COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Características clínicas, pronóstico y factores asociados de la bacteriemia por Staphylococcus aureus en la actualidad / Clinical characteristics and prognosis of Staphylococcus aureus bacteremia

Introducción. Describimos las características de los pacientes con bacteriemia por Staphylococcus aureus en un hospital de tercer nivel y analizamos sus complicaciones, la mortalidad y los factores asociados a las mismas. Métodos. Se analizaron de manera retrospectiva los datos de los pacientes ingresados con bacteriemia por S. aureus entre marzo de 2020 y febrero de 2021 en el hospital universitario Miguel Servet de Zaragoza. Resultados. La mortalidad a los 14 días fue del 24,2% y la mortalidad a los 30 días del 40%. La aparición de complicaciones [HR 3,1 (1,2-8,05)] y la edad >65 años [HR 3,1 (IC95% 1,4-6,6)] disminuyeron la supervivencia global de manera significativa. En la regresión logística se asociaron a mayor mortalidad a los 30 días la edad >65 años [OR 6,3 (IC95% 1,7-23,1)], la presencia de sepsis [OR 19,3 (IC95% 5,4-68,7)] y solo con cierta tendencia, el número de frascos de HC (+) ≥3 [OR 5,4 (IC95% 0,8-34,1)]. Se asoció a mayor mortalidad a los 14 días el haber presentado sepsis [OR 58,2 (IC95% 5,7-592,9)], el número frascos de HC (+) ≥3 [OR 14,1 (IC95% 1,1-173,7)] y una edad >65 años [OR 1,1 (IC95% 1,03-1,1) años]. Cuando analizamos juntos aquellos con un TP ≤12 horas y un número frascos de HC (+) ≥3, la sepsis fue más frecuente [30 pacientes (66,6%) vs 15 pacientes (33,3%); OR 3,4 (IC95% 1,5-8)]. Conclusiones. La mortalidad a los 14 y a los 30 días fue elevada, observándose una peor evolución en los pacientes con mayor edad, presencia de sepsis, un mayor número de frascos de hemocultivos positivos y un tiempo hasta hemocultivos positivos ≤12 h. (AU)

Introduction. Staphylococcus aureus bacteremia patients characteristics at a tertiary hospital are described, and complications, mortality and associated factors are analyzed. Methods. Data from patients with S. aureus bacteremia admitted between March 2020 and February2021 at Miguel Servet university hospital in Zaragoza were retrospectively analyzed. Results. Results showed a 14 days mortality of 24.2% and an 30 days mortality of 40%. Overall survival decreased with complications appearance [HR 3.1 (1.2-8.05)] and age over 65 years [HR 3.1 (1.4-6.6)]. The adjusted analysis showed correlation between a higher mortality at 14 and 30 days with age over 65 years [OR 6.3 (1.7-23.1)], sepsis presence [OR 19.3 (5.4-68.7)] and number of positive (+) blood cultures ≥3 [OR 5.4 (0.8-34.1)]. Mortality at 14 days was associated with sepsis presence [OR 58.2 (5.7-592.9)], number of positive (+) blood cultures ≥3 [OR 14.1 (1.1-173.7)] and an older age [OR 1.1 (1.03-1.1)]. Analyzing time to positive blood cultures ≤12 hours and number of positive blood cultures ≥ 3 at the same time, frequency of sepsis increased [30 patients (66.6%) vs 15 patients (33.3%); OR 3.4 (IC95% 1.5-8)]. Conclusions. High 14- and 30-days mortality were found, as well as a worse evolution in older age patients, with sepsis presence, and with greater number of positive blood cultures and times to positive blood cultures ≤12 h. (AU)

Survival of Patient With Hemorrhagic Meningitis Associated With Inhalation Anthrax.

This report describes a 49-year-old male construction worker who acquired a Bacillus anthracis infection after working on a sheep farm. He experienced a severe respiratory infection, septic shock, and hemorrhagic meningoencephalitis with severe intracranial hypertension. After several weeks with multiple organ dysfunction syndrome, he responded favorably to antibiotic treatment. Three weeks into his hospitalization, an intracranial hemorrhage and cerebral edema led to an abrupt deterioration in his neurological status. A single dose of raxibacumab was added to his antimicrobial regimen on hospital day 27. His overall status, both clinical and radiographic, improved within a few days. He was discharged 2 months after admission and appears to have fully recovered.

Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19 / Impact of Staphylococcus aureus bacteremia in COVID-19 patients

Introducción. La enfermedad causada por SARS-CoV-2 (COVID-19) ha supuesto un desafío para los profesionales sanitarios desde su aparición. Staphylococcus aureus es uno de los principales patógenos causantes de infecciones bacterianas en pandemias virales. Sin embargo, se debe estudiar bien la co-infección por S. aureus causante de bacteriemia en pacientes con COVID-19. Métodos. Se analizaron los casos de bacteriemia por S. aureus (BSA) atendidos en el Hospital Miguel Servet (Zaragoza) desde marzo de 2020 hasta febrero de 2021. Se compararon las características clínicas, los factores de riesgo y mortalidad de los pacientes con BSA asociada a COVID-19 respecto los pacientes no-COVID-19. Resultados. Se identificaron 95 pacientes con BSA. El 27,3% fueron COVID-19 positivos. La BSA representó el 9,9% de las bacteriemias, siendo el segundo microorganismo en frecuencia tras E. coli. La bacteriemia nosocomial fue más frecuente en el grupo de pacientes con COVID-19. La fuente de BSA fue desconocida en el 46,2% de los pacientes con COVID-19. La fuente de BSA más frecuente en estos pacientes fue la respiratoria (26,9% vs 0%; P<0,001) seguida de la cutánea (15,5% vs 15,9%; P=1). El desarrollo de sepsis fue más frecuente en los pacientes con COVID-19 (61,5% vs 7,8%; P=0,336) y de ellos, los que recibieron dosis de dexametasona >6 mg/día (62,5% vs 37,5%; P< 0,05). Conclusiones. Nuestros datos sugieren que la BSA influye negativamente en la evolución de los pacientes con COVID-19. Sin embargo, se requieren más estudios y preferiblemente prospectivos para obtener datos sólidos sobre el impacto de la BSA en los pacientes con coronavirus. (AU)

Introduction. The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. Methods. We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. Results. A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). Conclusions. Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients. (AU)

Pacemaker-induced endocarditis by Gordonia bronchialis.

PURPOSE: Gordonia species are known to be opportunistic human pathogens causing secondary infections. We present the second case in the world of endocarditis caused by Gordonia bronchialis and a review of all the cases of endocarditis caused by Gordonia spp. METHODS: The identification was performed by matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were performed to confirm the identification. Antimicrobial susceptibility was performed by MIC test Strip on Mueller-Hinton agar supplemented with 5% defibrinated sheep blood according to Clinical and Laboratory Standards Institute. RESULTS: Pacemaker-induced endocarditis due to Gordonia bronchialis infection was determined in an 88-year old woman. The patient was treated with ceftriaxone and ciprofloxacin until completing 6 weeks from the pacemaker explant with a good evolution. CONCLUSION: The case presented supports the pathogenic role of Gordonia bronchialis as an opportunistic pathogen and highlights the high risk of suffering infections caused by environmental bacteria.

Pacemaker-induced endocarditis by Gordonia bronchialis / Endocarditis del marcapasos debido a infección por Gordonia bronchialis

PurposeGordonia species are known to be opportunistic human pathogens causing secondary infections. We present the second case in the world of endocarditis caused by Gordonia bronchialis and a review of all the cases of endocarditis caused by Gordonia spp.MethodsThe identification was performed by matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were performed to confirm the identification. Antimicrobial susceptibility was performed by MIC test Strip on Mueller-Hinton agar supplemented with 5% defibrinated sheep blood according to Clinical and Laboratory Standards Institute.ResultsPacemaker-induced endocarditis due to Gordonia bronchialis infection was determined in an 88-year old woman. The patient was treated with ceftriaxone and ciprofloxacin until completing 6 weeks from the pacemaker explant with a good evolution.ConclusionThe case presented supports the pathogenic role of Gordonia bronchialis as an opportunistic pathogen and highlights the high risk of suffering infections caused by environmental bacteria.

