345 research outputs found
Peptide occurring in Enterobacteriaceae triggers Streptococcus pneumoniae cell death
No full textNonencapsulated Streptococcus pneumoniae often possess two genes, aliB-like ORF 1 and aliB-like ORF 2, in place of capsule genes. AliB-like ORF 1 is thought to encode a substrate binding protein of an ABC transporter which binds peptide SETTFGRDFN, found in 50S ribosomal subunit protein L4 of Enterobacteriaceae.
Here, we investigated the effect of binding of AliB-like ORF 1 peptide on the transcriptome and proteome of nonencapsulated pneumococci. We found upregulation of gene expression of a metacaspase and a gene encoding N-acetylmuramoyl-L-alanine amidase, both of which are proposed to be involved in programmed cell death in prokaryotic cells. Proteome profiling indicated upregulation of transcriptional regulators and downregulation of metabolism-associated genes. Exposure to the peptide specifically triggered death in pneumococci which express AliB-like ORF 1, with the bacteria having an apoptotic appearance by electron microscopy. We propose that binding of the AliB-like ORF 1 peptide ligand by the pneumococcus signals a challenging environment with hostile bacterial species leading to death of a proportion of the pneumococcal population
Genomic and functional analysis of emerging virulent and multidrug-resistant Escherichia coli lineage sequence type 648
No full textThe pathogenic extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli lineage ST648 is increasingly reported from multiple origins. Our study of a large and global ST648 collection from various hosts (87 whole-genome sequences) combining core and accessory genomics with functional analyses and in vivo experiments suggests that ST648 is a nascent and generalist lineage, lacking clear phylogeographic and host association signals. By including large numbers of ST131 (n = 107) and ST10 (n = 96) strains for comparative genomics and phenotypic analysis, we demonstrate that the combination of multidrug resistance and high-level virulence are the hallmarks of ST648, similar to international high-risk clonal lineage ST131. Specifically, our in silico, in vitro, and in vivo results demonstrate that ST648 is well equipped with biofilm-associated features, while ST131 shows sophisticated signatures indicative of adaption to urinary tract infection, potentially conveying individual ecological niche adaptation. In addition, we used a recently developed NFDS (negative frequency-dependent selection) population model suggesting that ST648 will increase significantly in frequency as a cause of bacteremia within the next few years. Also, ESBL plasmids impacting biofilm formation aided in shaping and maintaining ST648 strains to successfully emerge worldwide across different ecologies. Our study contributes to understanding what factors drive the evolution and spread of emerging international high-risk clonal lineages.Katharina Schaufler, Torsten Semmler, Lothar H. Wieler, Darren J. Trott, Johann Pitout, Gisele Peirano, Jonas Bonnedahl, Monika Dolejska, Ivan Literak, Stephan Fuchs, Niyaz Ahmed, Mirjam Grobbel, Carmen Torres, Alan McNally, Derek Pickard, Christa Ewers, Nicholas J. Croucher, Jukka Corander, Sebastian Guenthe
Women, work and war : industrial mobilisation and demobilisation, Coventry and Bolton, 1940-1946
No full textThe emphasis in this thesis is on women's popular
attitudes towards the two processes of industrial mobilisation
and demobilisation which took place between 1940 and 1946.
Although the work includes a survey of the national picture of
those two processes, it concentrates on case studies in two towns
which exhibited different characteristics of women's employment,
Coventry and Bolton. This is done in an attempt to see if the
tradition of women's employment affected their attitudes towards
war work. In Coventry, the best sources of women's employment
were for single women. During the nineteen-thirties it was obvious
that the motor industry employed increasing numbers of women, but, again,
the unmarried. The economic participation rate in Coventry was slightly
lower than the national average. On the other hand, the cotton industry
in Bolton customarily had engaged married women as well as single women,
therefore, the women's economic participation rate was about 10 per cent.
higher than the national average. Local custom with regard to married
women's employment appears to have affected women's ideas About their
domestic responsibilities. Coventry women were more reserved and more
conscious of their domestic role. However, the comparison between the
two towns also brought out similarities as well as differences in women's
attitudes to industrial mobilisation. During demobilisation, the
similarities between Coventry and Bolton were more strongly marked.
The majority of women war workers had no intention of staying on in the
factory, in jobs which were still largely thought of as 'men's work'.
Most women thought that their well-being was dependent on men's secure
employment and high wages. They did not want to do anything to threaten
it. There seems to have been little antagonism between men and women
during the mobilisation and demobilisation period
Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing
No full textChlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b
Whole genome alignments of 15 sequence clusters of similar isolates
No full textFifteen FASTA format whole genome alignments, each corresponding to one of the monophyletic sequence clusters identified through population clustering and phylogenetics as described in Croucher et al (2013) Nat. Genet. 45:656-663. Alignments were generated through mapping of paired Illumina reads to a reference sequence, itself omitted from the alignment, using SMALT. Files are compressed as a single archive using tar and gzip
Evidence for several waves of global transmission in the seventh cholera pandemic.
No full textVibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic. Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 can cause epidemic cholera. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae
Control and Filtering for Discrete Linear Repetitive Processes with H infty and ell 2--ell infty Performance
No full textRepetitive processes are characterized by a series of sweeps, termed passes, through a set of dynamics defined over a finite duration known as the pass length. On each pass an output, termed the pass profile, is produced which acts as a forcing function on, and hence contributes to, the dynamics of the next pass profile. This can lead to oscillations which increase in amplitude in the pass to pass direction and cannot be controlled by standard control laws. Here we give new results on the design of physically based control laws for the sub-class of so-called discrete linear repetitive processes which arise in applications areas such as iterative learning control. The main contribution is to show how control law design can be undertaken within the framework of a general robust filtering problem with guaranteed levels of performance. In particular, we develop algorithms for the design of an H? and dynamic output feedback controller and filter which guarantees that the resulting controlled (filtering error) process, respectively, is stable along the pass and has prescribed disturbance attenuation performance as measured by and – norms
Immune interface interference vaccines: An evolution‐informed approach to anti‐bacterial vaccine design
No full textAbstract Developing protein‐based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti‐bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high‐throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, ‘immune interface interference’ (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H‐binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein‐based vaccines to prevent bacterial infections
Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine
No full textStreptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design
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