抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.

Clostridium difficile infection.

The increasing prevalence of antibiotic-resistant bacteria is a global threat to public health. Agricultural use of antibiotics is believed to contribute to the spread of antibiotic resistance, but the mechanisms by which many agricultural practices influence resistance remain obscure. Although manure from dairy farms is a common soil amendment in crop production, its impact on the soil microbiome and resistome is not known. To gain insight into this impact, we cultured bacteria from soil before and at 10 time points after application of manure from cows that had not received antibiotic treatment. Soil treated with manure contained a higher abundance of β-lactam–resistant bacteria than soil treated with inorganic fertilizer. Functional metagenomics identified β-lactam– resistance genes in treated and untreated soil, and indicated that the higher frequency of resistant bacteria in manure-amended soil was attributable to enrichment of resident soil bacteria that harbor β-lactamases. Quantitative PCR indicated that manure treatment enriched the blaCEP-04 gene, which is highly similar (96%) to a gene found previously in a Pseudomonas sp. Analysis of 16S rRNA genes indicated that the abundance of Pseudomonas spp. increased in manure-amended soil. Populations of other soil bacteria that commonly harbor β-lactamases, including Janthinobacterium sp. and Psychrobacter pulmonis, also increased in response to manure treatment. These results indicate that manure amendment induced a bloom of certain antibiotic-resistant bacteria in soil that was independent of antibiotic exposure of the cows from which the manure was derived. Our data illustrate the unintended consequences that can result from agricultural practices, and demonstrate the need for empirical analysis of the agroecosystem.

https://www.pnas.org/content/pnas/111/42/15202.full.pdf

Bloom of resident antibiotic-resistant bacteria in soil following manure fertilization

Part I: Isolation of Bacteriophages 1. Isolation of Bacteriophages for Fastidious Bacteria Shigenobu Matsuzaki, Jumpei Uchiyama, Iyo Takemura-Uchiyama, Takako Ujihara, and Masanori Daibata 2. Isolation of Bacteriophages of the Anaerobic Bacteria Bacteroides Cristina Garcia-Aljaro, Maite Muniesa, and Juan Jofre 3. Isolation of Bacteriophages for Clinically Relevant Bacteria Sanna Sillankorva Part II: Characterization of Bacteriophages 4. In Vitro Activity against Planktonic and Biofilm Populations Assessed by Flow Cytometry Luis Melo, Diana Priscila Pires, and Joana Azeredo 5. Observation of Bacteriophage Ultrastructure by Cryo-electron Microscopy Ana Cuervo and Jose L. Carrascosa 6. Bacteriophage Taxonomy: an Evolving Discipline Igor Tolstoy, Andrew M. Kropinski, and J. Rodney Brister Part III: Bacteriophage Selection and Cocktail Formulation 7. Determination of the Bacteriophage Host Range - Culture Based Approach Andrey V. Letarov, and Eugene E. Kulikov 8. Recovery and Characterization of Bacteria Resisting Infection by Lytic Bacteriophage Libera Latino and Christine Pourcel 9. Guidelines to Compose an Ideal Bacteriophage Cocktail Maia Merabishvili, Jean-Paul Pirnay, and Daniel De Vos Part IV: Biodistribution, Host Interaction and Clinical Application 10. Interaction of Bacteriophages with Mammalian Cells Zuzanna Kazmierczak and Krystyna Dabrowska 11. In Vivo Bacteriophage Biodistribution Nicolas Dufour, Raphaelle Delattre, and Laurent Debarbieux 12. Interaction of Bacteriophages with the Immune System: Induction of Bacteriophage-specific Antibodies Krystyna Dabrowska & nbsp 13. Bacteriophage Treatment of Infected Diabetic Foot Ulcers Vera V. Morozova, Yulia N. Kozlova, Denis A. Ganichev, and Nina V. Tikunova 14. Compassionate Use of Bacteriophage Therapy for Foot Ulcer Treatment as an Effective Step for Moving Toward Clinical Trials Randolph Fisha, Elizabeth Kutter, Gordon Wheat, Bob Blasdel, Mzia Kutateladze, and Sarah Kuhl Part V: Production, Purification and Bacteriophage Storage 15. Bacteriophage Production in Bioreactors Maryam Agboluaje and Dominic Sauvage 16. Computational Modelling of Bacteriophage Production for Process Optimization Konrad Krysiak-Baltyn and Sally L. Gras 17. Methods for Bacteriophage Preservation Malgorzata B. Lobocka, Aleksandra Glowacka, and Piotr Golec Part VI: Safety and Regulation 18. Bacteriophage Production in Compliance with Regulatory Requirements Jean-Paul Pirnay, Maia Merabishvili, Hilde Van Raemdonck, Daniel De Vos, and Gilbert Verbeken 19. Guidelines for Bacteriophage Product Certification Alan Fauconnier Part VII: New Phage Therapy Approaches 20. Nano/micro Formulations for Bacteriophage Delivery Pilar Cortes, Mary Cano-Sarabia, Joan Colom, Jennifer Otero, Daniel Maspoch, and Montserrat Llagostera 21. Synthetic Biology to Engineer Bacteriophage Genomes Ana Rita Costa, Catarina Milho, Joana Azeredo, and Diana Priscila Pires

