Unlabelled: Zinc (Zn) is an essential cofactor for numerous bacterial proteins and altering Zn availability is an important component of host innate immunity. During infection, adaptation to both Zn deprivation and excess is critical for pathogenic bacteria development. To understand the adaptive responses to Zn availability of , a pathogen causing invasive infections of neonates, global transcriptional profiling was conducted.
View Article and Find Full Text PDFis a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated oxidative stresses. Here, we show that , a gene previously linked to iron import, is essential for manganese recruitment the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein.
View Article and Find Full Text PDFMetal ions are required by all organisms for the chemical processes that support life. However, in excess they can also exert toxicity within biological systems. During infection, bacterial pathogens such as Streptococcus pneumoniae are exposed to host-imposed metal intoxication, where the toxic properties of metals, such as copper, are exploited to aid in microbial clearance.
View Article and Find Full Text PDFAcquisition of the trace-element molybdenum the high-affinity ATP-binding cassette permease ModABC is essential for respiration in anaerobic and microaerophilic environments. This study determined the X-ray crystal structures of the molybdenum-recruiting solute-binding protein ModA from PAO1 in the metal-free state and bound to the group 6 metal oxyanions molybdate, tungstate, and chromate. PAO1 ModA has a non-contiguous dual-hinged bilobal structure with a single metal-binding site positioned between the two domains.
View Article and Find Full Text PDFKlebsiella pneumoniae is an opportunistic Gram-negative pathogen that is a leading cause of healthcare-associated infections, including pneumonia, urinary tract infections, and sepsis. Essential to the colonization and infection by K. pneumoniae is the acquisition of nutrients, such as the transition metal ion zinc.
View Article and Find Full Text PDFClinical isolates of the opportunistic pathogen from patients with cystic fibrosis (CF) frequently contain mutations in the gene encoding an elongation factor, FusA1. Recent work has shown that mutants often display elevated aminoglycoside resistance due to increased expression of the efflux pump, MexXY. However, we wondered whether these mutants might also be affected in other virulence-associated phenotypes.
View Article and Find Full Text PDFThe Gram-negative pathogen Pseudomonas aeruginosa is found ubiquitously within the environment and is recognised as an opportunistic human pathogen that commonly infects burn wounds and immunocompromised individuals, or patients suffering from the autosomal recessive disorder cystic fibrosis (CF). During chronic infection, P. aeruginosa is thought to form structured aggregates known as biofilms characterised by a self-produced matrix which encases the bacteria, protecting them from antimicrobial attack and the host immune response.
View Article and Find Full Text PDFThe macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically-infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity.
View Article and Find Full Text PDFOver the last two decades, tens of millions of dollars have been invested in understanding virulence in the human pathogen, Pseudomonas aeruginosa. However, the top 'hits' obtained in a recent TnSeq analysis aimed at identifying those genes that are conditionally essential for infection did not include most of the known virulence factors identified in these earlier studies. Instead, it seems that P.
View Article and Find Full Text PDFInternal reflection prisms were used to produce a narrow angular range of high reflectivity within a laser cavity. The selectivity was obtained from the sharp angular variation of internal reflectivity near the critical angle. Angular mode selection of a Nd: glass normal laser was achieved by this critical internal reflection (CIR) technique.
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