Whipple's disease: a macrophage disease.
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Actinomycetales↗
Biomedical subjects
Didier Raoult
Publications and source records attributed to Didier Raoult.
Evaluation of sedimentation rate, rheumatoid factor, C-reactive protein, and tumor necrosis factor for the diagnosis of infective endocarditis.
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Biomarkers↗
Murine model of infection by Tropheryma whipplei.
We developed an animal model reproducing several aspects of Whipple's disease. Immunocompetent mice were persistently infected with Tropheryma whipplei, its etiological agent, and developed liver granulomas. SCID mice were infected similarly but did not develop tissue lesions. The delayed clearance of T. whipplei suggests a protective role for innate immunity.
Actinomycetales↗
Role for the CD28 molecule in the control of Coxiella burnetii infection.
Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular bacterium that replicates in macrophages. As cell-mediated immune response to microbial pathogens requires signals mediated by T-cell receptors and costimulatory molecules such as CD28, we wondered if CD28 is involved in protection against C. burnetii infection. CD28-deficient (CD28-/-) mice were inoculated with C. burnetii by intraperitoneal and intravenous routes. With both wild-type and CD28-/- mice, C. burnetii organisms were detected exclusively in spleen and liver. The antibody response against C. burnetii was impaired in CD28-/- animals, but, surprisingly, the lack of CD28 decreased C. burnetii burden in the infected tissues, whatever the manner of inoculation of bacteria. The CD28 deficiency had no effect on either granuloma formation, which reflects cell-mediated immunity against C. burnetii, or the production of gamma interferon and tumor necrosis factor, two cytokines known to be involved in granuloma formation. On the other hand, the production of interleukin-10 (IL-10) by peritoneal macrophages was highly impaired in CD28-/- mice. The results suggest that CD28 initiates a signal that favors C. burnetii replication through the modulation of the IL-10 pathway.
Animals↗
Global transcriptome analysis of Tropheryma whipplei in response to temperature stresses.
Tropheryma whipplei, the agent responsible for Whipple disease, is a poorly known pathogen suspected to have an environmental origin. The availability of the sequence of the 0.92-Mb genome of this organism made a global gene expression analysis in response to thermal stresses feasible, which resulted in unique transcription profiles. A few genes were differentially transcribed after 15 min of exposure at 43 degrees C. The effects observed included up-regulation of the dnaK regulon, which is composed of six genes and is likely to be under control of two HspR-associated inverted repeats (HAIR motifs) found in the 5' region. Putative virulence factors, like the RibC and IspDF proteins, were also overexpressed. While it was not affected much by heat shock, the T. whipplei transcriptome was strongly modified following cold shock at 4 degrees C. For the 149 genes that were differentially transcribed, eight regulons were identified, and one of them was composed of five genes exhibiting similarity with genes encoding ABC transporters. Up-regulation of these genes suggested that there was an increase in nutrient uptake when the bacterium was exposed to cold stress. As observed for other bacterial species, the major classes of differentially transcribed genes encode membrane proteins and enzymes involved in fatty acid biosynthesis, indicating that membrane modifications are critical. Paradoxically, the heat shock proteins GroEL2 and ClpP1 were up-regulated. Altogether, the data show that despite the lack of classical regulation pathways, T. whipplei exhibits an adaptive response to thermal stresses which is consistent with its specific environmental origin and could allow survival under cold conditions.
Actinomycetales↗
Multispacer typing to study the genotypic distribution of Bartonella henselae populations.
Bartonella henselae, a worldwide fastidious bacterium, has a feline reservoir and is pathogenic for humans. However, the relationship between human and cat isolates of B. henselae, as well as its population dynamics and geographic heterogeneity, is not fully understood, in part because of the absence of appropriate typing methods. Multilocus sequence typing (MLST), the most discriminatory genotyping method for B. henselae, identified seven genotypes and suggested that human isolates arose from a limited number of cat isolates. Herein, we estimated the discriminatory power of multispacer typing (MST) by studying 126 B. henselae cat isolates from various areas of Europe, Asia, and the United States. We identified the nine most variable intergenic spacers conserved by both B. henselae and Bartonella quintana genomes. By comparing the sequences obtained from these nine spacers for each studied isolate, we identified 39 MST genotypes. The distribution of isolates into MST genotypes matched their phylogenetic organization into four clusters. MST showed that European and Asian isolates were different, in contrast with American isolates, but failed to identify pandemic strains. Our study demonstrated that MST is a powerful method for genotyping B. henselae at the strain level and may serve in studying the population dynamics of this bacterium and understanding the relationships between cat and human isolates. Finally, we provide a free-access MST-Rick online software program (http://ifr48.timone.univ-mrs.fr/MST_BHenselae/mst) that investigators may use to compare their own MST sequences to our database.
