Proposing Kluyvera georgiana as the Origin of the Plasmid-Mediated Resistance Gene fosA4

A putative fosA gene in Kluyvera georgiana 14751 showed 99% nucleotide identity with plasmid-encoded fosA4. Due to a single-nucleotide insertion translating to a truncated protein, K. georgiana 14751 fosA does not confer fosfomycin resistance. However, analysis of another genome deposit (Kluyvera ascorbata WCH1410) that could be recategorized as K. georgiana after phylogenetic analysis revealed a fosA gene 100% identical to the plasmid-borne fosA4 gene. We suggest that Kluyvera georgiana represents the most probable origin of fosA4.Fil: Rodriguez, Maria Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiglione, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Power, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Naas, Thierry. Hôpital de Bicêtre. Service de Bactériologie Hygiène; FranciaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Molecular and biochemical characterization of CTX-M-131, a natural Asp240Gly variant derived from CTX-M-2, produced by a Providencia rettgeri clinical strain in São Paulo, Brazil

CTX-M-131 is a natural Asp240Gly variant from the CTX-M-2 group detected in a Providencia rettgeri clinical strain from Brazil. Molecular analysis showed that blaCTX-M-131 was inserted in a complex class 1 integron harbored by a 112-kb plasmid, which has not been previously described as a platform for CTX-M-encoding genes with the Asp240Gly mutation. Steady-state kinetic parameters showed that the enzyme has a typical cefotaximase catalytic profile and an enhanced activity against ceftazidime.Fil: Dropa, Milena. Universidade de Sao Paulo; BrasilFil: Ghiglione, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Matté, Maria Helena. Universidade de Sao Paulo; BrasilFil: Balsalobre, Livia Carminato. Universidade de Sao Paulo; BrasilFil: Lincopan, Nilton. Universidade de Sao Paulo; BrasilFil: Matté, Glavur Rogério. Universidade de Sao Paulo; BrasilFil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Opportunities for and challenges of occupational pluralism in seasonal fisheries: Regional cases from Atlantic Canada

This report presents the findings from the Atlantic Canada case studies component of the Canadian Council of Professional Fish Harvesters’ (CCPFH) national study entitled Fisheries Seasonality and the Allocation of Labour and Skills Labour Market Information, which was funded by Human Resources and Skills Development Canada. The Atlantic Canada case studies were coordinated by the Newfoundland and Labrador (NL)-based Professional Fish Harvesters Certification Board and carried out by Memorial University researchers Dr. Paul Foley (School of Science and Environment, Grenfell Campus), Dr. Barbara Neis (Sociology) and Dr. Nicole Power (Sociology), with help from Research Assistants Christine Knott (PhD student, Sociology) and Dr. Courtenay Parlee. The funds were administered by Memorial University and the research was carried out with support from the On the Move Partnership (www.onthemovepartnership.ca)

"Bringing heaven down to earth”: The purpose and place of religion in UK food aid

yesThis paper uses data from a city with a multi-ethnic, multi-faith population to better understand faith-based food aid. It aims to understand what constitutes faith-based responses to food insecurity; compare the prevalence and nature of faith-based food aid across different religions; and explore how community food aid meets the needs of a multi-ethnic, multi-faith population. Methodology The study involved two phases of primary research. In phase one, desk-based research and dialogue with stakeholders in local food security programmes was used to identify faith- based responses to food insecurity. Phase two consisted of 18 semi-structured interviews involving faith-based and secular charitable food aid organizations. Findings The paper illustrates the internal heterogeneity of faith-based food aid. Faith-based food aid is highly prevalent and the vast majority is Christian. Doctrine is a key motivation among Christian organizations for their provision of food. The fact that the clients at faith-based, particularly Christian, food aid did not reflect the local religious demographic is a cause for concern in light of the entry-barriers identified. This concern is heightened by the co-option of faith-based organizations by the state as part of the ‘Big Society’ agenda. Originality This is the first academic study in the UK to look at the faith-based arrangements of Christian and Muslim food aid providers, to set out what it means to provide faith-based food aid in the UK and to explore how faith-based food aid interacts with people of other religions and no religion

Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam

The diazabicyclooctane (DBO) inhibitor avibactam (AVI) reversibly inactivates most serine β-lactamases, including the CTX-M β-lactamases. Currently, more than 230 unique CTX-M members distributed in five clusters with less than 5% amino acid sequence divergence within each group have been described. Recently, a variant named CTX-M-151 was isolated from a Salmonella enterica subsp. enterica serovar Choleraesuis strain in Japan. This variant possesses a low degree of amino acid identity with the other CTX-Ms (63.2% to 69.7% with respect to the mature proteins), and thus it may represent a new subgroup within the family. CTX-M-151 hydrolyzes ceftriaxone better than ceftazidime (kcat/Km values 6,000-fold higher), as observed with CTX-Ms. CTX-M-151 is well inhibited by mechanism-based inhibitors like clavulanic acid (inactivation rate [kinact]/inhibition constant [Ki] = 0.15μM-1 · s-1). For AVI, the apparent inhibition constant (Ki app), 0.4mM, was comparable to that of KPC-2; the acylation rate (k2/K) (37,000 M-1 · s-1) was lower than that for CTX-M-15, while the deacylation rate (koff) (0.0015 s21) was 2- to 14-fold higher than those of other class A β-lactamases. The structure of the CTX-M-151/AVI complex (1.32 Å) reveals that AVI adopts a chair conformation with hydrogen bonds between the AVI carbamate and Ser70 and Ser237 at the oxyanion hole. Upon acylation, the side chain of Lys73 points toward Ser130, which is associated with the protonation of Glu166, supporting the role of Lys73 in the proton relay pathway and Glu166 as the general base in deacylation. To our knowledge, this is the first chromosomally encoded CTX-M in Salmonella Choleraesuis that shows similar hydrolytic preference toward cefotaxime (CTX) and ceftriaxone (CRO) to that toward ceftazidime (CAZ).Fil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Rodríguez, María Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Brunetti, Florencia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados UnidosFil: Yoshizumi, Ayumi. Toho University; JapónFil: Ishii, Yoshikazu. Toho University; JapónFil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentin

SAMI-HI: the connection between global asymmetry in the ionised and neutral atomic hydrogen gas in galaxies

Observations of the neutral atomic hydrogen (HI) gas in galaxies are predominantly spatially unresolved, in the form of a global HI spectral line. There has been substantial work on quantifying asymmetry in global HI spectra (`global HI asymmetry'), but due to being spatially unresolved, it remains unknown what physical regions of galaxies the asymmetry traces, and whether the other gas phases are affected. Using optical integral field spectrograph (IFS) observations from the Sydney AAO Multi-object IFS (SAMI) survey for which global HI spectra are also available (SAMI-HI), we study the connection between asymmetry in galaxies' ionised and neutral gas reservoirs to test if and how they can help us better understand the origin of global HI asymmetry. We reconstruct the global H$\alpha$ spectral line from the IFS observations and find that, while some global H$\alpha$ asymmetries can arise from disturbed ionised gas kinematics, the majority of asymmetric cases are driven by the distribution of H$\alpha$-emitting gas. When compared to the HI, we find no evidence for a relationship between the global H$\alpha$ and HI asymmetry. Further, a visual inspection reveals that cases where galaxies have qualitatively similar H$\alpha$ and HI spectral profiles can be spurious, with the similarity originating from an irregular 2D H$\alpha$ flux distribution. Our results highlight that comparisons between global H$\alpha$ and HI asymmetry are not straightforward, and that many global HI asymmetries trace disturbances that do not significantly impact the central regions of galaxies.Comment: 11 pages, 6 figures, 1 appendix, accepted for publication in MNRA

Comparative Kinetic Analysis of OXA-438 with Related OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamases

Novel variants of OXA-48-type enzymes with the ability to hydrolyze oxyimino-cephalosporins and carbapenems are increasingly reported. Since its first report in 2011, OXA-163 is now extensively spread throughout Argentina, and several variants like OXA-247 have emerged. Here, we characterized a new blaOXA-48-like variant, OXA-438, and we performed a comparative kinetic analysis with the local variants OXA-247 and OXA-163 and the internationally disseminated OXA-48. blaOXA-163, blaOXA-247, and blaOXA-438 were located in a 70 kb IncN2 conjugative plasmid. OXA-438 presented mutations in the vicinity of conserved KTG (214-216), with a 2-aa deletion (R220-I221) and a D224E shift (as in OXA-163) compared to OXA-48. Despite Kpn163 (OXA-163), Kpn247 (OXA-247) and Eco438 (OXA-438) were resistant to meropenem and ertapenem, and the transconjugants (TC) remained susceptible (however, the carbapenems minimum inhibitory concentrations were ≥3 times 2-fold dilutions higher than the acceptor strain). TC163 and Eco48 were resistant to oxyimino-cephalosporins, unlike TC247 and TC438. kcat/Km values for cefotaxime in OXA-163 were slightly higher than the rest of the variants that were accompanied by a lower Km for carbapenems. For OXA-163, OXA-247, and OXA-438, the addition of NaHCO3 improved kcat values for both cefotaxime and ceftazidime; carbapenems kcat/Km values were higher than for oxyimino-cephalosporins. Mutations occurring near the conserved KTG in OXA-247 and OXA-438 are probably responsible for the improved carbapenems hydrolysis and decreased inactivation of oxyimino-cephalosporins compared to OXA-163. Dichroism results suggest that deletions at the β5-β6 loop seem to impact the structural stability of OXA-48 variants. Finally, additional mechanisms are probably involved in the resistance pattern observed in the clinical isolates.Fil: de Belder, Denise Gisele. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ghiglione, Barbara. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Pasteran, Fernando. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; ArgentinaFil: de Mendieta, Juan Manuel. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; ArgentinaFil: Corso, Alejandra. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; ArgentinaFil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Di Bella, Adriana. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Gutkind, Gabriel Osvaldo. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Gómez, Sonia Alejandra. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires

Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.

Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth