Elizabethkingia anophelis outbreak in France.

OBJECTIVE: We report an outbreak of Elizabethkingia anophelis infections in France. To the best of our knowledge, this is the first outbreak described in Europe. METHODS: Each E. anophelis-positive microbiological sample was considered a case. All patients were hospitalized in an infectious diseases unit. Clinical, environmental, and microbiological investigations (MALDI-TOF mass spectrometry, PCR, E-test) were performed for each case. RESULTS: Twenty cases were reported from September 2020 to September 2021, mainly community-acquired infections, responsible for nine deaths. The phylogenetic analysis showed a clonal origin and excluded nosocomial transmission. Despite the analysis of multiple environmental specimens, no source of contamination was identified. All strains were highly resistant to cefotaxime, ceftazidime, and imipenem. CONCLUSIONS: Clinicians and microbiologists should be aware of this multidrug-resistant bacterium, capable of causing severe infections. Most strains showed the lowest minimum inhibitory concentration values for cotrimoxazole and ciprofloxacin, making them the best choice for empirical antibiotic therapy.

Accuracy of gradient diffusion method for susceptibility testing of dalbavancin and comparators.

OBJECTIVES: This multicenter study aimed to assess the performances of gradient diffusion (GD) method in comparison to broth microdilution (BMD) method for susceptibility testing of dalbavancin, daptomycin, vancomycin, and teicoplanin. METHODS: Minimum Inhibitory Concentrations (MICs) were retrospectively determined concomitantly by BMD and GD methods, for 93 staphylococci and enterococci isolated from clinical samples. BMD was considered as the gold standard. Essential (EA) and categorical agreements (CA) were calculated. Discordant categorical results were categorized as major (ME) and very major errors (VME). RESULTS: EA and CA were 95.7% and 96.8%, 82.8% and 100%, 97.8% and 96.8%, and 94.6% and 95.7% for dalbavancin, daptomycin, vancomycin, and teicoplanin respectively. Concerning dalbavancin, 3 ME without any VME were observed and discrepancies were low (≤ to 2 two-fold dilutions) between both methods. VME were noted in 1 and 3 cases for vancomycin and teicoplanin, respectively, and resulted from 1 two-fold dilution discrepancy in each case. EA was lower for daptomycin. When they were discrepant, BMD MICs were systematically higher than GD ones. Nevertheless, no categorical discrepancy was noted. CONCLUSIONS: GD appears as an acceptable and convenient alternative for dalbavancin, vancomycin, and teicoplanin MICs determination. Our study also emphasizes how achieving accurate daptomycin MICs remains challenging.

Secondary structure determination of 15N-labelled human Long-[Arg-3]-insulin-like growth factor 1 by multidimensional NMR spectroscopy.

Insulin-like growth factors (IGFs) are a group of proteins that promote cell growth and differentiation. Long-[Arg-3]-IGF-I (Francis et al. (1992) J. Mol. Endocrinol. 8, 213-223), a potent analogue of IGF-I, which has a Glu-3 to Arg-3 substitution and a hydrophobic, thirteen amino acid N-terminal extension, has been studied by 1H,15N NMR spectroscopy. All the backbone 1H and 15N assignments and most of the 1H sidechain assignments have been completed. The secondary structure elements were identified by determining the sequential and medium range NOEs from sensitivity-enhanced 15N-NOESY-HSQC and sensitivity-enhanced 15N-HSQC-NOESY-HSQC spectra. The IGF-I domain of Long-[Arg-3]-IGF-I was found to have an almost identical structure to IGF-I. The N-terminal seven amino acid residues of the extension have very few medium range or long range NOEs but the next five amino acids form a turn-like structure that is spatially close to the beginning of helix 1 in the IGF-I domain. Hydrogen-deuterium exchange experiments show that all the slowly exchanging backbone amide protons in the IGF-I domain are either in the helical or the extended structural elements. Many of the amide protons in the N-terminal extension are also protected from the solvent although the residues in this part of the extension do not have any identifiable secondary structure. The results are interpreted in terms of the increased biological potency of Long-[Arg-3]-IGF-I and the decreased binding to insulin-like growth factor binding proteins.

Solution conformation of bovine lens alpha- and betaB2-crystallin terminal extensions.

alpha- and betaB2-Crystallin are the major proteins in the mammalian lens. Each of these crystallins has short, flexible terminal extensions from its domain core; the two alpha-crystallin subunits have C-terminal extensions of eight and ten amino acids whilst betaB2-crystallin has N- and C-terminal extensions of 15 and 11 amino acids, respectively. The solution conformations of these chemically synthesised extensions have been examined by two-dimensional 1H NMR spectroscopy. The N-terminal extension of betaB2-crystallin and the C-terminal extensions of alpha-crystallin adopt little ordered structure. In the membrane-mimicking solvent trifluoroethanol, the alpha-crystallin extensions are also unstructured. In contrast, the C-terminal extension of betaB2-crystallin in water has a structural preference towards turn-like structures, creating a hydrophobic region involving G198, F200 and P202. In the lens, the C-terminal extension of betaB2-crystallin is the only one of these extensions that interacts to any large extent with other crystallins. The structural preference of the C-terminal extension of betaB2-crystallin may therefore have implications for the role of this extension in crystallin-crystallin interactions.