Colicin-like bacteriocins as novel therapeutic agents for the treatment of chronic biofilm-mediated infection.

The emergence of pan-resistant strains of Gram-negative pathogens and the ability of many bacteria to form multidrug-resistant biofilms during chronic infection poses the grave threat of bacterial infections that are truly untreatable with our current armoury of antibiotics. Despite obvious clinical need, few new antibiotics have entered clinical practice in recent years. For 'difficult to treat' Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli, where the presence of outer membrane and multidrug-efflux pumps severely limit the effectiveness of whole classes of antibiotics, the need is particularly pressing. An alternative approach to antimicrobial treatment is to use the well-characterized species-specific colicin-like bacteriocins which are produced by a wide range of Gram-negative bacteria, including Pseudomonas aeruginosa and Escherichia coli. Our current work on colicin-like bacteriocins aims to determine whether these potent antimicrobial agents are effective at killing bacteria growing in the biofilm state and during infection.

Teacher and Student Views on the Feasibility of Peer to Peer Education as a Model to Educate 16-18 Year Olds on Prudent Antibiotic Use-A Qualitative Study.

Peer education (PE) has been used successfully to improve young peoples' health-related behaviour. This paper describes a qualitative evaluation of the feasibility of university healthcare students delivering PE, covering self-care and antibiotic use for infections, to biology students in three UK schools (16-18 years), who then educated their peers. Twenty peer educators (PEds) participated in focus groups and two teachers took part in interviews to discuss PE feasibility. Data were analysed inductively. All participants reported that teaching students about antibiotic resistance was important. PE was used by PEds to gain communication skills and experience for their CV. PEds confidence increased with practice and group delivery. Interactive activities and real-life illness scenarios facilitated enjoyment. Barriers to PE were competing school priorities, no antibiotic content in the non-biology curriculum, controlling disruptive behaviour, and evaluation consent and questionnaire completion. Participation increased PEds' awareness of appropriate antibiotic use. This qualitative study supports the feasibility of delivering PE in schools. Maximising interactive and illness scenario content, greater training and support for PEds, and inclusion of infection self-care and antibiotics in the national curriculum for all 16-18-year olds could help facilitate greater antibiotic education in schools. Simplifying consent and data collection procedures would facilitate future evaluations.

Peer-Education as a Tool to Educate on Antibiotics, Resistance and Use in 16-18-Year-Olds: A Feasibility Study.

Peer education (PE) interventions may help improve knowledge and appropriate use of antibiotics in young adults. In this feasibility study, health-care students were trained to educate 16-18 years old biology students, who then educated their non-biology peers, using e-Bug antibiotic lessons. Knowledge was assessed by questionnaires, and antibiotic use by questionnaire, SMS messaging and GP record searches. Five of 17 schools approached participated (3 PE and 2 control (usual lessons)). 59% (10/17) of university students and 28% (15/54) of biology students volunteered as peer-educators. PE was well-received; 30% (38/127) intervention students and 55% (66/120) control students completed all questionnaires. Antibiotic use from GP medical records (54/136, 40% of students' data available), student SMS (69/136, 51% replied) and questionnaire (109/136, 80% completed) data showed good agreement between GP and SMS (kappa = 0.72), but poor agreement between GP and questionnaires (kappa = 0.06). Median knowledge scores were higher post-intervention, with greater improvement for non-biology students. Delivering and evaluating e-Bug PE is feasible with supportive school staff. Single tiered PE by university students may be easier to regulate and manage due to time constraints on school students. SMS collection of antibiotic data is easier and has similar accuracy to GP data.

Current climate for digital game-based learning of science in further and higher education.

Digital game-based learning (DGBL) is being used increasingly as an alternative learning tool to teach science in further and higher education. A variety of digital game formats currently exist for science learning, alongside diverse methods for their implementation and evaluation. This paper aims to provide a broad summary of the field by discussing the current platforms for DGBL and examples of games played on them. These include gamified simulations and traditional digital games delivered through personal computer and online software; mobile games delivered through downloaded applications for devices such as tablets and mobile phones; and educational modifications of commercial games, known amongst gamers as 'mods'. To conclude the summary, the paper discusses the current challenges and barriers associated with DGBL in further and higher science education, and potential strategies researchers may consider to overcome them.

Activity of Species-specific Antibiotics Against Crohn's Disease-Associated Adherent-invasive Escherichia coli.

BACKGROUND: Crohn's disease (CD) is associated with bacterial dysbiosis that frequently includes colonization by adherent-invasive Escherichia coli (AIEC). AIEC are adept at forming biofilms and are able to invade host cells and stimulate the production of proinflammatory cytokines. The use of traditional antibiotics for the treatment of CD shows limited efficacy. In this study, we investigate the use of species-specific antibiotics termed colicins for treatment of CD-associated AIEC. METHODS: Colicin activity was tested against a range of AIEC isolates growing in the planktonic and biofilm mode of growth. Colicins were also tested against AIEC bacteria associated with T84 intestinal epithelial cells and surviving inside RAW264.7 macrophages using adhesion assays and gentamicin protection assay, respectively. Uptake of colicins into eukaryotic cells was visualized using confocal microscopy. The effect of colicin treatment on the production of proinflammatory cytokine tumor necrosis factor alpha by macrophages was assessed by an enzyme-linked immunosorbent assay. RESULTS: Colicins show potent activity against AIEC bacteria growing as biofilms when delivered either as a purified protein or through a colicin-producing bacterial strain. In addition, colicins E1 and E9 are able to kill cell-associated and intracellular AIEC, but do not show toxicity toward macrophage cells or stimulate the production of proinflammatory cytokines. Colicin killing of intracellular bacteria occurs after entry of colicin protein into AIEC-infected macrophage compartments by actin-mediated endocytosis. CONCLUSIONS: Our results demonstrate the potential of colicins as highly selective probiotic therapeutics for the eradication of E. coli from the gastrointestinal tract of patients with CD.