Antenatal ureaplasma infection causes colonic mucus barrier defects: implications for intestinal pathologies

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development

Hypervirulent Clostridium difficile PCR-Ribotypes Exhibit Resistance to Widely Used Disinfectants

The increased prevalence of Clostridium difficile infection (CDI) has coincided with enhanced transmissibility and severity of disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 and 017 responsible for CDI outbreaks in the USA, Europe and Asia. We assessed sporulation and susceptibility of three PCR-ribotypes; 012, 017 and 027 to four classes of disinfectants; chlorine releasing agents (CRAs), peroxygens, quaternary ammonium compounds (QAC) and biguanides. The 017 PCR-ribotype, showed the highest sporulation frequency under these test conditions. The oxidizing biocides and CRAs were the most efficacious in decontamination of C. difficile vegetative cells and spores, the efficacy of the CRAs were concentration dependent irrespective of PCR-ribotype. However, there were differences observed in the susceptibility of the PCR-ribotypes, independent of the concentrations tested for Virkon®, Newgenn®, Proceine 40® and Hibiscrub®. Whereas, for Steri7® and Biocleanse® the difference observed between the disinfectants were dependent on both PCR-ribotype and concentration. The oxidizing agent Perasafe® was consistently efficacious across all three PCR ribotypes at varying concentrations; with a consistent five Log10 reduction in spore titre. The PCR-ribotype and concentration dependent differences in the efficacy of the disinfectants in this study indicate that disinfectant choice is a factor for llimiting the survival and transmission of C. difficile spores in healthcare settings

Pathoadaptive mutations of Escherichia coli K1 in experimental neonatal systemic infection

Although Escherichia coli K1 strains are benign commensals in adults, their acquisition at birth by the newborn may result in life-threatening systemic infections, most commonly sepsis and meningitis. Key features of these infections, including stable gastrointestinal (GI) colonization and age-dependent invasion of the bloodstream, can be replicated in the neonatal rat. We previously increased the capacity of a septicemia isolate of E. coli K1 to elicit systemic infection following colonization of the small intestine by serial passage through two-day-old (P2) rat pups. The passaged strain, A192PP (belonging to sequence type 95), induces lethal infection in all pups fed 2–6 x 106 CFU. Here we use whole-genome sequencing to identify mutations responsible for the threefold increase in lethality between the initial clinical isolate and the passaged derivative. Only four single nucleotide polymorphisms (SNPs), in genes (gloB, yjgV, tdcE) or promoters (thrA) involved in metabolic functions, were found: no changes were detected in genes encoding virulence determinants associated with the invasive potential of E. coli K1. The passaged strain differed in carbon source utilization in comparison to the clinical isolate, most notably its inability to metabolize glucose for growth. Deletion of each of the four genes from the E. coli A192PP chromosome altered the proteome, reduced the number of colonizing bacteria in the small intestine and increased the number of P2 survivors. This work indicates that changes in metabolic potential lead to increased colonization of the neonatal GI tract, increasing the potential for translocation across the GI epithelium into the systemic circulation

Functional mucous layer and healing of proximal colonic anastomoses in an experimental model

Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. Of 22 Muc2-deficient (Muc2(-/-) ) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2(-/-) mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2(-/-) mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2(-/-) mice compared with controls (P = 0·011). A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recover

Benthos distribution modelling and its relevance for marine ecosystem management

Marine benthic ecosystems are difficult to monitor and assess, which is in contrast to modern ecosystem-based management requiring detailed information at all important ecological and anthropogenic impact levels. Ecosystem management needs to ensure a sustainable exploitation of marine resources as well as the protection of sensitive habitats, taking account of potential multiple-use conflicts and impacts over large spatial scales. The urgent need for large-scale spatial data on benthic species and communities resulted in an increasing application of distribution modelling (DM). The use of DM techniques enables to employ full spatial coverage data of environmental variables to predict benthic spatial distribution patterns. Especially, statistical DMs have opened new possibilities for ecosystem management applications, since they are straightforward and the outputs are easy to interpret and communicate. Mechanistic modelling techniques, targeting the fundamental niche of species, and Bayesian belief networks are the most promising to further improve DM performance in the marine realm. There are many actual and potential management applications of DMs in the marine benthic environment, these are (i) early warning systems for species invasion and pest control, (ii) to assess distribution probabilities of species to be protected, (iii) uses in monitoring design and spatial management frameworks (e.g. MPA designations), and (iv) establishing long-term ecosystem management measures (accounting for future climate-driven changes in the ecosystem). It is important to acknowledge also the limitations associated with DM applications in a marine management context as well as considering new areas for future DM developments. The knowledge of explanatory variables, for example, setting the basis for DM, will continue to be further developed: this includes both the abiotic (natural and anthropogenic) and the more pressing biotic (e.g. species interactions) aspects of the ecosystem. While the response variables on the other hand are often focused on species presence and some work undertaken on species abundances, it is equally important to consider, e.g. biological traits or benthic ecosystem functions in DM applications. Tools such as DMs are suitable to forecast the possible effects of climate change on benthic species distribution patterns and hence could help to steer present-day ecosystem management

Supporting the Essential - Recommendations for the Development of Accessible and Interoperable Marine Biological Data Products

In this paper we outline the stakeholder-led approaches in the development of biological data products to support effective conservation, management and policy development. The requirements of a broad range of stakeholders and iterative, structured processes framed the development of tools, models and maps that support the FAIR (Findable, Accessible, Interoperable, Reusable) data principles. By structuring the resultant data products around the emerging biological Essential Ocean Variables, and through the engagement with a broad range of end-users, the EMODnet (European Marine Observation and Data Network) Biology project has delivered a suite of demonstration data products. These products are presented in the European Atlas of Marine Life, an online resource demonstrating the value of open marine biodiversity data and help to answer fundamental and policy-driven questions related to managing the natural and anthropogenic impacts in European waters

Responses of marine benthos to climate change

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