Bacteriophage therapy : from lab to clinical practice

Pseudomonas putida bacteremia in adult patients: five case reports and a review of the literature

We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America.

Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007.

Clostridium difficile flagellin stimulates toll-like receptor 5, and toxin B promotes flagellin-induced chemokine production via TLR5

OBJECTIVE Thrombocytopenia is frequently observed during bloodstream infection (BSI); however, little is known about the trends in platelet size during BSI. The aim of this study was to investigate trends in platelet indices during BSI and to determine the relationship between the mean platelet volume (MPV) levels and the prognosis of BSI patients. METHODS We conducted a four-year retrospective study to assess the trends in the platelet indices and the clinical features of BSI. We enrolled 350 patients with positive blood cultures and measured the platelet indices during five periods: 30 to seven days before onset (1st period); within one day of onset (2nd period); three to five days after onset (3rd period); seven to 10 days after onset (4th period); and 14 to 19 days after onset (5th period). The end point was defined as 30-day mortality. RESULTS Among the BSI patients, the average platelet count decreased during BSI (29.4 *10(9)/L to 24.0 *10(9)/L, p<0.001), while the average MPV level increased (7.33 fL to 7.89 fL, p<0.001). The degree of MPV elevation in the nonsurvivors (n=25) was lower than that observed in the survivors (n=325) between the 1st and 2nd periods (0.00 fL vs. 0.35 fL, p=0.006), whereas between the 2nd and 3rd periods, the degree of MPV elevation in the nonsurvivors was higher than that observed in the survivors (0.74 fL vs. 0.19 fL, p=0.03). MPV elevation after BSI was identified to be a negative prognostic factor for BSI (odds ratio: 1.82; 95% confidence interval: 1.00-3.32; p=0.027). CONCLUSION Changes in the MPV levels after BSI may therefore be a useful prognostic marker for BSI.

Changes in the mean platelet volume levels after bloodstream infection have prognostic value

Objectives 
Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels during infection and their associations with other clinical factors. The aim of this study was to assess the time course of endocan levels and the associations of endocan with clinical factors during infection by comparison with other biomarkers.


Methods 
Serum samples and blood cultures were obtained from patients who were diagnosed with infection from June 2013 to March 2014. Serum endocan, C-reactive protein (CRP), and procalcitonin (PCT) levels during four periods during infection were measured (day 0, day 1-2, day 3-5, and day 6-10).


Results 
A total of 78 patients were enrolled in this study. The median endocan level decreased by only 23% during infection, whereas both serum CRP and PCT levels decreased by more than 80%. Endocan levels were correlated to neither CRP levels nor PCT levels in each period. Endocan levels at day 0 in patients with bacteremia were higher than those without bacteremia (1.09 ng/mL vs 0.82 ng/mL, P=0.002), but neither CRP levels nor PCT levels at day 0 were different between the two groups. Areas under the receiver operator characteristic (ROC) curves of endocan, CRP, and PCT at day 0 were 0.662, 0.343, and 0.563, respectively. Positive blood cultures tended to be related to high endocan levels, but not significantly (odds ratio: 4.24, 95% CI: 0.99-10.34, P=0.05).


Conclusions 
In bacteremic cases, serum endocan levels in bacteremia tended to be higher than in non-bacteremic cases. Although endocan level was not identified as a prognostic factor of bacteremia, further prospective study concerning the relationship between serum endocan level and bacteremia would be needed.

/pdf/characteristics-of-serum-endocan-levels-in-infection-2tr2nag1oh.pdf

Yusuke Yoshino

Papers

Pseudomonas putida bacteremia in adult patients: five case reports and a review of the literature

Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007.

Clostridium difficile flagellin stimulates toll-like receptor 5, and toxin B promotes flagellin-induced chemokine production via TLR5

Changes in the mean platelet volume levels after bloodstream infection have prognostic value

Characteristics of Serum Endocan Levels in Infection