Distribution of the four type VI secretion systems in Pseudomonas aeruginosa and classification of their core and accessory effectors.

Bacterial type VI secretion systems (T6SSs) are puncturing molecular machines that transport effector proteins to kill microbes, manipulate eukaryotic cells, or facilitate nutrient uptake. How and why T6SS machines and effectors differ within a species is not fully understood. Here, we applied molecular population genetics to the T6SSs in a global population of the opportunistic pathogen Pseudomonas aeruginosa.

Cpx-signalling in modulates Lipid-A remodelling and resistance to last-resort antimicrobials.

Antibiotic resistance is a global healthcare crisis. Bacteria are highly adaptable and can rapidly acquire mechanisms of resistance towards conventional antibiotics. The permeability barrier conferred by the Gram-negative bacteria cell envelope constitutes a first line of defence against the action of antibiotics.

Combined functional genomic and metabolomic approaches identify new genes required for growth in human urine by multidrug-resistant ST131.

Unlabelled: Urinary tract infections (UTIs) are one of the most common bacterial infections in humans, with ~400 million cases across the globe each year. Uropathogenic (UPEC) is the major cause of UTI and increasingly associated with antibiotic resistance. This scenario has been worsened by the emergence and spread of pandemic UPEC sequence type 131 (ST131), a multidrug-resistant clone associated with extraordinarily high rates of infection.

Killing in the name of: T6SS structure and effector diversity.

The life of bacteria is challenging, to endure bacteria employ a range of mechanisms to optimize their environment, including deploying the type VI secretion system (T6SS). Acting as a bacterial crossbow, this system delivers effectors responsible for subverting host cells, killing competitors and facilitating general secretion to access common goods. Due to its importance, this lethal machine has been evolutionarily maintained, disseminated and specialized to fulfil these vital functions.

Diversity and prevalence of type VI secretion system effectors in clinical isolates.

is an opportunistic pathogen and a major driver of morbidity and mortality in people with Cystic Fibrosis (CF). The Type VI secretion system (T6SS) is a molecular nanomachine that translocates effectors across the bacterial membrane into target cells or the extracellular environment enabling intermicrobial interaction. encodes three T6SS clusters, the H1-, H2- and H3-T6SS, and numerous orphan islands.

Overcoming adversity: Building a remote interdisciplinary neurorehabilitation service during the COVID-19 pandemic.

Background: The COVID-19 pandemic necessitated rapid change in neurorehabilitation delivery at the Defence Medical Rehabilitation Centre (DMRC), with a reduction in inpatient capacity.

Aims And Method: An interdisciplinary remote working group developed a novel neurorehabilitation telerehabilitation (TR) model. The plan, do, study, act (PDSA) model was used to develop and monitor activity in the changing pandemic context and to identify clinical outputs, key themes and learning points.

Antimicrobial Weapons of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a robust and versatile organism capable of surviving and prospering in a diverse array of environments and is an opportunistic pathogen of humans. One reason for the success of this pathogen is the large arsenal of antimicrobial weapons that it possesses. Here we focus our attention on these antimicrobial weapons and how they give P.

Structure of ATP synthase from ESKAPE pathogen .

The global spread of multidrug-resistant infections urgently calls for the identification of novel drug targets. We solved the electron cryo-microscopy structure of the FF-adenosine 5'-triphosphate (ATP) synthase from in three distinct conformational states. The nucleotide-converting F subcomplex reveals a specific self-inhibition mechanism, which supports a unidirectional ratchet mechanism to avoid wasteful ATP consumption.

Differential Afa/Dr Fimbriae Expression in the Multidrug-Resistant Escherichia coli ST131 Clone.

Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains.

RpoN/Sfa2-dependent activation of the Pseudomonas aeruginosa H2-T6SS and its cognate arsenal of antibacterial toxins.

Pseudomonas aeruginosa uses three type six secretion systems (H1-, H2- and H3-T6SS) to manipulate its environment, subvert host cells and for microbial competition. These T6SS machines are loaded with a variety of effectors/toxins, many being associated with a specific VgrG. How P.

Review of neurological rehabilitation for Multiple Sclerosis in the British Military.

Multiple sclerosis (MS) is a progressive neurological disorder, classically presenting in working age adults, including those in the Armed Forces. The Defence Medical Rehabilitation Centre (DMRC) Stanford Hall offers vocationally focused neurorehabilitation services for service personnel (SP) with MS, with the goal to minimise disability, maximise independence and remain able to work.This paper has two aims.

