Infection remains a major cause of morbidity, mortality and technique failure in patients with end stage kidney failure who receive peritoneal dialysis (PD). Recent research suggests that the early inflammatory response at the site of infection carries diagnostically relevant information, suggesting that organ and pathogen-specific “immune fingerprints” may guide targeted treatment decisions and allow patient stratification and risk prediction at the point of care. Here, we recorded microRNA profiles in the PD effluent of patients presenting with symptoms of acute peritonitis and show that elevated peritoneal miR-223 and reduced miR-31 levels were useful predictors of bacterial infection. Cell culture experiments indicated that miR-223 was predominantly produced by infiltrating immune cells (neutrophils, monocytes), while miR-31 was mainly derived from the local tissue (mesothelial cells, fibroblasts). miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Our study demonstrates that microRNAs are useful biomarkers of bacterial infection in PD-related peritonitis and have the potential to contribute to disease-specific immune fingerprints. Exosome-encapsulated microRNAs may have a functional role in intercellular communication between immune cells responding to the infection and the local tissue, to help clear the infection, resolve the inflammation and restore homeostasis.

/pdf/neutrophil-derived-mir-223-as-local-biomarker-of-bacterial-ho9jfb4h5x.pdf

Neutrophil-derived miR-223 as local biomarker of bacterial peritonitis

Many bacterial and archaeal lineages have a history of extensive and ongoing horizontal gene transfer and loss, as evidenced by the large differences in genome content even among otherwise closely related isolates. How ecologically cohesive populations might evolve and be maintained under such conditions of rapid gene turnover has remained controversial. Here we synthesize recent literature demonstrating the importance of habitat and niche in structuring horizontal gene transfer. This leads to a model of ecological speciation via gradual genetic isolation triggered by differential habitat-association of nascent populations. Further, we hypothesize that subpopulations can evolve through local gene-exchange networks by tapping into a gene pool that is adaptive towards local, continuously changing organismic interactions and is, to a large degree, responsible for the observed rapid gene turnover. Overall, these insights help to explain how bacteria and archaea form populations that display both ecological cohesion and high genomic diversity.

Horizontal gene transfer and the evolution of bacterial and archaeal population structure

Antimicrobial resistance is a global threat to human health and welfare, food safety, and environmental health. The rapid detection and quantification of antimicrobial resistance are important for both infectious disease control and public health threat assessment. Technologies such as flow cytometry can provide clinicians with the early information, they need for appropriate antibiotic treatment. At the same time, cytometry platforms facilitate the measurement of antibiotic-resistant bacteria in environments impacted by human activities, enabling assessment of their impact on watersheds and soils. This review focuses on the latest applications of flow cytometry for the detection of pathogens and antibiotic-resistant bacteria in both clinical and environmental samples. Novel antimicrobial susceptibility testing frameworks embedding flow cytometry assays can contribute to the implementation of global antimicrobial resistance surveillance systems that are needed for science-based decisions and actions. 

/pdf/current-and-future-flow-cytometry-applications-contributing-26dq0aq3.pdf

Current and Future Flow Cytometry Applications Contributing to Antimicrobial Resistance Control

Peritoneal dialysis (PD) is a cost-effective, home-based treatment option for patients with end-stage renal disease; however, PD is declining in many countries. A major reason for this is peritonitis, which commonly leads to technique failure and has led to negative perceptions of PD by clinicians and patients. To restore confidence in PD, better diagnostics are required to enable appropriate treatment to be started earlier; this needs to be coupled with improved understanding of the biology of peritonitis. Advances in culture-independent microbiological methods, in particular the use of bacterial flow cytometry and immune fingerprinting techniques, can enable organism detection and antimicrobial susceptibility testing to be performed in as little as 3 hours after samples are received. At the same time, improved understanding of peritoneal mesothelial cell responses to infection is providing insights into pathways that may be targeted to dampen deleterious elementsof the host immune response, promote healing, and preserve membrane function.

Peritonitis in Peritoneal Dialysis patients: the case for rapid diagnosis, targeted treatment and monitoring to improve outcomes

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Peritonitis in Peritoneal Dialysis patients: the case for rapid diagnosis, targeted treatment and monitoring to improve outcomes