Identification of an Unusual Pattern of Global Gene Expression in Group B Streptococcus Grown in Human Blood

Because passage of the bacterium to blood is a crucial step in the pathogenesis of many group B Streptococcus (GBS) invasive infections, we recently conducted a whole-genome transcriptome analysis during GBS incubation ex vivo with human blood. In the current work, we sought to analyze in detail the difference in GBS gene expression that occurred in one blood sample (donor A) relative to other blood samples. We incubated GBS strain NEM316 with fresh heparinized human blood obtained from healthy volunteers, and analyzed GBS genome expression and cytokine production. Principal component analysis identified extensive clustering of the transcriptome data among all samples at time 0. In striking contrast, the whole bacterial gene expression in the donor A blood sample was significantly different from the gene expression in all other blood samples studied, both after 30 and 90 min of incubation. More genes were up-regulated in donor A blood relative to the other samples, at 30 min and 90 min. Furthermore, there was significant variation in transcript levels between donor A blood and other blood samples. Notably, genes with the highest transcript levels in donor A blood were those involved in carbohydrate metabolism. We also discovered an unusual production of proinflammatory and immunomodulatory cytokines: MIF, tPAI-1 and IL-1β were produced at higher levels in donor A blood relative to the other blood samples, whereas GM-CSF, TNF-α, IFN-γ, IL-7 and IL-10 remained at lower levels in donor A blood. Potential reasons for our observations are that the immune response of donor A significantly influenced the bacterial transcriptome, or both GBS gene expression and immune response were influenced by the metabolic status of donor A

Lateral gene transfer of streptococcal ICE element RD2 (region of difference 2) encoding secreted proteins

Background: The genome of serotype M28 group A Streptococcus (GAS) strain MGAS6180 contains a novel genetic element named Region of Difference 2 (RD2) that encodes seven putative secreted extracellular proteins. RD2 is present in all serotype M28 strains and strains of several other GAS serotypes associated with female urogenital infections. We show here that the GAS RD2 element is present in strain MGAS6180 both as an integrative chromosomal form and a circular extrachromosomal element. RD2-like regions were identified in publicly available genome sequences of strains representing three of the five major group B streptococcal serotypes causing human disease. Ten RD2-encoded proteins have significant similarity to proteins involved in conjugative transfer of Streptococcus thermophilus integrative chromosomal elements (ICEs). Results: We transferred RD2 from GAS strain MGAS6180 (serotype M28) to serotype M1 and M4 GAS strains by filter mating. The copy number of the RD2 element was rapidly and significantly increased following treatment of strain MGAS6180 with mitomycin C, a DNA damaging agent. Using a PCR-based method, we also identified RD2-like regions in multiple group C and G strains of Streptococcus dysgalactiae subsp.equisimilis cultured from invasive human infections. Conclusions: Taken together, the data indicate that the RD2 element has disseminated by lateral gene transfer to genetically diverse strains of human-pathogenic streptococci

GRB030406 an extremely hard burst outside of the INTEGRAL field of view

Using the IBIS Compton mode, the INTEGRAL satellite is able to detect and localize bright and hard GRBs, which happen outside of the nominal INTEGRAL telescopes field of view. We have developed a method of analyzing such INTEGRAL data to obtain the burst location and spectra. We present the results for the case of GRB030406. The burst is localized with the Compton events, and the location is consistent with the previous Interplanetary Network position. A spectral analysis is possible with the detailed modeling of the detector response for such a far off-axis source with the offset of 36.9 $^\circ$. The average spectrum of the burst is extremely hard: the photon index above 400 \kev is -1.7, with no evidence of a break up to 1.1 \mev at 90% confidence level.Comment: Astronomy and Astrophysics in pres

INTEGRAL upper limits on gamma-ray emission associated with the gravitational wave event GW150914