ObjetivoLas especies de Gordonia son patógenos humanos oportunistas que causan infecciones secundarias. Presentamos el segundo caso en el mundo de endocarditis causada por Gordonia bronchialis, así como una revisión de todos los casos de endocarditis causados por Gordonia spp.MétodosLa identificación fue realizada mediante espectrometría de masas MALDI-TOF MS, y se confirmó mediante secuenciación del gen 16S rRNA. La susceptibilidad antimicrobiana se realizó mediante tiras reactivas MIC en agar Müller-Hinton suplementado con un 5% de sangre ovina desfibrinada, conforme al Clinical and Laboratory Standards Institute (CLSI).ResultadosLa endocarditis del marcapasos debido a infección por Gordonia bronchialis se encontró en una mujer de 88 años. La paciente fue tratada con ceftriaxona y ciprofloxacina hasta completar el periodo de 6 semanas desde el explante del marcapasos, con buena evolución.ConclusiónEste caso respalda el rol patogénico de Gordonia bronchialis como patógeno oportunista, subrayando el alto riesgo de padecer infecciones causadas por bacterias ambientales.

Bacteremia during COVID-19 pandemic in a tertiary hospital in Spain.

INTRODUCTION: The reasons for the decrease in blood cultures were investigated and the rate and aetiology of bacteremia and contaminated blood cultures collected from COVID and non-COVID patients were assessed. METHODS: We performed a retrospective analysis in a tertiary hospital in Spain during the COVID period from 4th March 2020 to 21st June 2020. RESULTS: The number of blood cultures processed was 5313, representing 22.7% and 18.8% of decrease compared to the same months of 2019 and 2018, respectively (p=0.173). The rate of bacteremia was 1.2% higher among COVID-patients than among non-COVID patients (p<0.001). COVID patients had a higher proportion of nosocomial bacteremia (95.5%) than non-COVID patients (30.5%) (p<0.001). In COVID-positive patients, the contamination rate was 12.3% vs 5.7% in non-COVID patients (p<0.001). CONCLUSION: There was a decrease in the number of blood cultures collected during the COVID period compared to previous years. Bacteremia in COVID patients was mainly nosocomial and catheter-related.

Bacteremia during COVID-19 pandemic in a tertiary hospital in Spain / Bacteriemia durante la pandemia de COVID-19 en un hospital terciario de España

IntroductionThe reasons for the decrease in blood cultures were investigated and the rate and aetiology of bacteremia and contaminated blood cultures collected from COVID and non-COVID patients were assessed.MethodsWe performed a retrospective analysis in a tertiary hospital in Spain during the COVID period from 4th March 2020 to 21st June 2020.ResultsThe number of blood cultures processed was 5313, representing 22.7% and 18.8% of decrease compared to the same months of 2019 and 2018, respectively (p=0.173). The rate of bacteremia was 1.2% higher among COVID-patients than among non-COVID patients (p<0.001). COVID patients had a higher proportion of nosocomial bacteremia (95.5%) than non-COVID patients (30.5%) (p<0.001). In COVID-positive patients, the contamination rate was 12.3% vs 5.7% in non-COVID patients (p<0.001).ConclusionThere was a decrease in the number of blood cultures collected during the COVID period compared to previous years. Bacteremia in COVID patients was mainly nosocomial and catheter-related.

IntroducciónInvestigar la causa de la disminución de los hemocultivos recibidos y evaluar la tasa y la etiología de la bacteriemia y la contaminación de los hemocultivos extraídos en pacientes con COVID-19 y sin COVID-19.MétodosEstudio retrospectivo en un hospital de tercer nivel en España durante el periodo de COVID-19 del 4 de marzo al 21 de junio de 2020.ResultadosSe procesaron 5.313 hemocultivos, representando una disminución del 22,7 y 18,8% respecto de los mismos meses de 2019 y 2018 (p = 0,173). La tasa de bacteriemia fue 1,2% superior en pacientes con COVID-19 (p < 0,001). Los pacientes positivos en COVID-19 tenían una mayor proporción de bacteriemia nosocomial (95,5%) que los pacientes sin COVID-19 (30,5%) (p < 0,001). En pacientes positivos en COVID-19, la tasa de contaminación fue del 12,3 vs. 5,7% en pacientes sin COVID-19 (p < 0,001).ConclusiónDurante el periodo de COVID-19 disminuyó el número de hemocultivos recibidos, en comparación con años anteriores. La bacteriemia en pacientes con COVID-19 fue principalmente nosocomial y se asoció con el catéter.