Animals↗
Mycobacterium barrassiae sp. nov., a Mycobacterium moriokaense group species associated with chronic pneumonia.
Three identical isolates of new rapidly growing mycobacteria (RGM) were recovered from the bronchial aspirate and sputum from a 49-year-old woman presenting with lung lesions. The case met the American Thoracic Society criteria for the diagnosis of nontuberculous mycobacterial infection. The three isolates grew in 3 days at 24 to 42 degrees C. The 16S rRNA gene sequence analysis indicated that the sequences of the isolates were identical and shared 99.7% and 98.1% similarities with those of Mycobacterium moriokaense and Mycobacterium gadium, respectively. Partial 723-bp rpoB sequence analyses indicated that the sequences of the isolates shared 95.8% and 92.3% similarities with those of M. moriokaense and M. gadium, respectively. Polyphasic identification (including biochemical tests; antimicrobial susceptibility profiling; and hsp65, recA, and sodA gene sequence analyses, as well as G+C content determination and cell wall fatty acid composition analysis) supported the evidence that these isolates were representative of a new species. Phylogenetic analyses confirmed the close relationships of the isolates with M. moriokaense and the defined M. moriokaense group. These isolates were susceptible to the antimicrobials currently recommended for the treatment of RGM infections. These isolates differed from M. moriokaense by their susceptibility to vancomycin. We propose the name Mycobacterium barrassiae sp. nov. for this new species. The type strain is N7T (CIP 108545T and CCUG 50398T).
Anti-Bacterial Agents↗
Genetic differentiation of Chinese isolates of Rickettsia sibirica by partial ompA gene sequencing and multispacer typing.
Current data on rickettsiae and rickettsial diseases in China remain limited. Using partial ompA gene sequencing and multispacer typing, we identified 15 rickettsial isolates from China. All isolates were found to belong to Rickettsia sibirica subsp. sibirica. Four isolates from Dermacentor sinicus collected in Beijing, China, were fully identical to strain BJ-90, previously demonstrated to belong to R. sibirica subsp. sibirica despite antigenic and genotypic specificities. All 11 remaining isolates were similar to the R. sibirica subsp. sibirica type strain, 246. These were widely distributed in China in humans and different tick species. We emphasize the importance of surveying the distribution of R. sibirica in China.
Animals↗
First isolation of Bartonella alsatica from a valve of a patient with endocarditis.
We report the first documented case of endocarditis in a man infected with Bartonella alsatica, which causes bacteremia in healthy wild rabbits. B. alsatica was identified by serology and culture and by PCR of an aortic valve specimen. B. alsatica should be added to the list of zoonotic agents of blood culture-negative endocarditis.
Aged↗
Endocarditis caused by Cardiobacterium valvarum.
A fastidious, gram-negative bacterium was isolated from the blood of a 51-year-old man who had acute infectious endocarditis (IE). Characterization of the organism through phenotypic and genotypic analyses revealed the causative role of Cardiobacterium valvarum. This is the third reported case of IE caused by C. valvarum.
Cardiobacterium↗
Analysis of 525 samples to determine the usefulness of PCR amplification and sequencing of the 16S rRNA gene for diagnosis of bone and joint infections.
