OXA-1 β-lactamase and non-susceptibility to penicillin/β-lactamase inhibitor combinations among ESBL-producing Escherichia coli

Background ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related to co-production of OXA-1 penicillinase. Methods During a national study we collected 293 ESBL-producing E. coli from bacteraemias, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results The collection was dominated by ST131 (n = 188 isolates, 64.2%) and bla CTX-M-15 (present in 229 isolates, 78.2%); over half the isolates (159/293, 54.3%) were ST131 with bla CTX-M-15. bla OXA-1 was found in 149 ESBL producers (50.9%) and bla TEM-1/191 in 137 (46.8%). Irrespective of whether all isolates were considered, or ST131 alone, there were strong associations (P < 0.001) between co-carriage of bla OXA-1 and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of bla TEM-1/191. For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of bla OXA-1 to 8 or 16 mg/L in its presence; for co-amoxiclav the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. bla OXA-1 was strongly associated with co-carriage also of aac(6′)-Ib-cr, which compromises amikacin and tobramycin. Conclusions Co-carriage of OXA-1, a penicillinase with weak affinity for inhibitors, is a major correlate of resistance to piperacillin/tazobactam and co-amoxiclav in E. coli and is commonly associated with co-carriage of aac(6′)-Ib-cr, which narrows aminoglycoside options

Investigation of Plasmon Resonance Tunneling through Subwavelength Hole Arrays in Highly Doped Conductive ZnO Films

Experimental results pertaining to plasmon resonance tunneling through a highly conductive zinc oxide (ZnO) layer with subwavelength hole-arrays is investigated in the mid-infrared regime. Gallium-doped ZnO layers are pulsed-laser deposited on a silicon wafer. The ZnO has metallic optical properties with a bulk plasma frequency of 214 THz, which is equivalent to a free space wavelength of 1.4 μm. Hole arrays with different periods and hole shapes are fabricated via a standard photolithography process. Resonant mode tunneling characteristics are experimentally studied for different incident angles and compared with surface plasmontheoretical calculations and finite-difference time-domain simulations. Transmission peaks, higher than the baseline predicted by diffraction theory, are observed in each of the samples at wavelengths that correspond to the excitation of surface plasmon modes

Comparative Genomics of Carriage and Disease Isolates of Streptococcus pneumoniae Serotype 22F Reveals Lineage-Specific Divergence and Niche Adaptation

Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom’s childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin-–antitoxin systems, were also observed

16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease

JJA is funded by a National Institute of Health Research Academic Clinical Fellowship and has received an Action Medical Research training fellowship. TC is funded by a Crohn’s in Childhood research association fellowship. CMC received a PhD studentship from SULSA Spirit industrial studentship. The NGS analysis was made possible by the award of a grant from the Source Bioscience 110th year anniversary promotion to CMC. The Rowett Institute receives funding from the Scottish Government (RESAS).Peer reviewedPublisher PD

Follow-up observations at 16 and 33 GHz of extragalactic sources from WMAP 3-year data: I - Spectral properties

We present follow-up observations of 97 point sources from the Wilkinson Microwave Anisotropy Probe (WMAP) 3-year data, contained within the New Extragalactic WMAP Point Source (NEWPS) catalogue between declinations of -4 and +60 degrees; the sources form a flux-density-limited sample complete to 1.1 Jy (approximately 5 sigma) at 33 GHz. Our observations were made at 16 GHz using the Arcminute Microkelvin Imager (AMI) and at 33 GHz with the Very Small Array (VSA). 94 of the sources have reliable, simultaneous -- typically a few minutes apart -- observations with both telescopes. The spectra between 13.9 and 33.75 GHz are very different from those of bright sources at low frequency: 44 per cent have rising spectra (alpha < 0.0), where flux density is proportional to frequency^-alpha, and 93 per cent have spectra with alpha < 0.5; the median spectral index is 0.04. For the brighter sources, the agreement between VSA and WMAP 33-GHz flux densities averaged over sources is very good. However, for the fainter sources, the VSA tends to measure lower values for the flux densities than WMAP. We suggest that the main cause of this effect is Eddington bias arising from variability.Comment: 12 pages, 13 figures, submitted to MNRA

Respiratory carriage of hypervirulent Klebsiella pneumoniae by indigenous populations of Malaysia

Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern. As K. pneumoniae can also exist as a harmless commensal, the spread of resistance genotypes requires epidemiological vigilance. However there has been no significant study of carriage isolates from healthy individuals, particularly in Southeast Asia, and specially Malaysia. Here we describe the genomic analysis of respiratory isolates of K. pneumoniae obtained from Orang Ulu and Orang Asli communities in Malaysian Borneo and Peninsular Malaysia respectively. The majority of isolates were K. pneumoniae species complex (KpSC) 1 K. pneumoniae (n = 53, 89.8%). Four Klebsiella variicola subsp. variicola (KpSC3) and two Klebsiella quasipneumoniae subsp. similipneumoniae (KpSC4) were also found. It was discovered that 30.2% (n = 16) of the KpSC1 isolates were ST23, 11.3% (n = 6) were of ST65, 7.5% (n = 4) were ST13, and 13.2% (n = 7) were ST86. Only eight of the KpSC1 isolates encoded ESBL, but importantly not carbapenemase. Thirteen of the KpSC1 isolates carried yersiniabactin, colibactin and aerobactin, all of which harboured the rmpADC locus and are therefore characterised as hypervirulent. Co-carriage of multiple strains was minimal. In conclusion, most isolates were KpSC1, ST23, one of the most common sequence types and previously found in cases of K. pneumoniae infection. A proportion were hypervirulent (hvKp) however antibiotic resistance was low

Cosmological parameter estimation using Very Small Array data out to l=1500

We estimate cosmological parameters using data obtained by the Very Small Array (VSA) in its extended configuration, in conjunction with a variety of other CMB data and external priors. Within the flat $\Lambda$CDM model, we find that the inclusion of high resolution data from the VSA modifies the limits on the cosmological parameters as compared to those suggested by WMAP alone, while still remaining compatible with their estimates. We find that $\Omega_{\rm b}h^2=0.0234^{+0.0012}_{-0.0014}$, $\Omega_{\rm dm}h^2=0.111^{+0.014}_{-0.016}$, $h=0.73^{+0.09}_{-0.05}$, $n_{\rm S}=0.97^{+0.06}_{-0.03}$, $10^{10}A_{\rm S}=23^{+7}_{-3}$ and $\tau=0.14^{+0.14}_{-0.07}$ for WMAP and VSA when no external prior is included.On extending the model to include a running spectral index of density fluctuations, we find that the inclusion of VSA data leads to a negative running at a level of more than 95% confidence ($n_{\rm run}=-0.069\pm 0.032$), something which is not significantly changed by the inclusion of a stringent prior on the Hubble constant. Inclusion of prior information from the 2dF galaxy redshift survey reduces the significance of the result by constraining the value of $\Omega_{\rm m}$. We discuss the veracity of this result in the context of various systematic effects and also a broken spectral index model. We also constrain the fraction of neutrinos and find that $f_{\nu}< 0.087$ at 95% confidence which corresponds to $m_\nu<0.32{\rm eV}$ when all neutrino masses are the equal. Finally, we consider the global best fit within a general cosmological model with 12 parameters and find consistency with other analyses available in the literature. The evidence for $n_{\rm run}<0$ is only marginal within this model