MicrobiologyBytes

Streptococcus pneumoniae is the leading bacterial cause of pneumonia, sepsis and meningitis in children, which together comprise more than 25% of the 10 million deaths estimated to have occurred in 2000 in children under 5 years of age, and preventable by access to appropriate vaccines. The serotypes currently included in existing pneumococcal conjugate vaccine formulations account for 49-88% of deaths in children under 5 in Africa and Asia, where the morbidity and mortality of pneumococcal disease are the highest, and where until recently, most children do not have access to current pneumococcal conjugate vaccines.

Contrary to current thinking, the group of serotypes of S. pneumoniae responsible for most invasive pneumococcal disease worldwide is conserved across regions. After an extensive literature review, which included information on 60,090 isolates of Streptococcus pneumoniae from 70 countries, the authors of a new paper estimate that seven serotypes (1, 5, 6A, 6B, 14, 19F, and 23F) were the most common globally and that these seven serotypes accounted for the majority of invasive pneumococcal disease in every region.

This is good news. These findings mean that health policy makers can assess the potential impact of serotypes included in different conjugate vaccines and vaccine manufacturers can now work from a consensus set of serotype coverage estimates to plan and design future serotype-based vaccine formulations to target local pneumococcal disease burden more accurately. Progress towards increasing access to pneumococcal conjugate vaccines in high-burden countries will contribute to achieving the year 2015 Millennium Development Goal 4 target to reduce child mortality by two-thirds.

Systematic Evaluation of Serotypes Causing Invasive Pneumococcal Disease among Children Under Five: The Pneumococcal Global Serotype Project. (2010) PLoS Med 7(10): e1000348. doi:10.1371/journal.pmed.1000348
Background: Approximately 800,000 children die each year due to pneumococcal disease and .90% of these deaths occur in developing countries where few children have access to life-saving serotype-based vaccines. Understanding the serotype epidemiology of invasive pneumococcal disease (IPD) among children is necessary for vaccine development and introduction policies. The aim of this study was to systematically estimate the global and regional distributions of serotypes causing IPD in children ,5 years of age.
Methods and Findings: We systematically reviewed studies with IPD serotype data among children, 5 years of age from the published literature and unpublished data provided by researchers. Studies conducted prior to pneumococcal conjugate vaccine (PCV) introduction, from 1980 to 2007, with 12 months of surveillance, and reporting 20 serotyped isolates were included. Serotype-specific proportions were pooled in a random effects meta-analysis and combined with PD incidence and mortality estimates to infer global and regional serotype-specific PD burden. Of 1,292, studies reviewed, 169 were included comprising 60,090 isolates from 70 countries. Globally and regionally, six to 11 serotypes accounted for 70% of IPD. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) were the most common globally; and based on year 2000 incidence and mortality estimates these seven serotypes accounted for 300,000 deaths in Africa and 200,000 deaths in Asia. Serotypes included in both the 10- and 13-valent PCVs accounted for 10 million cases and 600,000 deaths worldwide.
Conclusions: A limited number of serotypes cause most IPD worldwide. The serotypes included in existing PCV formulations account for 49%–88% of deaths in Africa and Asia where PD morbidity and mortality are the highest, but few children have access to these life-saving vaccines.

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• Specific pneumococcus serotypes associated with increased mortality
• New Insights Could Lead to a Better Pneumococcal Vaccine
• Germ Warfare

The recent identification of retrovirus XMRV and a second retrovirus of a different subtype in chronic fatigue syndrome has aroused much interest, not least among sufferers. However, it remains highly controversial whether the detection of these viruses represents true infection or laboratory artifacts. In this paper, Professor Robin Weiss, the UK’s leading authority on retroviruses, gives his critical appraisal of this confusing data and concludes:

A cautionary tale of virus and disease. BMC Biology 2010, 8: 124 doi:10.1186/1741-7007-8-124

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Fungi reproduce both sexually and asexually, producing a vast array of structures which have evolved over time to suit habitat and in some cases host. These structures are of great economic importance to society. Approximately 48% of the world’s food crop yield is lost due to plant diseases, of which the majority are caused by fungi. For most fungal diseases, the primary sources of inoculum are sexual and/or asexual spores. As well as economic losses, fungi can have positive economic benefits for agriculture, such as biocontrol of plant diseases. Numerous fungi have been successfully developed as biocontrol agents (BCAs) of plant diseases and the majority of these are sold as spore preparations.