Dissemination of Evidence-Based School Asthma Management Programs: Piloting Asthma 411 in an Urban Texas School District.

Background: The dissemination and implementation (D&I) of evidence-based initiative (EBIs) is critical to improved public health. The Asthma 411 EBI was piloted in Texas from 2013 to 2015. The pilot's evaluation assessed its effectiveness and identified approaches to support D&I of school-health EBIs.

Causalities of war: The connection between type VI secretion system and microbiota.

Microbiota niches have space and/or nutrient restrictions, which has led to the coevolution of cooperation, specialisation, and competition within the population. Different animal and environmental niches contain defined resident microbiota that tend to be stable over time and offer protection against undesired intruders. Yet fluxes can occur, which alter the composition of a bacterial population.

Using machine learning to examine the relationship between asthma and absenteeism.

In this study, we found that machine learning was able to effectively estimate student learning outcomes geo-spatially across all the campuses in a large, urban, independent school district. The machine learning showed that key factors in estimating the student learning outcomes included the number of days students were absent from school. In turn, one of the most important factors in estimating the number of days a student was absent was whether or not the student had asthma.

The T6SS-VgrG1b spike is topped by a PAAR protein eliciting DNA damage to bacterial competitors.

The type VI secretion system (T6SS) is a supramolecular complex involved in the delivery of potent toxins during bacterial competition. possesses three T6SS gene clusters and several and gene islands, the latter encoding the spike at the T6SS tip. The cluster encompasses seven genes whose organization and sequences are highly conserved in genomes, except for two genes that we called and We show that Tse7 is a Tox-GHH2 domain nuclease which is distinct from other T6SS nucleases identified thus far.

Probing the internal micromechanical properties of biofilms by Brillouin imaging.

Biofilms are organised aggregates of bacteria that adhere to each other or surfaces. The matrix of extracellular polymeric substances that holds the cells together provides the mechanical stability of the biofilm. In this study, we have applied Brillouin microscopy, a technique that is capable of measuring mechanical properties of specimens on a micrometre scale based on the shift in frequency of light incident upon a sample due to thermal fluctuations, to investigate the micromechanical properties of an active, live biofilm.

Visualizing Antimicrobials in Bacterial Biofilms: Three-Dimensional Biochemical Imaging Using TOF-SIMS.

Bacterial biofilms are groups of bacteria that exist within a self-produced extracellular matrix, adhering to each other and usually to a surface. They grow on medical equipment and inserts such as catheters and are responsible for many persistent infections throughout the body, as they can have high resistance to many antimicrobials. is an opportunistic pathogen that can cause both acute and chronic infections and is used as a model for research into biofilms.

RsmA and AmrZ orchestrate the assembly of all three type VI secretion systems in .

The type VI secretion system (T6SS) is a weapon of bacterial warfare and host cell subversion. The Gram-negative pathogen has three T6SSs involved in colonization, competition, and full virulence. H1-T6SS is a molecular gun firing seven toxins, Tse1-Tse7, challenging survival of other bacteria and helping to prevail in specific niches.

The Pseudomonas putida T6SS is a plant warden against phytopathogens.

Bacterial type VI secretion systems (T6SSs) are molecular weapons designed to deliver toxic effectors into prey cells. These nanomachines have an important role in inter-bacterial competition and provide advantages to T6SS active strains in polymicrobial environments. Here we analyze the genome of the biocontrol agent Pseudomonas putida KT2440 and identify three T6SS gene clusters (K1-, K2- and K3-T6SS).

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells.

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine.

The Intimin-Like Protein FdeC Is Regulated by H-NS and Temperature in Enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) is a Shiga-toxigenic pathogen capable of inducing severe forms of enteritis (e.g., hemorrhagic colitis) and extraintestinal sequelae (e.

The VgrG proteins are "à la carte" delivery systems for bacterial type VI effectors.

The bacterial type VI secretion system (T6SS) is a supra-molecular complex akin to bacteriophage tails, with VgrG proteins acting as a puncturing device. The Pseudomonas aeruginosa H1-T6SS has been extensively characterized. It is involved in bacterial killing and in the delivery of three toxins, Tse1-3.

F9 fimbriae of uropathogenic Escherichia coli are expressed at low temperature and recognise Galβ1-3GlcNAc-containing glycans.

Uropathogenic Escherichia coli (UPEC) is the leading causative agent of urinary tract infections (UTI) in the developed world. Among the major virulence factors of UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC strains typically possess a range of adhesins, with type 1 fimbriae and P fimbriae of the chaperone-usher class the best characterised.