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Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and [beta]-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes., Introduction Adverse pregnancy outcomes, including premature birth and stillbirth, are the leading causes of neonatal morbidity and mortality (1, 2). Fifteen million babies are born prematurely each year (3), and [...]

Author(s): Kristina M Adams Waldorf (corresponding author) [1]; Jennifer E Stencel-Baerenwald [2, 3]; Raj P Kapur [4, 5]; Colin Studholme [6, 7, 8]; Erica Boldenow [6, 9]; Jay Vornhagen [9, [...]

Showerheads support the development of multi-species biofilms that can be unsightly, produce malodor, and may harbor pathogens. The outer-surface spray-plates of many showerheads support visible biofilms that likely contain a mixture of bacteria from freshwater and potentially from human users. Coaggregation, a mechanism by which genetically distinct bacteria specifically recognize one another, may contribute to the retention and enrichment of different species within these biofilms. The aim of this work was to describe the bacterial composition of outer spray-plate biofilms of three domestic showerheads and to determine the intra- and inter-biofilm coaggregation ability of each culturable isolate. The bacterial composition of the three biofilms was determined by using bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) and by culturing on R2A medium. An average of 31 genera per biofilm were identified using bTEFAP and a total of 30 isolates were cultured. Even though the microbial diversity of each showerhead biofilm differed, every cultured isolate was able to coaggregate with at least one other isolate from the same or different showerhead biofilm. Promiscuous coaggregating isolates belonged to the generaBrevundimonas, Micrococcus, andLysobacter. This work suggests that coaggregation may be a common feature of showerhead biofilms. Characterization of the mechanisms mediating coaggregation, and the inter-species interactions they facilitate, may allow for novel strategies to inhibit biofilm development. [ABSTRACT FROM PUBLISHER]

Klebsiella pneumoniae is an opportunistic pathogen and an important cause of pneumonia, bacteremia, and urinary tract infection. K. pneumoniae infections are historically associated with diabetes mellitus. There is a fundamental gap in our understanding of how diabetes mellitus, specifically type 2 diabetes, influences K. pneumoniae pathogenesis. K. pneumoniae pathogenesis is a multifactorial process that often begins with gut colonization, followed by an escape from the gut to peripheral sites, leading to host damage and infection. We hypothesized that type 2 diabetes enhances K. pneumoniae pathogenesis. To test this, we used well-established mouse models of K. pneumoniae colonization and lung infection in conjunction with a mouse model of spontaneous type 2 diabetes mellitus (T2DM). We show that T2DM enhances susceptibility to both K. pneumoniae colonization and infection. The enhancement of gut colonization is dependent on T2DM-induced modulation of the gut microbiota community structure. In contrast, lung infection is exacerbated by the increased availability of amino acids in the lung, which is associated with higher levels of vascular endothelial growth factor. These data lay the foundation for mechanistic interrogation of the relationship between K. pneumoniae pathogenesis and type 2 diabetes mellitus, and explicitly establish T2DM as a risk factor for K. pneumoniae disease., Competing Interests: Competing interests All authors declare that they have no competing interests.

Group B Streptococci (GBS) are ß-hemolytic, gram-positive bacteria that are typically associated with infections in human newborns or immunocompromised adults. However, mutation in the two-component regulator CovR/S relieves repression of hemolysin, potentially increasing virulence of GBS. We report the isolation of hyperhemolytic/hyperpigmented GBS strain from an adolescent patient who presented to the University of Washington clinic with symptoms of sore throat. While the patient also tested positive for mononucleosis, a GBS strain with increased hemolysis was isolated from the throat swab obtained from the patient. As hyperhemolytic/hyperpigmented GBS strains are typically associated with mutations in the regulator CovR/CovS, we sequenced the covR/S loci in the clinical isolate. An adenine to cytosine mutation resulting in a change in amino acid coding sequence from glutamine at position 120 to proline in CovR (Q120P) was identified. Introduction of the Q120P amino acid substitution in a CovR complementation plasmid abolished complementation of a Δ covR mutant derived from the wild type GBS serotype Ia strain A909; these results confirm that the hyperhemolysis observed in the clinical isolate is due to the Q120P substitution in CovR. Antibiotic was prescribed and the patient's symptoms resolved without reported complications. This study represents the first report of the isolation of a hyperhemolytic/hyperpigmented GBS strain due to a covR/S mutation from an adolescent patient with persistent sore throat who was also diagnosed with mononucleosis. The isolation of GBS CovR/S mutants indicates their presence in settings of co-infections and includes adolescents.