A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study

SummaryBackground The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. Methods On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. Findings Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. Interpretation Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. Funding The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG)

Temporal dynamics of microbiota before and after host death

The habitats that animals, humans and plants provide for microbial communities are inevitably transient, changing drastically when these hosts die. Because microbes associated with living hosts are ensured prime access to the deceased host's organic matter, it is feasible that opportunistic, adaptable lifestyles are widespread among host-associated microbes. Here we investigate the temporal dynamics of microbiota by starving to death a host-the planktonic Crustacean Daphnia magna-and tracking the changes in its microbial community as it approaches death, dies and decomposes. Along with obligate host-associated microbes that vanished after the host's death and decomposers that appeared after the host's death, we also detected microbes with opportunistic lifestyles, seemingly capable of exploiting the host even before its death. We suggest that the period around host death plays an important role for host-microbiota ecology and for the evolution of hosts and their microbes

Impact of scaffold rigidity on the design and evolution of an artificial Diels-Alderase

By combining targeted mutagenesis, computational refinement, and directed evolution, a modestly active, computationally designed Diels-Alderase was converted into the most proficient biocatalyst for [4+2] cycloadditions known. The high stereoselectivity and minimal product inhibition of the evolved enzyme enabled preparative scale synthesis of a single product diastereomer. X-ray crystallography of the enzyme-product complex shows that the molecular changes introduced over the course of optimization, including addition of a lid structure, gradually reshaped the pocket for more effective substrate preorganization and transition state stabilization. The good overall agreement between the experimental structure and the original design model with respect to the orientations of both the bound product and the catalytic side chains contrasts with other computationally designed enzymes. Because design accuracy appears to correlate with scaffold rigidity, improved control over backbone conformation will likely be the key to future efforts to design more efficient enzymes for diverse chemical reactions

Catalytic Stimulation by Restrained Active-Site Floppiness—The Case of High Density Lipoprotein-Bound Serum Paraoxonase-1

Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, combined with empirical valence bond simulations, reveal a network of hydrogen bonds that connect HDL binding residues with Asn168-a key catalytic residue residing &gt;15 angstrom from the HDL contacting interface. This network ensures precise alignment of N168, which, in turn, ligates PON1's catalytic calcium and aligns the lactone substrate for catalysis. HDL binding restrains the overall motion of the active site and particularly of N168, thus reducing the catalytic activation energy barrier. We demonstrate herein that disturbance of this network, even at its most far-reaching periphery, undermines PON1's activity. Membrane binding thus immobilizes long-range interactions via second- and third-shell residues that reduce the active site's floppiness and pre-organize the catalytic residues. Although this network is critical for efficient catalysis, as demonstrated here, unraveling these long-rage interaction networks is challenging, let alone their implementation in artificial enzyme design.</p

Vers un ailleurs prometteur…

Les migrations sont-elles une réponse universelle à une situation de crise ? Poser cette question ouvre sans doute le plus vaste débat sur l’histoire du mouvement des hommes. Cet ouvrage illustre bien la diversité et la multiplicité de cette incroyable richesse qu'est le mouvement des hommes et des peuples sur notre planète. Tout changement est un déséquilibre et, réciproquement, ce sont les déséquilibres qui permettent le changement. Est-il possible d’anticiper, dès lors, sur le futur ? Peut-on imaginer ce que sera demain la grande mouvance des peuples ? Engendrera-t-elle autant de peurs que d’innovations ? Comme le prévisage Albert Jacquard, les migrations de masse sont des catastrophes. Ainsi, “préparer demain”, nécessite des changements fondamentaux dans nos “visions du monde” politiques, économiques et sociales tout autant que dans notre mode d’exploitation des ressources naturelles.HERMANN-MICHEL HAGMANN Secrétaire général Laboratoire de démographie économique et sociale Université de Genève JEAN-LUC MAURER Directeur Institut universitaire d'études du développement Genèv

Global spatiotemporal dynamics of Mycoplasma pneumoniae re-emergence after COVID-19 pandemic restrictions : an epidemiological and transmission modelling study

Abstract: Background Mycoplasma pneumoniae is a major cause of respiratory tract infections. We aimed to investigate the spatiotemporal dynamics, antimicrobial resistance, and severity of the delayed re-emergence of infections with M pneumoniae after the implementation of non-pharmaceutical interventions (NPIs) against COVID-19. Methods Epidemiological data (positive and total test numbers, and macrolide-resistant M pneumoniae detections) and clinical data (hospitalisations, intensive care unit [ICU] admissions, and deaths) were collected through our global surveillance from April 1, 2017 to March 31, 2024. The moving epidemic method (MEM) was used to establish epidemic periods, and the time-series susceptible\u2013infected\u2013recovered (TSIR) model to investigate the delayed re-emergence. Findings The dataset included 65 sites in 29 countries from four UN regions: Europe, Asia, the Americas, and Oceania. A global re-emergence of M pneumoniae cases by PCR detection was noted from the second half of 2023. The mean global detection rate was 11\ub747% (SD 15\ub782) during the re-emergence (April, 2023\u2013March, 2024). By use of MEM, the re-emergence was identified as epidemic in all four UN regions, simultaneously in ten countries at calendar week 40 (early October, 2023). Macrolide-resistant M pneumoniae rates from Europe and Asia were 2\ub702% and 71\ub722%, respectively, and did not differ between the re-emergence and pre-COVID-19 pandemic periods. During the re-emergence, some countries reported increased hospitalisations (in adults, two of ten countries; and in children, two of 14 countries) and ICU admissions (in adults, one of nine countries; and in children, two of 14 countries). Overall, 65 (0\ub711%) deaths were reported, without statistical difference between pre-COVID-19 pandemic and re-emergence. The TSIR model accurately predicted, considering a 3-week generation time of M pneumoniae and a 90% reduction in transmission through NPIs, the observed delayed re-emergence. Interpretation This large global dataset for M pneumoniae detections shows that although there was an unprecedented high number of detections across many countries in late 2023, the severity and number of deaths remained low. Our results suggest that the delayed re-emergence was related to the long incubation period of M pneumoniae infection