The 16S rRNA gene PCR in the diagnosis of bone and joint infections has not been systematically tested. Five hundred twenty-five bone and joint samples collected from 525 patients were cultured and submitted to 16S rRNA gene PCR detection of bacteria in parallel. The amplicons with mixed sequences were also cloned. When discordant results were observed, culture and PCR were performed once again. Bacteria were detected in 139 of 525 samples. Culture and 16S rRNA gene PCR yielded identical documentation in 475 samples. Discrepancies were linked to 13 false-positive culture results, 5 false-positive PCR results, 9 false-negative PCR results, 16 false-negative culture results, and 7 mixed infections. Cloning and sequencing of 16S rRNA gene amplicons in 6 of 8 patients with mixed infections identified 2 to 8 bacteria per sample. Rarely described human pathogens such as Alcaligenes faecalis, Comamonas terrigena, and 21 anaerobes were characterized. We also detected, by 16S rRNA gene PCR, four previously identified bacteria never reported in human infection, Alkanindiges illinoisensis, dehydroabietic acid-degrading bacterium DhA-73, unidentified Hailaer soda lake bacterium, and uncultured bacterium clone HuCa4. Seven organisms representing new potential species were also detected. PCR followed by cloning and sequencing may help to identify new pathogens involved in mixed bone infection.
Arthritis, Infectious↗
Sequencing of the rpoB gene and flanking spacers for molecular identification of Acinetobacter species.
Acinetobacter species are defined on the basis of several phenotypic characters, results of DNA-DNA homology, and more recently, similarities or dissimilarities in 16S rRNA gene sequences. However, the 16S rRNA gene is not polymorphic enough to clearly distinguish all Acinetobacter species. We used an RNA polymerase beta-subunit gene (rpoB)-based identification scheme for the delineation of species within the genus Acinetobacter, and towards that end, we determined the complete rpoB gene and flanking spacer (rplL-rpoB and rpoB-rpoC) sequences of the 17 reference strains of Acinetobacter species and 7 unnamed genomospecies. By using complete gene sequences (4,089 bp), we clearly separated all species and grouped them into different clusters. A phylogenetic tree constructed using these sequences was supported by bootstrap values higher than those obtained with 16S rRNA or the gyrB or recA gene. Four pairs of primers enabled us to amplify and sequence two highly polymorphic partial sequences (350 and 450 bp) of the rpoB gene. These and flanking spacers were designed and tested for rapid identification of the 17 reference strains of Acinetobacter species and 7 unnamed genomospecies. Each of these four variable sequences enabled us to delineate most species. Sequences of at least two polymorphic sequences should be used to distinguish Acinetobacter grimontii, Acinetobacter junii, Acinetobacter baylyi, and genomic species 9 from one another. Finally, 21 clinical isolates of Acinetobacter baumannii were tested for intraspecies relationships and assigned correctly to the same species by comparing the partial sequences of the rpoB gene and its flanking spacers.
Acinetobacter↗
Description of Mycobacterium conceptionense sp. nov., a Mycobacterium fortuitum group organism isolated from a posttraumatic osteitis inflammation.
A nonpigmented rapidly growing mycobacterium was isolated from wound liquid outflow, bone tissue biopsy, and excised skin tissue from a 31-year-old woman who suffered an accidental open right tibia fracture and prolonged stay in a river. The three isolates grew in 3 days at 24 to 37 degrees C. 16S rRNA sequence analyses over 1,483 bp showed that they were identical and shared 99.7% (4-bp difference) sequence similarity with that of Mycobacterium porcinum, the most closely related species. Partial rpoB (723 bp) sequence analyses showed that the isolates shared 97.0% sequence similarity with that of M. porcinum. Further polyphasic approaches, including biochemical tests, antimicrobial susceptibility analyses, and hsp65, sodA, and recA gene sequence analysis, as well as % G+C determination and cell wall fatty acid composition analysis supported the evidence that these isolates were representative of a new species. Phylogenetic analyses showed the close relationship with M. porcinum in the Mycobacterium fortuitum group. The isolates were susceptible to most antibiotics and exhibited evidence for penicillinase activity, in contrast to M. porcinum. We propose the name Mycobacterium conceptionense sp. nov. for this new species associated with posttraumatic osteitis. The type strain is D16(T) (equivalent to CIP 108544(T) and CCUG 50187(T)).
Adult↗
Characterization of mimivirus DNA topoisomerase IB suggests horizontal gene transfer between eukaryal viruses and bacteria.
