1,721,012 research outputs found
UsingGalleria mellonellato study pathogen dissemination and anti-infective surface coatings
No full textHospital associated infections and localised hospital outbreaks are a major challenge for infection control teams (ICTs) in hospitals around the world. Advances in artificial intelligence and infection modelling have enabled ICT teams to better predict and trace infection spread. However, it is notoriously difficult to replicate bacterial dissemination or validate prediction models in a laboratory setting due to a lack of effective in vivo models. In this work, we sought to develop Galleria mellonella as a model organism to replicate the dissemination of pathogens in a hospital intensive care unit (ICU). By combining this model organism with 3D printed models of a real hospital ICU, we are able to demonstrate that larvae do disseminate the multidrug resistant pathogen Acinetobacter baumannii within this ICU model and that it is possible to use this model to identify infection hotspots. Importantly, this model can also be used for intervention strategy testing as we also show that bacterial dissemination can be significantly mitigated by the introduction of antimicrobial wall surface coatings. This model provides a robust platform for the testing of antimicrobial surface coatings as well as the study of genetic determinants with a role in pathogen dissemination
Burns and Biofilms: Priority pathogens and in vivo models
Get PDFCopyright © 2021 The Author(s). Burn wounds can create significant damage to human skin, compromising one of the key barriers to infection. The leading cause of death among burn wound patients is infection. Even in the patients that survive, infections can be notoriously difficult to treat and can cause lasting damage, with delayed healing and prolonged hospital stays. Biofilm formation in the burn wound site is a major contributing factor to the failure of burn treatment regimens and mortality as a result of burn wound infection. Bacteria forming a biofilm or a bacterial community encased in a polysaccharide matrix are more resistant to disinfection, the rigors of the host immune system, and critically, more tolerant to antibiotics. Burn wound-associated biofilms are also thought to act as a launchpad for bacteria to establish deeper, systemic infection and ultimately bacteremia and sepsis. In this review, we discuss some of the leading burn wound pathogens and outline how they regulate biofilm formation in the burn wound microenvironment. We also discuss the new and emerging models that are available to study burn wound biofilm formation in vivo.British Society for Antimicrobial Chemotherapy BSAC-2018-0095; Innovate UK Smart Grant 37800, FRAME, Young European Research University Network Mobility Award, NC3Rs PhD Studentship NC/V001582/1; BBSRC New Investigator Award BB/V007823/1; Academy of Medical Sciences; Wellcome Trust; UK Government Department of Business, Energy and Industrial Strategy; British Heart Foundation/Diabetes UK Springboard Award [SBF006\1040]
Understanding the Consumption of Antimicrobial Resistance–Related Content on Social Media: Twitter Analysis
Get PDFBackground: Antimicrobial resistance (AMR) is one of the most pressing concerns in our society. Today, social media can function as an important channel to disseminate information about AMR. The way in which this information is engaged with depends on a number of factors, including the target audience and the content of the social media post.
Objective: The aim of this study is to better understand how AMR-related content is consumed on the social media platform Twitter and to understand some of the drivers of engagement. This is essential to designing effective public health strategies, raising awareness about antimicrobial stewardship, and enabling academics to effectively promote their research on social media.
Methods: We took advantage of unrestricted access to the metrics associated with the Twitter bot @AntibioticResis, which has over 13,900 followers. This bot posts the latest AMR research in the format of a title and a URL link to the PubMed page for an article. The tweets do not contain other attributes such as author, affiliation, or journal. Therefore, engagement with the tweets is only affected by the words used in the titles. Using negative binomial regression models, we measured the impact of pathogen names in paper titles, academic attention inferred from publication counts, and general attention estimated from Twitter on URL clicks to AMR research papers.
Results: Followers of @AntibioticResis consisted primarily of health care professionals and academic researchers whose interests comprised mainly AMR, infectious diseases, microbiology, and public health. Three World Health Organization (WHO) critical priority pathogens—Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae—were positively associated with URL clicks. Papers with shorter titles tended to have more engagements. We also described some key linguistic characteristics that should be considered when a researcher is trying to maximize engagement with their publication.
Conclusions: Our finding suggests that specific pathogens gain more attention on Twitter than others and that the levels of attention do not necessarily correspond to their status on the WHO priority pathogen list. This suggests that more targeted public health strategies may be needed to raise awareness about AMR among specific pathogens. Analysis of follower data suggests that in the busy schedules of health care professionals, social media offers a fast and accessible gateway to staying abreast of the latest developments in this field
Using next generation antimicrobials to target the mechanisms of infection
No full textThe remarkable impact of antibiotics on human health is being eroded at an alarming rate by the emergence of multidrug resistant pathogens. There is a recognised consensus that new strategies to tackle infection are urgently needed to limit the devasting impact of antibiotic resistance on our global healthcare infrastructure. Next generation antimicrobials (NGAs) are compounds that target bacterial virulence factors to disrupt pathogenic potential without impacting bacterial viability. By disabling the key virulence factors required to establish and maintain infection, NGAs make pathogens more vulnerable to clearance by the immune system and can potentially render them more susceptible to traditional antibiotics. In this review, we discuss the developing field of NGAs and how advancements in this area could offer a viable standalone alternative to traditional antibiotics or an effective means to prolong antibiotic efficacy when used in combination.</p
Antimicrobial inks: the anti-infective applications of bioprinted bacterial polysaccharides
No full textBioprinting is a rapidly emerging technology with the potential to transform the biomedical sector. Here, we discuss how a range of bacterial polysaccharides with antibiofilm and antibacterial activity could be used to augment current bioink formulations to improve their biocompatibility and tackle the spread of antibiotic-resistant infections.</p
Engineering biology approaches to modulate bacterial biofilms
No full textBuilding on a productive two decades of advancements in synthetic biology, engineering biology now promises to enable the implementation and scale-up of novel biological systems tailored to tackle urgent global challenges. Here we explore the latest engineering biology approaches for the control and modification of bacterial biofilms with exciting new functionalities.<br/
A high-efficiency scar-free genome editing toolkit for Acinetobacter baumannii
No full textBackgroundThe current mutagenesis tools for Acinetobacter baumannii
leave selection markers or residual sequences behind, or involve
tedious counterselection and screening steps. Furthermore, they are
usually adapted for model strains, rather than for MDR clinical
isolates.ObjectivesTo develop a scar-free genome-editing tool suitable for chromosomal and plasmid modifications in MDR A. baumannii AB5075.MethodsWe prove the efficiency of our adapted genome-editing system by deleting the multidrug efflux pumps craA, cmlA5
and resistance island 2 (RI2), as well as curing plasmid p1AB5075, and
combining these mutations. We then characterized the susceptibility of
the mutants compared with the WT to different antibiotics (i.e.
