The volatile microbiome

The first detailed temporal study of the human microbiome shows that individual body habitats exhibit surprising variation over time yet maintain distinguishable community structures

Emerging view of the human virome

The human virome is the collection of all viruses that are found in or on humans, including both eukaryotic and prokaryotic viruses. Eukaryotic viruses clearly have important effects on human health, ranging from mild, self-limited acute or chronic infections to those with serious or fatal consequences. Prokaryotic viruses can also influence human health by affecting bacterial community structure and function. Therefore, definition of the virome is an important step toward understanding how microbes affect human health and disease. We review progress in virome analysis, which has been driven by advances in high-throughput, deep sequencing technology. Highlights from these studies include the association of viruses with clinical phenotypes and description of novel viruses that may be important pathogens. Together these studies indicate that analysis of the human virome is critical as we aim to understand how microbial communities influence human health and disease. Descriptions of the human virome will stimulate future work to understand how the virome affects long-term human health, immunity, and response to coinfections. Analysis of the virome ultimately may affect the treatment of patients with a variety of clinical syndromes

Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

AbstractPathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, Treponema paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections

Host genetic control of gut microbiome composition.

The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05-0.45), indicating that 5-45% of inter-individual variation can be explained by genetics. Through twin studies, genetic association studies, systems genetics, and genome-wide association studies (GWAS), hundreds of specific host genetic loci have been shown to associate with the abundance of discrete gut microbes. Using genetically engineered knock-out mice, at least 30 specific genes have now been validated as having specific effects on the microbiome. The relationships among of host genetics, microbiome composition, and abundance, and disease is now beginning to be unraveled through experiments designed to test causality. The genetic control of disease and its relationship to the microbiome can manifest in multiple ways. First, a genetic variant may directly cause the disease phenotype, resulting in an altered microbiome as a consequence of the disease phenotype. Second, a genetic variant may alter gene expression in the host, which in turn alters the microbiome, producing the disease phenotype. Finally, the genetic variant may alter the microbiome directly, which can result in the disease phenotype. In order to understand the processes that underlie the onset and progression of certain diseases, future research must take into account the relationship among host genetics, microbiome, and disease phenotype, and the resources needed to study these relationships

The recA protein of E. coli : regulation and function in recombination and repair : UV induction, autoregulatory model, DNA binding protein, DNA renaturation, strand assimilation

In Escherichia coli, the recA function is required for general recombination, repair of DNA damage and a diverse group of functions which are coordinately expressed following DNA damage or arrest of DNA synthesis (SOS functions ). These latter functions include UV mutagenesis, W- reactivation of damaged phage DNA, prophage induction and cell filamentation. In this paper we summarize experiments which have elucidated regulatory and functional aspects of the recA gene product. Biochemical and genetic data suggest a model for control of recA gene expression in which the recA protein auto regulates its own synthesis following UV irradiation or other forms of DNA damage. The features of this autoregulatory mechanism are different from those proposed for gene 32 protein of phage T4. Biochemical experiments with homogeneous wild type and mutant forms of RecA protein reveal that this unique DNA binding protein catalyzes DNA renaturation and single strand assimilation reactions which are coupled to ATP hydrolysis. These results indicate that RecA protein catalyzes strand transfer during the initiation of genetic recombination and during post-replication repair of damaged DNA in vivo.KEVIN MCENTEE AND GEORGE M. WEINSTOCK, Department of Biochemistry, Stanford University School of Medicine, Stanford, California

Genome analysis of a highly virulent serotype 1 strain of streptococcus pneumoniae from West Africa

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, estimated to cause 2 million deaths annually. The majority of pneumococcal mortality occurs in developing countries, with serotype 1 a leading cause in these areas. To begin to better understand the larger impact that serotype 1 strains have in developing countries, we characterized virulence and genetic content of PNI0373, a serotype 1 strain from a diseased patient in The Gambia. PNI0373 and another African serotype 1 strain showed high virulence in a mouse intraperitoneal challenge model, with 20% survival at a dose of 1 cfu. The PNI0373 genome sequence was similar in structure to other pneumococci, with the exception of a 100 kb inversion. PNI0373 showed only15 lineage specific CDS when compared to the pan-genome of pneumococcus. However analysis of non-core orthologs of pneumococcal genomes, showed serotype 1 strains to be closely related. Three regions were found to be serotype 1 associated and likely products of horizontal gene transfer. A detailed inventory of known virulence factors showed that some functions associated with colonization were absent, consistent with the observation that carriage of this highly virulent serotype is unusual. The African serotype 1 strains thus appear to be closely related to each other and different from other pneumococci despite similar genetic content