroom-shaped structures. Carbon-starvation was required to obtain biofilm dispersal in this system. Dispersal of SBW25 biofilms was significantly larger than of SBW25ΔviscA biofilms after 3 hours, and importantly, carbon-starvation strongly induced viscA expression, in particular for cells that were apparently leaving the biofilm. Hence the current study points towards a role for viscosin-facilitated motility in dispersal of SBW25 biofilms

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy

Background:Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. Methods: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. Results:In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69–2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1–7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 μg/mL (range 0.005–0.12 μg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4–6.9] μg/mL) and without (3.1 [range 0.7–11.0] μg/mL) infections during the first year of life (P = .41). Conclusions: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.</p