Using observations of the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL), we put upper limits on the gamma-ray and hard X-ray prompt emission associated with the gravitational wave event GW150914, discovered by the LIGO/Virgo collaboration. The omni-directional view of the INTEGRAL/SPI-ACS has allowed us to constrain the fraction of energy emitted in the hard X-ray electromagnetic component for the full high-probability sky region of LIGO trigger. Our upper limits on the hard X-ray fluence at the time of the event range from $F_{\gamma}=2 \times 10^{-8}$ erg cm$^{-2}$ to $F_{\gamma}=10^{-6}$ erg cm$^{-2}$ in the 75 keV - 2 MeV energy range for typical spectral models. Our results constrain the ratio of the energy promptly released in gamma-rays in the direction of the observer to the gravitational wave energy E$_\gamma/$E$_\mathrm{GW}<10^{-6}$. We discuss the implication of gamma-ray limits on the characteristics of the gravitational wave source, based on the available predictions for prompt electromagnetic emission.Comment: accepted for publication in ApJ

phiD12-Like Livestock-Associated Prophages Are Associated With Novel Subpopulations of Streptococcus agalactiae Infecting Neonates

Group B Streptococcus (GBS) is a major cause of invasive disease in neonates worldwide. Monitoring data have revealed a continuing trend toward an increase in neonatal GBS infections, despite the introduction of preventive measures. We investigated this trend, by performing the first ever characterization of the prophage content for 106 GBS strains causing neonatal infections between 2002 and 2018. We determined whether the genome of each strain harbored prophages, and identified the insertion site of each of the prophages identified. We found that 71.7% of the strains carried at least one prophage, and that prophages genetically similar to livestock-associated phiD12, carrying genes potentially involved in GBS pathogenesis (e.g., genes encoding putative virulence factors and factors involved in biofilm formation, bacterial persistence, or adaptation to challenging environments) predominated. The phiD12-like prophages were (1) associated with CC17 and 1 strains (p = 0.002), (2) more frequent among strains recovered during the 2011–2018 period than among those from 2002–2010 (p &lt; 0.001), and (3) located at two major insertion sites close to bacterial genes involved in host adaptation and colonization. Our data provide evidence for a recent increase in lysogeny in GBS, characterized by the acquisition, within the genome, of genetic features typical of animal-associated mobile genetic elements by GBS strains causing neonatal infection. We suggest that lysogeny and phiD12-like prophage genetic elements may have conferred an advantage on GBS strains for adaptation to or colonization of the maternal vaginal tract, or for pathogenicity, and that these factors are currently playing a key role in the increasing ability of GBS strains to infect neonates

The polarized gamma-ray burst GRB 061122

We report on the polarization measure, obtained with IBIS on board INTEGRAL, of the prompt emission of GRB 061122. Over an 8 s interval containing the brightest part of the gamma-ray burst (GRB) we put a lower limit on its polarization fraction of 60 per cent at 68 per cent confidence level (c.l.) and of 33 per cent at 90 per cent c.l. on the 250–800 keV energy range. We performed late time optical and near-infrared imaging observations of the GRB field using the Telescopio Nazionale Galileo and the Canada–France–Hawaii Telescope. Our multiband (ugrizYJHK) photometry allowed us to identify the host galaxy of GRB 061122 and to build its spectral energy distribution. Using a photometric redshift code we fitted these data, and derived the basic properties of the galaxy, including its type and redshift, that we could constrain to the interval [0.57, 2.10] at a 90 per cent c.l., with a best-fitting value of z = 1.33. The polarization measurement in different energy bands, together with the distance determination, allowed us to put the most stringent limit (ξ ≲ 3.4 × 10−16) to date to a possible Lorentz invariance violation based on the vacuum birefringence effect, predicted by some quantum-gravity theories

High Momentum Probes of Nuclear Matter

We discuss how the chemical composition of QCD jets is altered by final state interactions in surrounding nuclear matter. We describe this process through conversions of leading jet particles. We find that conversions lead to an enhancement of kaons at high transverse momentum in Au+Au collisions at RHIC, while their azimuthal asymmetry v_2 is suppressed.Comment: Contribution to the 4th international workshop High-pT physics at LHC 09, Prague; 6 pages, 6 figure