Biology subjects

Venturini, C.

Publications and source records attributed to Venturini, C..

3 recordsLinked to original sources

bioRxiv2018

Immune profiling of cord blood after prolonged rupture of membranes.

We hypothesised that foetal immune responses to an infectious challenge may be detected by genome-wide transcriptional profiling of cord blood. In order to test this hypothesis, we sought to identify transcriptomic changes in post-natal cord blood samples following prolonged pre-labour rupture of membranes (PROM) as a surrogate for increased risk of infection. By comparison to controls we found increased levels of blood transcripts in a subset of prolonged PROM cases, significantly enriched for innate immune system signalling pathways. These changes were idiosyncratic, suggesting qualitative and quantitative variation in foetal immune responses which may reflect differences in exposure and/or in host genetics. Our data support the view that PROM represents an infection risk to the foetus. In addition, we propose that cord blood transcriptional profiling offers exciting opportunities to identify immune correlates of clinical outcome following potential in utero exposures to infection. These may be used to elucidate the mechanisms of immunological protection and pathology in the foetus and identify biomarkers to stratify the risk of adverse outcomes.

immunology↗

bioRxiv2018

Whole genome analysis of ExPEC ST73 from a single hospital over a 2-year period identified different circulating clonal groups

ST73 has emerged as one of the most frequently isolated extraintestinal pathogenic E. coli (ExPEC). To examine the localised diversity of ST73 clonal groups including their mobile genetic elements profile, we sequenced the genomes of 16 multiple drug-resistant ST73 isolates from patients with urinary tract infection from a single hospital in Sydney, Australia between 2009 and 2011. Genome sequences were used to generate a SNP-based phylogenetic tree to determine the relationship of these isolates in a global context with ST73 sequences (n=210) from public databases. There was no evidence of a dominant outbreak strain of ST73 in patients from this hospital, rather we identified at least eight separate groups, several of which reoccur, over a two-year period. The inferred phylogeny of all ST73 strains (n=226) including the ST73 Clone D i2 reference genome shows high bootstrap support and clusters into four major groups which correlate with serotype. The Sydney ST73 strains carry a wide variety of virulence-associated genes but the presence of iss, pic and several iron acquisition operons was notable.\n\nImpactST73 is a major clonal lineage of ExPEC that causes urinary tract infections often with uroseptic sequelae but has not garnered substantial scientific interest as the globally disseminated ST131. Isolation of multiple antimicrobial resistant variants of ExPEC ST73 have increased in frequency, but little is known about the carriage of class 1 integrons in this sequence type and the plasmids that are likely to mobilise them. This pilot study examines the ST73 isolates within a single hospital in Sydney Australia and provides the first large-scale core-genome phylogenetic analysis of ST73 utilizing public sequence read datasets. We used this analysis to identify at least 8 sub-groups of ST73 within this single hospital. Mobile genetic elements associated with antibiotic resistance were less diverse and only three class 1 integron structures were identified, all sharing the same basic structure suggesting that the acquisition of drug resistance is a recent event. Genomic epidemiological studies are needed to further characterise established and emerging clonal populations of multiple drug resistant ExPEC to identify sources and aid outbreak investigations.

genomics↗

bioRxiv2018

Epithelial control of colonisation by Streptococcus pneumoniae at the human mucosal surface

Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive disease, interrupting onward transmission, and in achieving herd protection. We hypothesised that the pattern of pneumococcal-epithelial engagement dictates the inflammatory response to colonisation, and that this epithelial sensing is linked to bacterial clearance. Here we have used nasal curette biopsies from a serotype 6B Experimental Human Pneumococcal Carriage Model (EHPC) to visualize S. pneumoniae colonisation and relate these interactions to epithelial surface marker expression and transcriptomic profile upregulation. We have used a Detroit 562 cell co-culture model to further understand these processes and develop an integrated epithelial transcriptomic module to interrogate gene expression in the EHPC model. We have shown for the first time that pneumococcal colonisation in humans is characterised by microcolony formation at the epithelial surface, microinvasion, cell junction protein association, epithelial sensing, and both epithelial endocytosis and paracellular transmigration. Comparisons with other clinical strains in vitro has revealed that the degree of pneumococcal epithelial surface adherence and microinvasion determines the host cell surface marker expression (ICAM-1 and CD107), cytokine production (IL-6, IL-8 and ICAM-1) and the transcriptomic response. In the context of retained barrier function, epithelial microinvasion is associated with the upregulation of a wide range of epithelial innate signalling and regulatory pathways, inflammatory mediators, adhesion molecules, cellular metabolism and stress response genes. The prominence of epithelial TLR4R signalling pathways implicates pneumolysin, a key virulence factor, but although pneumolysin gene deletion partially ameliorates the inflammatory transcriptional response in vitro, critical inflammatory pathways persist in association with enhanced epithelial adhesion and microinvasion. Importantly, the pattern of the host-bacterial interaction seen with the 6B strain in vitro is also reflected in the EHPC model, with evidence of microinvasion and a relatively silent epithelial transcriptomic profile that becomes most prominent around the time of bacterial clearance. Together these data suggest that epithelial sensing of the pneumococcus during colonisation in humans is enhanced by microinvasion, resulting in innate epithelial responses that are associated with bacterial clearance.\n\nHighlights\n\nO_LIColonisation of the human mucosa by Streptococcus pneumoniae is associated with microcolony formation, microinvasion, epithelial sensing and an epithelial innate response.\nC_LIO_LIFollowing adherence to the epithelial cell surface, microinvasion of the epithelium may occur by endocytosis and/or lateral migration between cells without necessarily compromising barrier integrity.\nC_LIO_LIThe pattern of pneumococcal epithelial surface adherence and microinvasion determines the host cell response through a range of innate signaling and regulatory pathways, inflammatory mediators, adhesion molecules, cellular metabolism and stress response genes.\nC_LIO_LIEpithelial sensing is triggered by, but not wholly dependent on pneumolysin, a key virulence factor of S. pneumoniae.\nC_LI

immunology↗