chloramphenicol, amikacin and tobramycin) by disc diffusion assays and
determined the MIC for each strain.ResultsWe successfully adapted the genome-editing protocol to A. baumannii
AB5075, achieving a double recombination frequency close to 100% and
routinely securing the construction of a mutant within 10 working days.
Furthermore, we show that both CraA and p1AB5075 are involved in
chloramphenicol resistance, and that RI2 and p1AB5075 play a role in
resistance to amikacin and tobramycin.ConclusionsWe have developed a versatile and highly efficient genome-editing tool for A. baumannii.
We have demonstrated it can be used to modify both the chromosome and
native plasmids. By challenging the method, we show the role of CraA and
p1AB5075 in antibiotic resistance.</div
Modulating biofilm can potentiate activity of novel plastic-degrading enzymes
No full textPlastic pollution is an increasing global issue desperately requiring a solution. Only 9% of all plastic waste has been recycled, and whilst recycling gives a second life to plastic, it is costly and there are limited downstream uses of recycled plastic, therefore an alternative is urgently needed. Biodegradation of plastic by microorganisms is a developing field of interest with the potential for bioreactors to be used alongside recycling to degrade plastic that may otherwise be sent to landfill. Here, we have identified two novel polyethylene terephthalate (PET) degrading enzymes through genomic mining and characterised their activity, including their ability to degrade PET. One of the main roadblocks facing the development of microbial enzymes as a plastic biodegradation solution, is that their efficiency is too low to facilitate development as bioremediation tools. In an innovative approach to tackle this roadblock, we hypothesised that enhancing a bacteria’s ability to attach to and form a biofilm on plastic could maximise the local concentration of the enzyme around the target substrate, therefore increasing the overall rate of plastic degradation. We found that increasing biofilm levels, by manipulating the levels of the second messenger, Cyclic-di-GMP, led to increased levels of polyester degradation in cells expressing novel and well characterised polyester-degrading enzymes. This indicates that modulating biofilm formation is a viable mechanism to fast track the development of bacterial plastic bioremediation solutions
Contribution of Cyclic di-GMP in the Control of Type III and Type VI Secretion in Pseudomonas aeruginosa
No full textBacteria produce toxins to enhance their competitiveness in the colonization of an environment as well as during an infection. The delivery of toxins into target cells is mediated by several types of secretion systems, among them our focus is Type III and Type VI Secretion Systems (T3SS and T6SS, respectively). A thorough methodology is provided detailing how to identify if cyclic di-GMP signaling plays a role in the P. aeruginosa toxin delivery mediated by T3SS or T6SS. This includes in vitro preparation of the samples for Western blot analysis aiming at detecting possible c-di-GMP-dependent T3SS/T6SS switch, as well as in vivo analysis using the model organism Galleria mellonella to demonstrate the ecological and pathogenic consequence of the switch between these two secretion systems
Using the Galleria mellonella burn wound and infection model to identify and characterize potential wound probiotics
No full textBurn wound infection is the leading cause of mortality among burn wound patients. One of the most commonly isolated bacterial burn wound pathogens is Pseudomonas aeruginosa, a notorious nosocomial multidrug-resistant pathogen. As a consequence of its recalcitrance to frontline antibiotic therapy, there is an urgent need to develop alternative treatment avenues to tackle this pathogen. One potential alternative infection prevention measure is to seed the wound bed with probiotic bacteria. Several species of Lactobacillus, a common commensal bacterium, have been previously reported to display growth inhibition activity against wound pathogens. Various species of this genus have also been shown to augment the wound healing process, which makes it a promising potential therapeutic agent. Due to the complexity of the burn wound trauma and burn wound infection, an in vivo model is required for the development of novel therapeutics. There are multiple in vivo models that are currently available, the most common among them being the murine model. However, mammalian burn wound infection models are logistically challenging, do not lend themselves to screening approaches and come with significant concerns around ethics and animal welfare. Recently, an invertebrate burn wound and infection model using G. mellonella has been established. This model addresses several of the challenges of more advanced animal models, such as affordability, maintenance and reduced ethical concerns. This study validates the capacity of this model to screen for potential wound probiotics by demonstrating that a variety of Lactobacillus spp. can limit P. aeruginosa burn wound infection and improve survival
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