β‑Lactam Biotransformations Activate Innate Immunity

Antibiotics are widely prescribed to treat bacterial infections, but many of these drugs also affect patient immune responses. While the molecular mechanisms regulating these diverse immunomodulatory interactions are largely unknown, recent studies support two primary models: (1) antibiotics can alter immune function by directly interacting with human targets; and/or (2) antibiotics can indirectly affect immune responses via alteration of the human microbiota composition. Here, we describe results that could support a third model in which a nonimmunostimulatory antibiotic can be biotransformed by human microbiota members into an immunostimulatory product that lacks antibacterial activity. Specifically, we identified, characterized, and semisynthesized new biotransformation products derived from the β-lactams amoxicillin and ampicillin, antibiotics regularly prescribed in the clinic. The drug metabolism products were identified in bacterial cultures harboring β-lactamase, a common resistance determinant. One of the amoxicillin biotransformation products activated innate immunity, as assessed by NF-κB signaling in human leukemic monocytes, whereas amoxicillin itself exhibited no effect. Amoxicillin has previously been shown to have minimal long-term impact on human microbiota composition in clinical trial studies. Taken together, our results could support a broader immunomodulatory mechanism whereby antibiotics could indirectly regulate immune function in a stable, microbiome-dependent manner

MOESM2 of Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo

Additional file 2. Neighbour-joining tree of samples from DRC, Benin and Senegal, produced in Figtree ( http://tree.bio.ed.ac.uk/software/figtree/ ). Edges are coloured from red to blue according to their bootstrap percentage (black edges are terminal and so have no bootstrap value). Dotted lines leading away from the tree are coloured to indicate the origin of the sample

Additional file 1: of Molecular characterization of invasive meningococcal isolates in Burkina Faso as the relative importance of serogroups X and W increases, 2008–2012

(PDF) Unrooted phylogeny of international NmW CC11 isolates. The 128 isolates from this study are identified by black squares, the Hajj-related outbreak isolate is identified by a black star, and the remaining 470 isolates are identified according to the categories defined by from Lucidarme et al. [23]. Arrows mark isolates that are not in the same category as the most closely related isolates: the Hajj-related outbreak isolate (M07149) and an “Anglo/French Hajj strain” isolate collected in France during 2014 (M14 240,446). The tree is scaled by the number of parsimonious substitutions per branch, identified by kSNP3. Branches with bootstrap support < 70% have been deleted. (PDF 33 kb

MOESM1 of Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia

Additional file 1. Ex vivo drug susceptibility of P. vivax by years