CX3CL1/fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium.

The olfactory epithelium (OE) is a site of massive adult neurogenesis where olfactory sensory neurons (OSNs) are continuously turned over. Tissue macrophages have been implicated in phagocytosis of degenerating cells but the molecular mechanisms that allow for their recruitment while maintaining a neurogenic microenvironment are poorly understood. This study reports that the neuroprotective chemokine CX3CL1 is expressed by OSNs and olfactory ensheathing cells. Monocyte-derived cells in the OE depend on CX3CL1-signalling for intraepithelial migration and apical dendrite expression. These observations are first to demonstrate phenotypic differences in appearance and distribution of monocyte-derived cells in nervous tissue due to CX3CR1 deficiency.

Case Study: Applying Rapid Flow Cytometry Analysis to CAPD Effluent.

Peritoneal dialysis (PD) peritonitis cases require rapid clinical interventions to ensure the best possible patient outcomes. Culture-dependent microbiology tools are slow and cannot provide clinicians with evidence to guide antimicrobial prescription practices in an appropriate time frame. Genotypic methods have met with limited success for analyzing continuous ambulatory PD effluent, with most centers still relying on culture-dependent microbiology. We present a case study in which we apply flow cytometry techniques to antibiotic-compromised effluent. We demonstrate, with supporting evidence, direct enumeration of bacterial and human immune cells, with results reported within 2 hours of receiving the clinical specimen.

Temporal flux in ß-lactam resistance among Klebsiella pneumoniae in Western Australia.

Our aim was to identify long-term ß-lactam resistance trends in local Klebsiella pneumoniae isolates, which are a common cause of sepsis in Western Australia. We studied three collections of K. pneumoniae isolates from Western Australia between 1977 and 2015 comprising contemporary blood culture (n = 98), multiresistant (n = 21) and historical (n = 50) isolates. Antimicrobial resistance was determined by Clinical and Laboratory Standards Institute agar dilution methods. PCR DNA sequencing identified ß-lactamase variants and porin mutations contributing to ß-lactam resistance. Isolates were genotyped by PFGE, multilocus sequence typing and a variable number tandem repeat method. From 1989 onwards, we detected the SHV-2a extended-spectrum ß-lactamase (ESBL) in ceftriaxone-resistant isolates, and in ceftazidime- and aztreonam-resistant isolates from 1993. Ceftriaxone, ceftazidime and aztreonam resistance persisted, with blaCTX-M types becoming the dominant ESBLs by 2010. CTX-M-15 was encountered in both multiresistant and blood culture isolates. Meropenem resistance was detected for the first time in 2011 in a locally isolated blaIMP-4-positive K. pneumoniae. We found sequence types ST23 and ST86 that occurred in multiple isolates from invasive infections. ST86 was the most common and maintained a high degree (90 %) of similarity by PFGE since 1977. Ceftazidime-resistant K. pneumoniae sequence types have caused invasive infections in Western Australia since 1993. Invasive isolates producing CTX-M-14 and CTX-M-15 appeared in Western Australia during the last decade, before the appearance of carbapenemases. The diversity of ß-lactam resistance and ß-lactamase resistance mechanisms in Western Australian K. pneumoniae has increased since ESBLs were first described locally.

Molecular mechanisms of ß-lactam resistance in carbapenemase-producing Klebsiella pneumoniae from Sri Lanka.

Carbapenemases are increasingly important antimicrobial resistance determinants. Little is known about the carbapenem resistance mechanisms in Sri Lanka. We examined 22 carbapenem-resistant Klebsiella pneumoniae from Sri Lanka to determine their ß-lactam resistance mechanisms. The predominant resistance mechanisms we detected in this study were OXA-181, NDM-1 carbapenemases and extended-spectrum ß-lactamase CTX-M-15. All isolates were then genotyped by pulsed-field gel electrophoresis, variable-number tandem repeat sequence analysis and multilocus sequence typing, and seven distinct genotypes were observed. Five OXA-181-positive Klebsiella pneumoniae isolates were genotypically related to an isolate of Indian origin. Multilocus sequence typing found that these related isolates belong to ST-14, which has been associated with dissemination of OXA-181 from the Indian subcontinent. Other genotypes we discovered were ST-147 and ST-340, also associated with intercontinental spread of carbapenemases of suspected subcontinental origin. The major porin genes ompK35 and ompK36 from these isolates had insertions, deletions and substitutions. Some of these were exclusive to strains within single pulsotypes. We detected one ompK36 variant, ins AA134-135GD, in six ST-14- and six ST-147, blaOXA-181-positive isolates. This porin mutation was an independent predictor of high-level meropenem resistance in our entire Sri Lankan isolate collection (P=0.0030). Analysis of the Sri Lankan ST-14 and ST-147 ins AA134-135GD-positive isolates found ST-14 was more resistant to meropenem than other isolates (mean MIC: 32±0 µg ml(-1) and 20±9.47 µg ml(-1), respectively, P=0.0277). The likely international transmission of these carbapenem resistance determinants highlights the need for regional collaboration and prospective surveillance of carbapenem-resistant Enterobacteriaceae.