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Chlamydial MLST Site

A useful chlamydial multi locus typing site, with primers, is available here. The site is maintained by Yvonne Pannekoek (NL).

Sanger Sequencing: LGV Genome Sequences. Strain associated with European LGV outbreak is similar to the well known lab strains of LGV.

News Medical Net reports Jan 8 2008:

" Chlamydia is the most common treatable bacterial sexually transmitted disease worldwide, with around 90 million cases each year. As well as sexually transmitted disease (most often infections of the cervix or urogenital tract), it causes eye infection (trachoma), and also invasive disease called lymphogranuloma vernerum (LGV). Remarkably, these very different infections are caused by strains of Chlamydia that are very similar to one another.

"Chlamydia trachomatis has almost 900 genes and we found fewer than ten that differed significantly between the trachoma and the LGV strains," says Dr Nick Thomson from the Wellcome Trust Sanger Institute, who led the sequencing effort. "Some genes have decayed in the LGV strain, but the genes that are common to all are almost identical."

The study is published in the January 2008 issue of Genome Research by researchers from the Wellcome Trust Sanger Institute, the University of Southampton Medical School, Southampton HPA, University College Hospital, London and the University of California at Berkeley. Although the team found only a few sequence variants among the strains, they suggest that these key differences could provide new markers for improved diagnosis. For example, they confirmed that there were variants in each strain in a gene called Tarp that can be used to distinguish different isolates of LGV strains.

The most significant differences are thought to be those found in genes that alter the surface properties of Chlamydia, an organism that can replicate only inside host cells. To gain entry, Chlamydia must form close contact with the host cell and then trigger its uptake. Perhaps only two or three gene differences might markedly alter the ability of Chlamydia to prosper in different environments.

"Chlamydia are very difficult organisms to study in the laboratory and this, the first complete genome sequence for the invasive strain of Chlamydia trachomatis, will be of real value to research into and diagnosis of invasive Chlamydial infections," explains Professor Ian Clarke from the University of Southampton and senior author on the paper. "The gene catalogue will be of immediate use in designing studies to track Chlamydia and to understand the genes that cause these very different clinical consequences worldwide."

The researchers sequenced the genomes from two isolates of Chlamydia from patients with LGV - one obtained in California in the 1960s, and maintained as the major laboratory strain, and the other a recent isolate from a patient in London.

"The new sequences allow us to ask whether the recent increase in incidence of LGV is the result of emergence of a new and more virulent strain," continues Professor Clarke. "Our results suggest that the organism we find today is virtually identical with that isolated 40 years ago. It seems that we are not facing a novel, more dangerous organism."

The gene content of the two isolates is identical, with only around 500 differences between the two genomes. The research team found no evidence of novel genes or significant changes that might suggest a clear divergence between the two isolates. Only two changes, a small deletion and a single-letter change, are unique to the recent, London isolate.

Until recently, LGV was only rarely seen outside Africa or South-East Asia. However, in late 2004, more than 100 cases were reported in an outbreak in the Netherlands and, since that time, increasing numbers of cases have been seen in many countries. More than 400 cases were reported in the UK up to September 2006, in most cases among men who have sex with men.

"We found no evidence that this is a new epidemic isolate that is spreading worldwide," explains Dr Thomson. "Our results suggest that, far from being a novel and rapidly spreading form of Chlamydia, LGV is an old strain causing a new disease."

Chlamydia is, however, a wider health problem and accounts for 30 per cent of all new cases of sexually transmitted disease. Chlamydial infections are often symptomless for some time, increasing the chance of transmission. The UK Health Protection Agency suggested in November that "young sexually active adults should be screened for Chlamydia annually and after a partner change" because the highest at risk groups are young adults and gay men.

These genomes are the first to be published from the Wellcome Trust Sanger Institute using new-technology sequencing.

MEW adds: The group sequenced two isolates from the LGV biotype, a long-term laboratory passaged strain and the recent "epidemic" LGV isolate-causing proctitis. Although the genome of the epidemic LGV strain showed no additional genes that could account for the differences in disease outcome, they found evidence of functional gene loss and identified regions of heightened sequence variation that have previously been shown to be important sites for interstrain recombination. The recent epidemic LGV isolate causing an outbreak of proctitis in Europe is thought unlikely to be a newly emerged strain but is most probably an old strain with relatively new clinical manifestations.

Thomson, N. R. et al., (2008) Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates. Genome Research 18(1), 161 - 171 Epub 2007 Nov 21

  John Hopkins University gazette reports Jan 8 2008:

Sheila West, JHU, gets $10 million from Gates Foundation for Prevention of Trachoma.

The Partnership for the Rapid Elimination of Trachoma, or PRET, will be led by Sheila West of the Dana Center for Preventive Ophthalmology at the Wilmer Eye Institute at Johns Hopkins, in cooperation with the Johns Hopkins Center for Global Health. The partners include research teams at the university's School of Medicine and Bloomberg School of Public Health; the London School of Hygiene and Tropical Medicine; the University of California, San Francisco; Pfizer; the World Health Organization; and the Trachoma Control Programs at the ministries of health in Tanzania, Ethiopia and the Gambia.

The WHO has established a goal of fully controlling trachoma worldwide by 2020. The research conducted by PRET will help determine which prevention strategies and treatment interventions will be the most effective.

"No other research partnership has the breadth and ability to undertake such a comprehensive and critical proposal for trachoma control," said West, who is also a professor at the Johns Hopkins School of Medicine and holds a joint appointment at the Bloomberg School of Public Health.

The Gates Foundation grant will fund trials in two areas of trachoma control — surgery and antibiotics — in three countries hosting distinct infection scenarios: the Gambia, where the disease is on the verge of elimination; Tanzania, where treatment programs are in place, and the disease is on the decline; and Ethiopia, where treatment programs have not yet started.

