Deletion of the β-Acetoacetyl Synthase FabY in Pseudomonas aeruginosa Induces Hypoacylation of Lipopolysaccharide and Increases Antimicrobial Susceptibility

The β-acetoacetyl-acyl carrier protein synthase FabY is a key enzyme in the initiation of fatty acid biosynthesis in Pseudomonas aeruginosa. Deletion of fabY results in an increased susceptibility of P. aeruginosa in vitro to a number of antibiotics, including vancomycin and cephalosporins. Because antibiotic susceptibility can be influenced by changes in membrane lipid composition, we determined the total fatty acid profile of the ΔfabY mutant, which suggested alterations in the lipid A region of the lipopolysaccharide. The majority of lipid A species in the ΔfabY mutant lacked a single secondary lauroyl group, resulting in hypoacylated lipid A. Adding exogenous fatty acids to the growth media restored the wild-type antibiotic susceptibility profile and the wild-type lipid A fatty acid profile. We suggest that incorporation of hypoacylated lipid A species into the outer membrane contributes to the shift in the antibiotic susceptibility profile of the ΔfabY mutant.     

An exploration of nurse-physician perceptions of collaborative behaviour

Interprofessional collaboration is a key element in providing safe, holistic patient care in the acute care setting. Trended data at a community hospital indicated opportunities for improvement in collaboration on micro, meso, and macro levels. The aim of this survey study was to assess the current state of collaboration between frontline nurses and physicians at a non-academic acute care hospital. A convenience sample of participants was recruited with a final respondent sample of 355 nurses and 82 physicians. The results indicated that physicians generally perceived greater collaboration than nurses. Physician ratings did not vary by primary practice area, whereas nurse ratings varied by clinical practice area. Nurse ratings were the lowest in the operating room and the highest in the emergency department. Text-based responses to an open-ended question were analysed by role and coded by two independent research teams. Emergent themes emphasised the importance of rounding, roles, respect, and communication. Despite recognition of the need for improved collaboration and relational behaviours, strategies to improve collaborative practice must be fostered at the meso level by organisational leaders and customised to address micro-level values. At the study site, findings have been used to address and improve collaboration towards the goal of becoming a high reliability organisation.     

γH2AX as a novel endpoint to detect DNA damage: Applications for the assessment of the in vitro genotoxicity of cigarette smoke

Histone H2AX is rapidly phosphorylated to become γH2AX after exposure to DNA-damaging agents that cause double-strand DNA breaks (DSBs). γH2AX can be detected and quantified by numerous methods, giving a direct correlation with the number of DSBs. This relationship has made γH2AX an increasingly utilised endpoint in multiple scientific fields since its discovery in 1998. Applications include its use in pre-clinical drug assessment, as a biomarker of DNA damage and in in vitro mechanistic studies.Here, we review current in vitro regulatory and non-regulatory genotoxicity assays proposing the γH2AX assay as a potential complement to the current test battery.Additionally, we evaluate the use of the γH2AX assay to measure DSBs in vitro in tobacco product testing.