Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi.

Taurine is a fundamental mediator of homeostasis that exerts multiple roles to confer protection against oxidant stress. The development of hypertension, muscle/neuroassociated disorders, hepatic cirrhosis, cardiac dysfunction and ischemia/reperfusion are examples of some injuries that are linked with oxidative stress. The present review gives a comprehensive description of all the underlying mechanisms of taurine, with the aim to explain its anti-oxidant actions. Taurine is regarded as a cytoprotective molecule due to its ability to sustain normal electron transport chain, maintain glutathione stores, upregulate anti-oxidant responses, increase membrane stability, eliminate inflammation and prevent calcium accumulation. In parallel, the synergistic effect of taurine with other potential therapeutic modalities in multiple disorders are highlighted. Apart from the results derived from research findings, the current review bridges the gap between bench and bedside, providing mechanistic insights into the biological activity of taurine that supports its potential therapeutic efficacy in clinic. In the future, further clinical studies are required to support the ameliorative effect of taurine against oxidative stress. Contents1. Introduction 2. The role of taurine in homeostasis 3. The role of taurine against oxidative stress and its underlying molecular mechanisms 4. The beneficial effect of taurine against neuro-associated disorders 5. The anti-oxidant efficacy of taurine against cardiacassociated oxidative stress 6. The regulatory importance of taurine in ischemia and reperfusion 7. The anti-oxidant efficacy of taurine against muscle-associated disorders 8. The anti-oxidant efficacy of taurine against hepatic-associated stress 9. The anti-oxidant properties of taurine in various toxicmediated insults 10. Conclusions

| INTRODUC TI ONRhodotorula belongs to the phylum Basidiomycota and forms spherical-to-ellipsoidal budding yeast as well as rudimentary hyphae and small capsules. 1 It is widely distributed in the environment and is also found in the normal flora of the human gastrointestinal, respiratory and genital system as well as in the moist areas of the skin. 2 Even though it had been considered nonpathogenic, in the last decades there is growing evidence that it can be important human pathogen, especially in immunocompromised hosts, causing a variety of different infections, such as fungaemia, meningitis, peritoneal dialysis-associated peritonitis and keratitis. 3,4 The purpose of this study was to systemically review all published cases of Rhodotorula infections in the literature and describe the epidemiology, microbiology, treatment and outcomes of these infections in humans. SummaryBackground: Fungal infections by Rhodotorula species are increasingly reported in the literature and consist of bloodstream infections, especially in patients with central venous catheters (CVC), as well as central nervous system (CNS), ocular and other less frequent infections. Objectives: The aim of this systematic review was to record and evaluate all available evidence regarding infections by Rhodotorula species. Methods: Systematic review of PubMed (through 9 August 2017) for studies providing epidemiological, clinical, microbiological, as well as treatment data and outcomes of Rhodotorula species infections.Results: A total of 111 studies, containing data of 248 patients, were eventually included in the analysis. The most common Rhodotorula infections were those of bloodstream, CNS and ocular infections, as well as peritoneal dialysis-associated peritonitis.Epidemiology of each type of infection was different, with the bloodstream ones being more common in patients with malignancy and CVCs, while those of the CNS were more common in patients with AIDS. Mortality was variable being higher in CNS infections. Amphotericin B remains the most common agent used for treatment, irrespectively of the infection site. Conclusions: This systematic review thoroughly describes fungal infections byRhodotorula species and provides information on their epidemiology, clinical picture, microbiology, treatment and outcomes. K E Y W O R D S fungaemia, fungal infection, keratitis, meningitis, peritonitis, Rhodotorula | 91 IOANNOU et Al. with the following text-word: Rhodot*[tw]. Day of last search was 9 August 2017. | Study selectionStudies were included in analysis if they met the following criteria: (a) published in English; and (b) reporting data on patients' clinical characteristics, microbiology, treatment and outcomes. From the analysis were excluded studies with the following criteria: (a) secondary research papers (eg, reviews), editorials and papers not reporting results on primary research; (b) studies not in humans; (c) studies on colonisation but not infection by Rhodotorula; and (d) studies not in English. Two investigators (PI and RV) using Ab...

Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations (n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations.