Biguanide iridium(III) complexes with potent antimicrobial activity

We have synthesized novel organoiridium(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus (MRSA)) and high antifungal potency toward C. albicans and C. neoformans, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant Enterococci (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone

Lead, cadmium, zinc and copper in organisms of Lake Macquarie

Research Doctorate - Bachelor of Science (Honours)Lake Macquarie, the largest of many similarly-formed estuarine lakes on the NSW coast, was created by the inundation of a series of confluent river valleys due to a relative rise in sea level during the post-glacial transgression. The potential for effulent-induced pollution of the lake basin is partly governed by several physiographic and hydrologic features of Lake Macquarie. Tidal action is effectively damped by the restriction of flow caused by Swansea Channel. A number of small ephemeral or intermittent streams drain into Lake Macquarie from a catchment of 74,000 ha but most freshwater input comes via Cockle Creek at the northern end and Dora Creek on the south-western shore. Winds prevail from the south-east quarter in summer and from the north-west in winter with periods of transition between the major seasons. Sedimentation of the original valley system has created a rather flat-floored, shallow basin. Lake Macquarie's constricted and elevated entrance channel, small freshwater input, restricted wave and current action and the general basin morphology all result in a markedly depositional environment

Multiple Antibiotic Resistance in Arabidopsis Is Conferred by Mutations in a Chloroplast-Localized Transport Protein[C][W][OA]

Widespread antibiotic resistance is a major public health concern, and plants represent an emerging antibiotic exposure route. Recent studies indicate that crop plants fertilized with antibiotic-laden animal manure accumulate antibiotics; however, the molecular mechanisms of antibiotic entry and subcellular partitioning within plant cells remain unknown. Here, we report that mutations in the Arabidopsis (Arabidopsis thaliana) locus Multiple Antibiotic Resistance1 (MAR1) confer resistance, while MAR1 overexpression causes hypersensitivity to multiple aminoglycoside antibiotics. Additionally, yeast expressing MAR1 are hypersensitive to the aminoglycoside G418. MAR1 encodes a protein with 11 putative transmembrane domains with low similarity to ferroportin1 from Danio rerio. A MAR1:yellow fluorescent protein fusion localizes to the chloroplast, and chloroplasts from plants overexpressing MAR1 accumulate more of the aminoglycoside gentamicin, while mar1-1 mutant chloroplasts accumulate less than the wild type. MAR1 overexpression lines are slightly chlorotic, and chlorosis is rescued by exogenous iron. MAR1 expression is also down-regulated by low iron. These data suggest that MAR1 is a plastid transporter that is likely to be involved in cellular iron homeostasis and allows opportunistic entry of multiple antibiotics into the chloroplast

Trends in practice: attitudes and challenges in the diagnosis, treatment and management of HIV infection in Australia

As life expectancy for people living with human immunodeficiency virus (HIV) (PLWHIV) increases, management models for HIV infection are changing. To understand approaches to practice within this shifting climate and across different medical settings, in 2017 we conducted a baseline survey among the main medical practitioner groups responsible for HIV-infection care in Australia: hospital-based physicians (HBP), sexual health physicians (SHP) and 'accredited general practitioners' (referred to in 2017 study as 's100 GPs'), who are GPs authorised to prescribe HIV therapies after completing accredited national training. The follow-up survey presented here explores any changes in approaches, attitudes and challenges associated with HIV-infection management among the same practitioner groups: 17 HBP, 15 SHP and 69 accredited GP (referred to throughout as GP; includes those with sexual health diploma). Analysis of survey results showed practices remained largely similar between surveys, with a few notable exceptions. Greater consistency in attitudes, knowledge and approaches was observed between the practitioner specialty groups, with only small differences between modes of practice. A trend towards earlier initiation of HIV treatment was also identified, with a higher proportion of practitioners than baseline reporting they were comfortable beginning therapy on the day of HIV diagnosis. The impact of the introduction of two-drug therapy in Australia was also explored. Although the majority of survey respondents (and SHP in particular) expressed greater preference for three-drug compared with two-drug regimens, interest in two-drug regimens appears to be growing and may influence future prescribing practices. Addressing mental health issues for PLWHIV was again highlighted as a major priority, with practitioners overwhelmingly reporting mental health management as among their most difficult clinical challenges. Reduction in stigma/discrimination and better access to substance dependency programmes were also identified as unmet needs for this patient cohort. Consistent with our baseline survey, it appears targeted interventions and supports appropriate to this population are still required to improve overall wellbeing for PLWHIV