Keep an ear out for Francisella tularensis: otomastoiditis Cases after Canyoneering

We report here three unusual cases of otomastoiditis due to Francisella tularensis, complicated by cervical abscesses and persistent hearing loss, plus facial paralysis for one patient. Intriguingly, the three patients had practiced canyoneering independently in the same French river, between 2009 and 2014, several days before clinical symptoms onset. The results point out that fresh water exposure may be a potential contamination route for tularemia. Besides, due to the frequent complications and sequelae, we believe that F. tularensis should be considered as a possible etiology in case of otitis media, failure of the conventional antibiotic treatment, and suspicious exposure of the bacteria

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Bacterial factors involved in infective endocarditis occurrence during Staphylococcus aureus bacteremia

L'endocardite infectieuse (EI) est une complication rare mais gravissime de la bactériémie à Staphylococcus aureus. Bien que certains facteurs de risque liés à l'hôte aient été décrits, l'implication de facteurs bactériens dans la survenue de l'EI est encore inconnue. Ces travaux de thèse ont visé à chercher tout élément bactérien associé à l'EI. Les facteurs phénotypiques décrits ou supposés comme potentiellement impliqués dans l'EI ont été testés. En parallèle, les profils génotypiques des souches obtenus par puces ADN ont été analysés par différents outils statistiques. L'analyse statistique univariée n'a montré aucune différence significative entre souches d'EI et souches de bactériémie, suggérant un processus complexe et multifactoriel. En effet, l'analyse discriminante en composante principale appliquée sur les données de puces ADN a permis de mettre en évidence une distinction entre les deux groupes de souches, confirmée sur une collection indépendante de souches. De plus, une fonction linéaire simplifiée, basée sur seulement 8 marqueurs génétiques, a permis d'obtenir des performances similaires, sur la collection de souches initiale ainsi que la collection indépendante de validation. En dernier lieu, les souches d'EI et de bactériémie ont été comparées à partir de séquences du génome complet (n = 40 (20 EI, 20 bactériémies)). L'analyse statistique par analyse discriminante en composante principale réalisée sur ces données génomiques confirme une distinction possible entre les deux groupes de souches. Au total, ces travaux de thèse apportent la preuve de concept que les facteurs bactériens sont impliqués dans la survenue de l'EI au cours de bactériémie à S. aureusInfective endocarditis (IE) is a severe condition complicating 10-25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. This PhD work aimed to characterize strictly defined IE and bacteremia isolates and searched for discriminant features. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed. No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses, suggesting a multifactorial process. However, the discriminant analysis of principal components (DAPC), applied on microarray data, segregated IE and bacteremia isolates. The performance of this model was confirmed with an independent collection of IE and bacteremia isolates. Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection and in the independent validation collection. At last, IE and bacteremia isolates were compared based on whole genome sequence data from a subset of 40 isolates. When applied to this dataset, DAPC confirmed a possible segregation between the two groups of isolates. All in all, this PhD work provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremi

Unexpected severe native aortic subacute endocarditis due to Bartonella quintana in a 40-year-old woman with good socioeconomic condition

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Limitations of staphylokinase as a marker for Staplylococcus aureus invasive infections in humans

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The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation

International audienceType IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of Neisseria meningitidis, the causative agent of cerebrospinal meningitis, are involved in the colonization of human nasopharynx. After invasion of the bloodstream, Tfp allow adhesion of N. meningitidis to human endothelial cells, which leads to the opening of the blood-brain barrier and meningitis. To achieve firm adhesion, N. meningitidis induces a host cell response that results in elongation of microvilli surrounding the meningococcal colony. Here we study the role of the major pilin subunit PilE during host cell response using human dermal microvascular endothelial cells and the pharynx carcinoma-derived FaDu epithelial cell line. We first show that some PilE variants are unable to induce a host cell response. By engineering PilE mutants, we observed that the PilE C-terminus domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and that hypervariable regions confer different host cell specificities. Moreover, the study of point mutants of the pilin D-region combined with structural modeling of PilE revealed that the D-region contains two independent regions involved in signaling to human dermal microvascular endothelial cells (HDMECs) or FaDu cells. Our results indicate that the diversity of the PilE D-region sequence allows the induction of the host cell response via several receptors. This suggests that Neisseria meningitidis has evolved a powerful tool to adapt easily to many niches by modifying its ability to interact with host cells. IMPORTANCE Type IV pili (Tfp) are long appendages expressed by many Gram-negative bacteria, including Neisseria meningitidis, the causative agent of cerebrospinal meningitis. These pili are involved in many aspects of pathogenesis: natural competence, aggregation, adhesion, and twitching motility. More specifically, Neisseria meningitidis, which is devoid of a secretion system to manipulate its host, has evolved its Tfp to signal to brain endothelial cells and open the blood-brain barrier. In this report, we investigate, at the molecular level, the involvement of the major pilin subunit PilE in host cell response. Our results indicate that the PilE C-terminal domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and contains two independent regions involved in host cell signaling