Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.

Mitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves toward the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damaged mitochondria via its ubiquitin-binding domain. This myosin motor initiates the assembly of F-actin cages to encapsulate damaged mitochondria by forming a physical barrier that prevents refusion with neighboring populations. Loss of MYO6 results in an accumulation of mitophagosomes and an increase in mitochondrial mass. In addition, we observe downstream mitochondrial dysfunction manifesting as reduced respiratory capacity and decreased ability to rely on oxidative phosphorylation for energy production. Our work uncovers a crucial step in mitochondrial quality control: the formation of MYO6-dependent actin cages that ensure isolation of damaged mitochondria from the network

A Prospective Surveillance Study of Candidaemia : Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients

Funding This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. GR was also supported by a research fellowship grant from Gilead Sciences. The collection of the isolates was funded by a Gilead Fellowship to GR. Acknowledgments We are grateful to microbiology colleagues throughout Scotland for submitting isolates. Antimicrobial sensitivity testing was performed by the Mycology Reference Laboratory, Public Health England, Bristol.Peer reviewedPublisher PD

Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013

Acknowledgements This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. G. Ramage was also supported by a research fellowship grant from Gilead Sciences. We are grateful to microbiology colleagues throughout Scotland for submitting isolates.Peer reviewedPublisher PD

<i>Candida albicans</i> fungaemia following traumatic urethral catheterisation in a paraplegic patient with diabetes mellitus and candiduria treated by caspofungin

A 58-year-old paraplegic male, with long-term indwelling urethral catheter, developed catheter block. The catheter was changed, but blood-stained urine was drained intermittently. A long segment of the catheter was seen lying outside his penis, which indicated that the balloon of Foley catheter had been inflated in urethra. The misplaced catheter was removed and a new catheter was inserted correctly. Gentamicin 160 mg was given intravenously; meropenem 1 gram every eight hours was prescribed; antifungals were not given. Twenty hours later, this patient developed distension of abdomen, tachycardia, and hypotension; he was not arousable. Computed tomography of abdomen revealed inflamed uroepithelium of right renal pelvis and ureter, 4 mm lower ureteric calculus with gas in right ureter proximally, and vesical calculus containing gas in its matrix. Urine and blood culture yielded &lt;i&gt;Candida albicans&lt;/i&gt;. Identical sensitivity pattern of both isolates suggested that the source of the bloodstream infection was most likely urine. Both isolates formed consistently high levels of biofilm formation in vitro as assessed using a biofilm biomass stain, and high levels of resistance to voriconazole were observed. Both amphotericin B and caspofungin showed good activity against the biofilms. HbA1c was 111 mmol/mol. This patient was prescribed human soluble insulin and caspofungin 70 mg followed by 50 mg daily intravenously. He recovered fully from candidemia

Effects of cigarette advertising: reply to Boddewyn

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75370/1/j.1360-0443.1990.tb03535.x.pd

Puntaje de Tumbarello en la predicción de infección de vías urinarias por enterobaterias BLEE adquirida en la comunidad: estudio de prueba diagnóstica

Introducción: La infección urinaria adquirida por enterobacterias BLEE es un problema creciente, con prevalencia en nuestro país entre el 4 al 11%. Debido a la alta mortalidad asociada a las infecciones por estos gérmenes, al no escoger de forma adecuada el tratamiento empírico (11%), herramientas como el puntaje de Tumbarello deben ser correctamente evaluadas para definir su utilidad en la elección del tratamiento de estos pacientes. Objetivos: Determinar la prevalencia de infección urinaria por enterobacterias BLEE adquirida en la comunidad, y si el puntaje de Tumbarello es de utilidad para la predicción de la misma. Metodología: Se realizará un estudio de prueba diagnóstica en pacientes con infección urinaria adquirida en la comunidad, causada por enterobacterias, que cumplan criterios de inclusión y ninguno de exclusión, de las instituciones Hospital Universitario Clínica San Rafael y Clínica Fundadores. Resultados: La prevalencia de infección urinaria por enterobacterias BLEE fue del 28% (95% IC 0.18 – 0.35). La precisión del modelo de Tumbarello es del 99.98% (LR+ 15). Con un puntaje ≤ 3 el OR de cursar con infección urinaria por enterobacterias BLEE es 3.07 (95% IC 1.08 – 9.51), si el puntaje es ≥ 6 el OR es 2.03 (95% IC 0.75 – 5.41). Conclusión: La prevalencia por infección urinaria multirresistente es una condición de prevalencia creciente en nuestro medio. El puntaje de Tumbarello es una herramienta útil para descartar infecciones por estos gérmenes, no logrando determinar que sea de utilidad para la confirmación de las misas.Abstract. Introduction: Urinary tract infections caused by ESBL enterobacteriae are a growing problem, with prevalence in our country between 4 to 11%. Given the high mortality associated with this infection, if the empiric treatment is inadequate (11%), tolls like the Tumbarello score most be adequately evaluated to define its utility in the election of the treatment for those patients. Objectives: Define the prevalence of community acquired urinary tract infection caused by ESBL enterobacteriae, and if the Tumbarello score is useful in its prediction. Methodology: This is a diagnostic test trial, whit community acquired urinary tract infection patients, caused by enterobacteriae, which fulfill the inclusion criteria and none of exclusion, of the institution Hospital Universitario Clínica San Rafael and Clínica Fundadores. Results: The prevalence of ESBL enterobacteriae community tract infection was 28% (95% IC 0.18 – 0.35). The precision of the Tumbarello model in 99.98% (LR+ 15). With a score ≤ 3 the OR of having ESBL enterobacteriae community tract infection is 3.07 (95% IC 1.08 – 9.51), if the cutoff is ≥ 6 the OR is 2.03 (95% IC 0.75 – 5.41). Conclusion: The prevalence of multiresistant urinary tract infection are an increasing problem in our country. The Tumbarello score is an useful toll to dismiss infections caused by this bacteria, however it is no useful in the diagnosis of his type of infection.Otr

Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity

Background: Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.&lt;p&gt;&lt;/p&gt; Results: Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.&lt;p&gt;&lt;/p&gt; Conclusions: Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.&lt;p&gt;&lt;/p&gt

Carbapenem-Sparing Antibiotic Regimens for Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Intensive Care Unit

A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens were considered appropriate in 12% of episodes according to the Vitek 2 System and in 100% based on E-test

Outbreak of colistin-resistant, carbapenemase-producing klebsiella pneumoniae: Are we at the end of the road?

Carbapenem-resistant Klebsiella pneumoniae strains that produce K. pneumoniae carbapenemase (KPC) have spread globally in the last decade. Colistin is a key agent in treating infections caused by this pathogen. In this issue of the Journal of Clinical Microbiology, Giani et al. (T. Giani, F. Arena, G. Vaggelli, V. Conte, A Chiarell, L. H. De Angelis, R. Fornaini, M. Grazzini, F. Niccolini, P. Pecile, and G. M. Rossolini, J Clin Microbiol 53:3341–3344, 2015, http://dx.doi.org/10.1128/JCM.01017-15) describe a sustained outbreak of colistin-resistant KPC-producing K. pneumoniae