Impacto del SARS-CoV-2 en el diagnóstico de bacteriemia comunitaria en un hospital terciario / Impact of SARS-COV-2 on the diagnosis of community bacteremia in a tertiary hospital

Objetivo. Realizar un análisis de las bacteriemias diagnosticadas en urgencias durante el año 2020, coincidiendo con el periodo de la pandemia Métodos. Estudio retrospectivo en un hospital de tercer nivel en España durante el período COVID del 4 de marzo al 31 de diciembre de 2020. Resultados. El número de pacientes atendidos en urgencias durante el periodo de estudio y el número de hemocultivos extraídos sufrieron un descenso del 46,79% y del 35.7% respecto al mismo periodo de 2019 (p<0.05). Se produjeron 320 bacteriemias mientas que en 2019 se produjeron 507, suponiendo un descenso del 36,8% (p<0,05). La tasa de positividad de los hemocultivos fue del 7,09 % en 2020 y del 7,23 % en 2019 y la tasa de contaminación del 7,07 % en 2020 y 5,67 % en 2019. El microorganismo más frecuente aislado fue Escherichia coli, seguido de Staphylococcus aureus y de Klebsiella pneumoniae. El 6,62% de los E. coli aislados fueron portadores de beta-lactamasas de espectro extendido (BLEE). El porcentaje de S. aureus resistente a meticilina fue de 12,9 % y el de K. pneumoniae BLEE fue del 11,54 %. Conclusión. Durante la pandemia por SARS-CoV-2 se ha producido una disminución en el número de diagnósticos de bacteriemia, es posible que la atención estuviera centrada especialmente en la COVID descuidando otras enfermedades, como es el caso de la bacteriemia. (AU)

Objective. We carry out an analysis of the bacteremia diagnosed in the Emergency Department during 2020, coinciding with the period of the pandemic. Method. We performed a retrospective analysis from March 4, 2020 to December 31, 2020. Results. The number of patients who went to the Emergency Department during the study period and the number of extracted blood cultures decreased by 46.79% and 35.7% compared to the same period in 2019 (p <0.05). 320 bacteremia occurred while 507 occurred in 2019, assuming a decrease of 36.8% (p <0.05). The positivity rate of blood cultures was 7.09% in 2020 and 7.23% in 2019 and the contamination rate was 7.07 % in 2020 and 5.67% in 2019. The most frequently isolated microorganism was Escherichia coli, followed by Staphylococcus aureus and Klebsiella pneumoniae. A 6.62% of the isolated E. coli were carriers of extended-spectrum beta-lactamases (ESBL). The percentage of methicillin-resistant S. aureus was 12.9 % and that of K. pneumoniae ESBL was 11.54%. Conclusion. During the SARS-CoV-2 pandemic there has been a decrease in the number of bacteremia diagnoses, it is possible that attention was focused especially on COVID, forgetting other diseases, such as bacteremia. (AU)

Bacteremia during COVID-19 pandemic in a tertiary hospital in Spain.

INTRODUCTION: The reasons for the decrease in blood cultures were investigated and the rate and aetiology of bacteremia and contaminated blood cultures collected from COVID and non-COVID patients were assessed. METHODS: We performed a retrospective analysis in a tertiary hospital in Spain during the COVID period from 4th March 2020 to 21st June 2020. RESULTS: The number of blood cultures processed was 5313, representing 22.7% and 18.8% of decrease compared to the same months of 2019 and 2018, respectively (p=0.173). The rate of bacteremia was 1.2% higher among COVID-patients than among non-COVID patients (p<0.001). COVID patients had a higher proportion of nosocomial bacteremia (95.5%) than non-COVID patients (30.5%) (p<0.001). In COVID-positive patients, the contamination rate was 12.3% vs 5.7% in non-COVID patients (p<0.001). CONCLUSION: There was a decrease in the number of blood cultures collected during the COVID period compared to previous years. Bacteremia in COVID patients was mainly nosocomial and catheter-related.