The global fungal BCA market is dominated by species of the ubiquitous ascomycete Trichoderma. In general, commercial preparations of Trichoderma spp. for biological control consist of bulk-produced conidia (asexual spores), but good biocontrol activity in the environment relies upon the fungus remaining vegetative, and thus antagonistically active. The ideal Trichoderma BCA produces ample conidia in a cost-effective manner during production and maintains long periods of vigorous vegetative growth during usage. Understanding the factors that control this morphogenic switch from mycelia to conidia is integral to biocontrol research. Over 50 years of studies on conidiation in the genus have established Trichoderma as a model for asexual reproduction in fungi. This review presents what is known about the physiological responses of Trichoderma to the environmental cues that induce conidiation, and provides insights into the molecular basis of these responses, including an examination of the signal transduction pathways which link environmental signals to physiological outputs. Understanding species-specific differences in metabolic adaptations to the environment should assist biocontrol design and implementation. Knowledge of the appropriate conditions for maximal yields of viable spores would likely reduce production costs. Knowledge of survivability and vigour within a complex environment could enable targeting of biocontrol strains to the soil or foliar condition appropriate for their species. It may also be possible to create designer BCAs which incorporate desired traits through protoplast fusion or genetic modification.

Reproduction without sex: conidiation in the filamentous fungus Trichoderma. Microbiology 2010 156: 2887-2900
Trichoderma spp. have served as models for asexual reproduction in filamentous fungi for over 50 years. Physical stimuli, such as light exposure and mechanical injury to the mycelium, trigger conidiation; however, conidiogenesis itself is a holistic response determined by the cell’s metabolic state, as influenced by the environment and endogenous biological rhythms. Key environmental parameters are the carbon and nitrogen status and the C:N ratio, the ambient pH and the level of calcium ions. Recent advances in our understanding of the molecular biology of this fungus have revealed a conserved mechanism of environmental perception through the White Collar orthologues BLR-1 and BLR-2. Also implicated in the molecular regulation are the PacC pathways and the conidial regulator VELVET. Signal transduction cascades which link environmental signals to physiological outputs have also been revealed.

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• Bacterial endophytes
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Polymyxins are the last resort in the therapy of infections caused by extremely multiresistant Gram-negative bacteria. However, their nephrotoxicity may complicate the therapy or even require its discontinuation. Whether new derivatives are less toxic in relevant animal models in vivo than older polymyxins remains to be seen. The future will also show whether resistance to polymyxins will evolve to limit their use. The use of polymyxin compounds in combination with another antibiotic may reduce the risk of resistance developing. We need to be very careful with our remaining drugs of last resort.

Polymyxins and their novel derivatives. Curr Opin Microbiol. Sep 23 2010
The emerging very multiresistant Gram-negative bacteria cause remarkable therapeutic challenges. There are no novel classes of agents in clinical development for the treatment of Gram-negative infections. Polymyxins such as polymyxin B and colistin were abandoned in the seventies but are now back in the therapy as the last resort. Their nephrotoxicity may complicate the therapy or even necessitate its discontinuation. Less toxic polymyxin derivatives would be highly welcome. Novel derivatives lack in strategic positions two of the five cationic charges of polymyxins, differ from polymyxins in their renal handling and affinity to kidney brush-border membrane, and are in preclinical studies. Less characterized other recent derivatives, also reviewed here, have increased the collective knowledge on the structure-function relationships in polymyxins. Acquired resistance to polymyxins has been encountered. However, the resistance mechanism compromises the function of the bacterial outer membrane as a permeability barrier to other noxious agents.

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• Designer drugs for discerning bugs. PNAS USA September 27 2010,. doi: 10.1073/pnas.101254710
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