Mimivirus, a parasite of Acanthamoeba polyphaga, is the largest DNA virus known; it encodes dozens of proteins with imputed functions in nucleic acid transactions. Here we produced, purified, and characterized mimivirus DNA topoisomerase IB (TopIB), which we find to be a structural and functional homolog of poxvirus TopIB and the poxvirus-like topoisomerases discovered recently in bacteria. Arginine, histidine, and tyrosine side chains responsible for TopIB transesterification are conserved and essential in mimivirus TopIB. Moreover, mimivirus TopIB is capable of incising duplex DNA at the 5'-CCCTT cleavage site recognized by all poxvirus topoisomerases. Based on the available data, mimivirus TopIB appears functionally more akin to poxvirus TopIB than bacterial TopIB, despite its greater primary structure similarity to the bacterial TopIB group. We speculate that the ancestral bacterial/viral TopIB was disseminated by horizontal gene transfer within amoebae, which are permissive hosts for either intracellular growth or persistence of many present-day bacterial species that have a type IB topoisomerase.
Acanthamoeba↗
Etiological diagnosis of blood-culture-negative endocarditis.
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Antibodies, Bacterial↗
A century of rickettsiology: emerging, reemerging rickettsioses, clinical, epidemiologic, and molecular diagnostic aspects and emerging veterinary rickettsioses: an overview.
This overview summarize the salient features of advances in the epidemiology, vectors, and clinical and laboratory diagnoses of rickettsiology. Presentations on veterinary rickettsiology highlight the importance of the rickettsiae in animal husbandry.
Animals↗
Ecology and molecular epidemiology of tick-borne rickettsioses and anaplasmoses with natural foci in Russia and Kazakhstan.
During our more than 20 years of monitoring, we have used epidemiological, field, and experimental methods for characterization of natural foci of tick-borne rickettsioses in Russia. The main results were obtained through genetic methods (PCR sequence) at the Université de la Mediterranée (Marseille, France). We describe considerable heterogeneity of tick-borne alpha(1)-proteobacteria: 16 microorganisms the of the order Rickettsiales were detected in Russia and Kazakhstan. R. sibirica-caused North Asiatic tick-borne rickettsiosis is the main tick-borne rickettsiosis in Russia, with wide distribution in Siberia and the Russian Far East and high epidemic activity of natural foci of different landscape types. Our results show circulation of different pathogenic rickettsiae in the same endemic territories. In the Far East region, R. sibirica subsp. R. sibirica, R. sibirica subsp. BJ-90, and R. heilongjiangensis were detected; in the Altay and Krasnojarsk regions, R. sibirica subsp. R. sibirica and R. heilongjiangensis; and in the Kurgan district of West Siberia, R. sibirica subsp. R. sibirica and R. slovaca. The roles of more than 15 new genotypes of alpha(1)-proteobacteria in infectious disease in Russia and Kazakhstan are in need of further study.
Anaplasma↗
Far eastern tick-borne rickettsiosis: identification of two new cases and tick vector.
We recently reported the first documented cases of a new rickettsial disease caused by Rickettsia heilongjiangensis in the Russian Far East (Far Eastern tick-borne rickettsiosis). Here we report the amplification of DNA of R. heilongjiangensis from both the skin biopsy of an acutely ill patient and the tick removed from him prior to the disease development. The tick has been identified as Haemaphysalis spp. The clinical picture was that of a spotted fever group rickettsiosis and a seroconversion was noted with R. heilongjiangensis antigen. Screening testing of both species of Haemaphysalis ticks inhabiting Russian Far Eastern regions showed that up to 28.13% of H. concinnae and 4.48% of H. japonica douglasii ticks harbor R. heilongjiangensis. It has been concluded that H. concinnae may serve as the main vector for the transmission of R. heilongjiangensis. H. japonica douglasii ticks harbor several varieties of rickettsiae. DNA of "Candidatus Rickettsia tarasevichiae," previously found in Ixodes persulcatus ticks, was amplified from one male tick. Two sequenced complete gltA genes belong to the novel spotted fever group rickettsial species provisionally called here "Candidatus Rickettsia principis" variants Hjd54 and Hjd61. The rate of infection has been found to be not higher than 1.5%.
Adult↗