Pacemaker-induced endocarditis by Gordonia bronchialis.

PURPOSE: Gordonia species are known to be opportunistic human pathogens causing secondary infections. We present the second case in the world of endocarditis caused by Gordonia bronchialis and a review of all the cases of endocarditis caused by Gordonia spp. METHODS: The identification was performed by matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were performed to confirm the identification. Antimicrobial susceptibility was performed by MIC test Strip on Mueller-Hinton agar supplemented with 5% defibrinated sheep blood according to Clinical and Laboratory Standards Institute. RESULTS: Pacemaker-induced endocarditis due to Gordonia bronchialis infection was determined in an 88-year old woman. The patient was treated with ceftriaxone and ciprofloxacin until completing 6 weeks from the pacemaker explant with a good evolution. CONCLUSION: The case presented supports the pathogenic role of Gordonia bronchialis as an opportunistic pathogen and highlights the high risk of suffering infections caused by environmental bacteria.

Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.

BACKGROUND: Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. METHODS: In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. RESULTS: Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60-79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17-10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). CONCLUSIONS: In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Application of a new method for the detection of catheter colonization and catheter-related bacteraemia in newborns / Aplicación de un nuevo método para la detección de colonización y bacteriemia relacionada con catéter en neonatos

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Crystal structure and mutational analysis of Mycobacterium smegmatis FenA highlight active site amino acids and three metal ions essential for flap endonuclease and 5' exonuclease activities.

Mycobacterium smegmatis FenA is a nucleic acid phosphodiesterase with flap endonuclease and 5' exonuclease activities. The 1.8 Å crystal structure of FenA reported here highlights as its closest homologs bacterial FEN-family enzymes ExoIX, the Pol1 exonuclease domain and phage T5 Fen. Mycobacterial FenA assimilates three active site manganese ions (M1, M2, M3) that are coordinated, directly and via waters, to a constellation of eight carboxylate side chains. We find via mutagenesis that the carboxylate contacts to all three manganese ions are essential for FenA's activities. Structures of nuclease-dead FenA mutants D125N, D148N and D208N reveal how they fail to bind one of the three active site Mn2+ ions, in a distinctive fashion for each Asn change. The structure of FenA D208N with a phosphate anion engaged by M1 and M2 in a state mimetic of a product complex suggests a mechanism for metal-catalyzed phosphodiester hydrolysis similar to that proposed for human Exo1. A distinctive feature of FenA is that it does not have the helical arch module found in many other FEN/FEN-like enzymes. Instead, this segment of FenA adopts a unique structure comprising a short 310 helix and surface ß-loop that coordinates a fourth manganese ion (M4).

The DNA Repair Repertoire of Mycobacterium smegmatis FenA Includes the Incision of DNA 5' Flaps and the Removal of 5' Adenylylated Products of Aborted Nick Ligation.

We characterize Mycobacterium smegmatis FenA as a manganese-dependent 5'-flap endonuclease homologous to the 5'-exonuclease of DNA polymerase I. FenA incises a nicked 5' flap between the first and second nucleotides of the duplex segment to yield a 1-nucleotide gapped DNA, which is then further resected in dinucleotide steps. Initial FenA cleavage at a Y-flap or nick occurs between the first and second nucleotides of the duplex. However, when the template 3' single strand is eliminated to create a 5'-tailed duplex, FenA incision shifts to between the second and third nucleotides. A double-flap substrate with a mobile junction (mimicking limited strand displacement synthesis during gap repair) is preferentially incised as the 1-nucleotide 3'-flap isomer, with the scissile phosphodiester shifted by one nucleotide versus a static double flap. FenA efficiently removes the 5' App(dN) terminus of an aborted nick ligation reaction intermediate, thereby highlighting FenA as an agent of repair of such lesions, which are formed under a variety of circumstances by bacterial NAD+-dependent DNA ligases and especially by mycobacterial DNA ligases D and C.IMPORTANCE Structure-specific DNA endonucleases are implicated in bacterial DNA replication, repair, and recombination, yet there is scant knowledge of the roster and catalytic repertoire of such nucleases in Mycobacteria This study identifies M. smegmatis FenA as a stand-alone endonuclease homologous to the 5'-exonuclease domain of mycobacterial DNA polymerase 1. FenA incises 5' flaps, 5' nicks, and 5' App(dN) intermediates of aborted nick ligation. The isolated N-terminal domain of M. smegmatis Pol1 is also shown to be a flap endonuclease.