The surgical phase of the study will examine the use of new devices to improve outcomes of surgery. Currently, mass treatment with an antibiotic is the WHO recommendation for trachoma- endemic communities. The antibiotic trials will address questions of how many persons in the community must be treated and how frequently treatment should occur to eliminate trachoma.

Pfizer, the private-sector partner in this consortium, has pledged sufficient antibiotics to country programs to control trachoma as part of the SAFE (surgery, antibiotics, facial cleanliness and environmental improvement) intervention. Antibiotics will also be provided for research needs.

"Trachoma disproportionately affects women and children in poor communities, and they often don't have a voice in priorities for health spending," West explained. "With this grant, we can target research to our trachoma control armamentarium and make better use of scarce resources and control strategies to alleviate blindness. None of us can do it on our own; we need to share the data among us to conquer the disease."

"The Johns Hopkins Center for Global Health is pleased to be able to facilitate and coordinate this extraordinary grant from the Bill & Melinda Gates Foundation," said Tom Quinn, the center's director. "This grant enables the center to help researchers and public health practitioners to control blinding trachoma, one of the great neglected tropical diseases affecting millions of people."

The Gates Foundation grant counts in the total of the Johns Hopkins Knowledge for the World campaign, which, as of Nov. 30, had raised more than $2.92 billion of its $3.2 billion goal. Priorities of the campaign, which benefits both The Johns Hopkins University and The Johns Hopkins Hospital and Health System, include strengthening endowment for student aid and faculty support; advancing research, academic and clinical initiatives; and building and upgrading facilities on all campuses. The campaign began in July 2000 and is scheduled to close at the end of 2008.  "

Chlamydophila psittaci and Chlamydophila pneumoniae found at high frequency in ocular swabs from trachoma patients in Nepal

An interesting paper (see link below) published online by Deborah Dean et al (2008) reports a study which looked for the presence of C. psittaci and C. pneumoniae in ocular swabs from trachoma patients in Nepal. 9 of 49 households in a trachoma endemic area of Nepal were selected and ocular swabs were probed with a real time, quantitative PCR for Chlamydiaceae species-specific ompA or 16S rRNA targets. Ocular and circulating IgG antibodies to Chlamydiaceae species-specific Hsp60 were also assessed. Surprisingly, all three species-C. trachomatis, Chlamydophila psittaci, and Chlamydophila pneumoniae-were detected in eight (89%) study households; one household had no members infected with C. pneumoniae. Of 80 (63%; n = 127) infected individuals, 28 (35%) had infection with C. psittaci, or C. pneumoniae, or both; single and dual infections with C. psittaci and C. pneumoniae were significantly associated with severe conjunctival inflammation (OR 4.25 [95% confidence interval (CI), 2.9-11.3], p = 0.009] as were single infections with C. trachomatis (OR 5.7 [95% CI, 3.8-10.1], p = 0.002). That the Chlamydophila infection was clinically significant is suggested by the finding that, of 80 (63%; n = 127) infected individuals, 28 (35%) had infection with C. psittaci, or C. pneumoniae, or both. Moreover, single and dual infections with C. psittaci and C. pneumoniae were significantly associated with severe conjunctival inflammation (OR 4.25 [95% confidence interval (CI), 2.9-11.3], p = 0.009] as were single infections with C. trachomatis (OR 5.7 [95% CI, 3.8-10.1], p = 0.002). Less surprisingly, the presence of tear antibody to Chlamydiaceae rHsp60 was also strongly correlated with infection and cicatricial scarring. The authors believe that ocular infection with Chlamydophila species was widespread and partly explains the failure to detect chlamydial infection using C. trachomatis specific tests in some patients with active trachoma. They also believe that C. psittaci and C. pneumoniae ocular infection can contribute to severe local inflammation and scarring. There will undoubtedly be much discussion about the primers used and these findings need to be confirmed in other trachoma endemic regions of the world. The full paper can be accessed on-line here.

Dean D, Kandel RP, Adhikari HK, Hessel T (2008) Multiple Chlamydiaceae Species in Trachoma: Implications for Disease Pathogenesis and Control. PLoS Med 5(1): e14 doi:10.1371/journal.pmed.0050014

Chlamydiae and the evolution of plant chloroplasts

I am grateful to Danielle Corsaro who, via the contact form, drew my attention to the paper of Tyra et al., 20007. These authors postulated that the re-targeting of existing host solute transporters to the plastid fore-runner must have been crucial for the early success of the primary endosymbiosis, allowing the host to harvest endosymbiont primary production. Accordingly they conducted a comprehensive analysis of the plastid permeome in the brassica, Arabidopsis thaliana, (Thale Cress) the first higher plant to have its genome sequenced.  Of 137 well-annotated transporter proteins that were initially considered, 83 that are broadly distributed in plants were submitted to phylogenetic analysis. The results indicated that 58% of Arabidopsis transporters, including all carbohydrate transporters, were of host origin, whereas only 12% arose from the cyanobacterial endosymbiont. However, four transporter genes were derived from a Chlamydiales-like source, suggesting that establishment of the primary plastid likely involved contributions from at least two prokaryotic sources. This therefore supports the hypothesis of Huang and Gogarten (2007) that important contributions in the evolution of the chloroplast came from the cyanobacterial endosymbiont and Protochlamydia-like bacteria co-resident in the first algae. For a newly updated article on this topic see chlamydiae and plastids.

Tyra, H. M., Linka, M., Weber, A. P. &  Bhattacharya, D. (2007). Host origin of plastid solute transporters in the first photosynthetic eukaryotes. Genome Biology Oct 5;8(10):R212. Full paper

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