Molecular, Epidemiological, and Clinical Complexities of Predicting Patterns of Infectious Diseases

The prediction of the future meets an essential need of humanity but it is not possible for the human epidemics. This need results in rites and “sciences ” such as haruspices (Etruscan reading the future in entrails of animals) and augurs (Romans reading the flight of birds). They are as old as the human history makes it possible to know. The scientific knowledge in astronomy gives the impression to be able to predict the events of the future thanks to observation of the events of the past. Thus astrology was initially developed by the astronomers such as Ptolemy, who, by their capability to predict the moon’s eclipses and the planets movements, were considered like magicians. This vision of the world still remains very vivid since XXV centuries and it is easy to see the echo of it, in all the countries of the world where astrology remains extraordinary prevalent. Concerning the epidemics, the temptation to predict the future is also important, even more so as politicians are accused of incompetence when an unexpected outbreak appears. This is linked with the reluctance to accept stochastic events. This brought about the development of mathematical models of epidemiology, of which none have been proven to be efficient, but that influenced the human society in a considerable way through the media. Among the examples for which we are involved are mad cow disease (which was predicted to cause hundreds of thousands of deaths), the prediction on evolution of the epidemic of AIDS (that was contradicted by a rapid decline in Africa in the middle of the 90th), the avian influenza (which predicted that the virus was going to be transformed into an agent of inter-human disease), the dramatic decline of Malaria in Africa (that was unpredicted), and, finally, the recent episode on the swine flu. This episode of A-H1N1 “swine flu” pandemics highlighted the scope of our ignorance by associating elements which had never been seen in the pandemic or seasonal flu (Nougairede et al., 2010)

Defining Pathogenic Bacterial Species in the Genomic Era

Actual definitions of bacterial species are limited due to the current criteria of definition and the use of restrictive genetic tools. The 16S ribosomal RNA sequence, for example, has been widely used as a marker for phylogenetic analyses; however, its use often leads to misleading species definitions. According to the first genetic studies, removing a certain number of genes from pathogenic bacteria removes their capacity to infect hosts. However, more recent studies have demonstrated that the specialization of bacteria in eukaryotic cells is associated with massive gene loss, especially for allopatric endosymbionts that have been isolated for a long time in an intracellular niche. Indeed, sympatric free-living bacteria often have bigger genomes and exhibit greater resistance and plasticity and constitute species complexes rather than true species. Specialists, such as pathogenic bacteria, escape these bacterial complexes and colonize a niche, thereby gaining a species name. Their specialization allows them to become allopatric, and their gene losses eventually favor reductive genome evolution. A pathogenic species is characterized by a gene repertoire that is defined not only by genes that are present but also by those that are lacking. It is likely that current bacterial pathogens will disappear soon and be replaced by new ones that will emerge from bacterial complexes that are already in contact with humans

The rhizome of Reclinomonas americana, Homo sapiens, Pediculus humanus and Saccharomyces cerevisiae mitochondria

<p>Abstract</p> <p>Background</p> <p>Mitochondria are thought to have evolved from eubacteria-like endosymbionts; however, the origin of the mitochondrion remains a subject of debate. In this study, we investigated the phenomenon of chimerism in mitochondria to shed light on the origin of these organelles by determining which species played a role in their formation. We used the mitochondria of four distinct organisms, <it>Reclinomonas americana</it>, <it>Homo sapiens</it>, <it>Saccharomyces cerevisiae </it>and multichromosome <it>Pediculus humanus</it>, and attempted to identify the origin of each mitochondrial gene.</p> <p>Results</p> <p>Our results suggest that the origin of mitochondrial genes is not limited to the <it>Rickettsiales </it>and that the creation of these genes did not occur in a single event, but through multiple successive events. Some of these events are very old and were followed by events that are more recent and occurred through the addition of elements originating from current species. The points in time that the elements were added and the parental species of each gene in the mitochondrial genome are different to the individual species. These data constitute strong evidence that mitochondria do not have a single common ancestor but likely have numerous ancestors, including proto-<it>Rickettsiales</it>, proto-<it>Rhizobiales </it>and proto-<it>Alphaproteobacteria</it>, as well as current alphaproteobacterial species. The analysis of the multichromosome <it>P. humanus </it>mitochondrion supports this mechanism.</p> <p>Conclusions</p> <p>The most plausible scenario of the origin of the mitochondrion is that ancestors of <it>Rickettsiales </it>and <it>Rhizobiales </it>merged in a proto-eukaryotic cell approximately one billion years ago. The fusion of the <it>Rickettsiales </it>and <it>Rhizobiales </it>cells was followed by gene loss, genomic rearrangements and the addition of alphaproteobacterial elements through ancient and more recent recombination events. Each gene of each of the four studied mitochondria has a different origin, while in some cases, multichromosomes may allow for enhanced gene exchange. Therefore, the tree of life is not sufficient to explain the chimeric structure of current genomes, and the theory of a single common ancestor and a top-down tree does not reflect our current state of knowledge. Mitochondrial evolution constitutes a rhizome, and it should be represented as such.</p> <p>Reviewers</p> <p>This article was revised by William Martin, Arcady Mushegian and Eugene V. Koonin.</p

Questions on Mediterranean Spotted Fever a Century after Its Discovery

New findings in MSF epidemiology, clinical features, and severe forms have changed the general perception of MSF

SVARAP and aSVARAP: simple tools for quantitative analysis of nucleotide and amino acid variability and primer selection for clinical microbiology

BACKGROUND: Simple computerized methods that analyse variability along alignments of nucleotide or amino acid sequences can be very useful in a clinical microbiology laboratory for two main purposes. First, to optimize primer selection, which is critical for the identification of infectious pathogens based on gene sequencing: primers must target conserved nucleotide regions bordering highly variable areas to ensure discrimination of species. Second, it can be of interest to reveal mutations associated with drug resistance of pathogen agents. Our aim was therefore to test easy and cost-free tools (SVARAP and aSVARAP) that require short hands-on work, little expertise, and which allow visual interpretation and statistical analysis of results. RESULTS: We first tested SVARAP to improve a strategy of identification of streptococci species of the Viridans Group targeting the groESL gene. Two regions with <500 nucleotides were identified, one being significantly more discriminant than one of a similar length used in a previous study (mean number of nucleotide differences between species, 113 (range: 12–193) vs. 77 (range: 14–109); p < 10(-3)). Secondly, aSVARAP was tested on reverse transcriptase (RT) sequences from 129 HIV-1 clinical strains to identify natural polymorphisms and drug-selected mutations emerging under nucleoside RT inhibitor (NRTI)-selective pressure. It revealed eleven of the 18 RT mutations considered in a reference HIV-1 genotypic NRTI-resistance interpretation algorithm. CONCLUSION: SVARAP and aSVARAP are simple, versatile and helpful tools for analysis of sequence variability, and are currently being used in real practice in our clinical microbiology laboratory

Bartonella quintana Characteristics and Clinical Management

The pathogen is reemerging in the United States and Europe and is responsible for a number of clinical conditions