Antimicrobial resistance (AMR) has been declared one of the top 10 global public health challenges of our age by the World Health Organization, and the World Bank describes AMR as a crisis affecting the finance, health, and agriculture sectors and a major threat to the attainment of Sustainable Development Goals. But what is AMR? It is a phenotype that evolves in microbes exposed to antimicrobial molecules and causes dangerous infections. This suggests that scientists and healthcare workers should be on the frontline in the search for sustainable solutions to AMR.
View Article and Find Full Text PDFis consistently ranked among the most problematic multidrug-resistant bacterial pathogens in healthcare systems. Developing novel treatments requires a better understanding of its interaction with the host environment. Although bacteria can synthesize fatty acids, emerging findings suggest a potential preference for their acquisition from the host.
View Article and Find Full Text PDFDPANN is a widespread and diverse group of archaea characterized by their small size, reduced genome, limited metabolic pathways, and symbiotic existence. Known DPANN species are predominantly obligate ectosymbionts that depend on their host for proliferation. The structural and molecular details of host recognition, host-DPANN intercellular communication, and host adaptation in response to DPANN attachment remain unknown.
View Article and Find Full Text PDFIn supermarkets and chemists worldwide, consumers are faced with an array of antimicrobial domestic cleaning and personal hygiene products purporting to kill germs and keep people safe. Many of these proven active ingredients (biocides) encourage the development of antimicrobial resistance (AMR) in microbes and microbial populations, in turn increasing the likelihood of AMR infections. In order to understand and address the selective pressure towards AMR posed by the unrestricted use of biocides, it is necessary to understand which biocides are most frequently found in consumer products and the current regulatory framework that governs their use.
View Article and Find Full Text PDFConcerns exist that widespread use of antiseptic or disinfectant biocides could contribute to the emergence and spread of multidrug-resistant bacteria. To investigate this, we performed transposon-directed insertion-site sequencing (TraDIS) on the multidrug-resistant pathogen, Acinetobacter baumannii, exposed to a panel of ten structurally diverse and clinically relevant biocides. Multiple gene targets encoding cell envelope or cytoplasmic proteins involved in processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, were identified to have effects on bacterial fitness upon biocide exposure, suggesting that these compounds may have intracellular targets in addition to their known effects on the cell envelope.
View Article and Find Full Text PDFThe rapid increase and spread of Gram-negative bacteria resistant to many or all existing treatments threaten a return to the preantibiotic era. The presence of bacterial polysaccharides that impede the penetration of many antimicrobials and protect them from the innate immune system contributes to resistance and pathogenicity. No currently approved antibiotics target the polysaccharide regions of microbes.
View Article and Find Full Text PDFTo kill bacteria, bacteriophages (phages) must first bind to a receptor, triggering the release of the phage DNA into the bacterial cell. Many bacteria secrete polysaccharides that had been thought to shield bacterial cells from phage attack. We use a comprehensive genetic screen to distinguish that the capsule is not a shield but is instead a primary receptor enabling phage predation.
View Article and Find Full Text PDFCoordination of bacterial stress response mechanisms is critical for long-term survival in harsh environments for successful host infection. The general and specific stress responses of well-studied Gram-negative pathogens like Escherichia coli are controlled by alternative sigma factors, archetypically RpoS. The deadly hospital pathogen Acinetobacter baumannii is notoriously resistant to environmental stresses, yet it lacks RpoS, and the molecular mechanisms driving this incredible stress tolerance remain poorly defined.
View Article and Find Full Text PDFAcinetobacter baumannii and Klebsiella pneumoniae are opportunistic pathogens frequently co-isolated from polymicrobial infections. The infections where these pathogens co-exist can be more severe and recalcitrant to therapy than infections caused by either species alone, however there is a lack of knowledge on their potential synergistic interactions. In this study we characterise the genomes of A.
View Article and Find Full Text PDFBiofilm formation and capsule production are known microbial strategies used by bacterial pathogens to survive adverse conditions in the hospital environment. The relative importance of these strategies individually is unexplored. This project aims to compare the contributory roles of biofilm formation and capsule production in bacterial survival on hospital surfaces.
View Article and Find Full Text PDFNaturally competent bacteria encode sophisticated protein machinery for the uptake and translocation of exogenous DNA into the cell. If this DNA is integrated into the bacterial genome, the bacterium is said to be naturally transformed. Most competent bacterial species utilise type IV pili for the initial DNA uptake step.
View Article and Find Full Text PDFis a critically important pathogen known for its widespread antibiotic resistance and ability to persist in hospital-associated environments. Whilst the majority of infections are hospital-acquired, infections from outside the hospital have been reported with high mortality. Despite this, little is known about the natural environmental reservoir(s) of and the virulence potential underlying non-clinical strains.
View Article and Find Full Text PDFBackground: Biocide disinfectants are essential tools in infection control, but their use can inadvertently contribute to emergence of antibiotic-resistant bacteria. In this study we systematically examine the effect of the biocide benzalkonium chloride, which is primarily used for surface disinfection but is also present as a preservative in many consumer products, on the activity of aminoglycoside antibiotics in Acinetobacter baumannii.
Methods: The effect of subinhibitory BAC on aminoglycoside treatment of A.
Antimicrobial resistance genes, including multidrug efflux pumps, evolved long before the ubiquitous use of antimicrobials in medicine and infection control. Multidrug efflux pumps often transport metabolites, signals and host-derived molecules in addition to antibiotics or biocides. Understanding their ancestral physiological roles could inform the development of strategies to subvert their activity.
View Article and Find Full Text PDFThe production of capsular polysaccharides by Klebsiella pneumoniae protects the bacterial cell from harmful environmental factors such as antimicrobial compounds and infection by bacteriophages (phages). To bypass this protective barrier, some phages encode polysaccharide-degrading enzymes referred to as depolymerases to provide access to cell surface receptors. Here, we characterized the phage RAD2, which infects K.
View Article and Find Full Text PDFInfections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K.
View Article and Find Full Text PDFGalleria mellonella has risen to fame as an invertebrate model organism given its ethical advantages, low maintenance costs, rapid reproduction time, short life cycle, high number of progeny, tolerance for human body temperatures, innate immune system and similarities to mammalian host models. It is increasingly being utilised to evaluate in vivo toxicity and efficacy of chemical compounds and antimicrobials, modelling microbial (bacterial, fungal and viral) pathogenicity and assessing host-pathogen interaction during infection. During this molecular age of genomic, transcriptomic, proteomic and genetic manipulation approaches, our understanding of microbial pathogenicity and host-pathogen interactions has deepened from high-throughput molecular studies performed in G.
View Article and Find Full Text PDFResistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug-resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it is reasonable to explore their possible utility in treating fungal infections.
View Article and Find Full Text PDFThe serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of to cause infection, but it is an incompletely understood virulence trait. Identifying and characterizing the factors responsible for preventing activation of, and killing by, serum complement could inform new approaches to treatment of infections.
View Article and Find Full Text PDFCapsule is a key virulence factor in many bacterial species, mediating immune evasion and resistance to various physical stresses. While many methods are available to quantify and compare capsule production between different strains or mutants, there is no widely used method for sorting bacteria based on how much capsule they produce. We have developed a method to separate bacteria by capsule amount, using a discontinuous density gradient.
View Article and Find Full Text PDFinfections affect infants and the immunocompromised, and the recent emergence of hypervirulent and multidrug-resistant lineages is a critical health care concern. Hypervirulence in is mediated by several factors, including the overproduction of extracellular capsule. However, the full details of how capsule biosynthesis is achieved or regulated are not known.
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