Epidemiological investigation of the first human brucellosis case in Spain due to Brucella suis biovar 1 strain 1330 / Investigación epidemiológica del primer caso de brucelosis humana en España por Brucella suis biovariedad 1 cepa 1330

INTRODUCTION: No cases of human brucellosis caused by Brucella suis has been reported in Spain. METHODS: This study involved interviews with the case and his co-workers, inspection of their workplace, checking infection control measures, and typing the Brucella strain isolated in the blood culture. RESULTS: Brucella suis biovar 1 strain 1330 was isolated from a patient who worked in a waste treatment plant. Food borne transmission, contact with animals, and risk jobs were ruled out. An accidental inoculation with a contaminated needle from a research laboratory waste container was identified as the most probable mode of transmission. CONCLUSION: There should be controls to ensure that waste containers are sealed

INTRODUCCIÓN: En España no se habían comunicado casos humanos de brucelosis por Brucella suis anteriores a este. MÉTODOS: La investigación incluyó entrevistas con el caso y sus compañeros de trabajo, inspección del lugar de trabajo, comprobación de las medidas de control de la infección, y tipificación de la cepa de Brucella aislada en el hemocultivo. RESULTADOS: Se aisló Brucella suis biovariedad 1 cepa 1330 en un paciente que trabajaba en una empresa de tratamiento de residuos. Se descartó la fuente alimentaria, el contacto con animales y trabajos de riesgo. Un pinchazo accidental con una aguja contaminada de un contenedor procedente de un laboratorio de investigación fue la forma de transmisión más probable. CONCLUSIÓN: Se deben realizar controles para asegurar que los contenedores de residuos están sellados

Epidemiological investigation of the first human brucellosis case in Spain due to Brucella suis biovar 1 strain 1330.

INTRODUCTION: No cases of human brucellosis caused by Brucella suis has been reported in Spain. METHODS: This study involved interviews with the case and his co-workers, inspection of their workplace, checking infection control measures, and typing the Brucella strain isolated in the blood culture. RESULTS: Brucella suis biovar 1 strain 1330 was isolated from a patient who worked in a waste treatment plant. Food borne transmission, contact with animals, and risk jobs were ruled out. An accidental inoculation with a contaminated needle from a research laboratory waste container was identified as the most probable mode of transmission. CONCLUSION: There should be controls to ensure that waste containers are sealed.

Mycobacterium smegmatis HelY Is an RNA-Activated ATPase/dATPase and 3'-to-5' Helicase That Unwinds 3'-Tailed RNA Duplexes and RNA:DNA Hybrids.

UNLABELLED: Mycobacteria have a large and distinctive ensemble of DNA helicases that function in DNA replication, repair, and recombination. Little is known about the roster of RNA helicases in mycobacteria or their roles in RNA transactions. The 912-amino-acid Mycobacterium smegmatis HelY (MSMEG_3885) protein is a bacterial homolog of the Mtr4 and Ski2 helicases that regulate RNA 3' processing and turnover by the eukaryal exosome. Here we characterize HelY as an RNA-stimulated ATPase/dATPase and an ATP/dATP-dependent 3'-to-5' helicase. HelY requires a 3' single-strand RNA tail (a loading RNA strand) to displace the complementary strand of a tailed RNA:RNA or RNA:DNA duplex. The findings that HelY ATPase is unresponsive to a DNA polynucleotide cofactor and that HelY is unable to unwind a 3'-tailed duplex in which the loading strand is DNA distinguish HelY from other mycobacterial nucleoside triphosphatases/helicases characterized previously. The biochemical properties of HelY, which resemble those of Mtr4/Ski2, hint at a role for HelY in mycobacterial RNA catabolism. IMPORTANCE: RNA helicases play crucial roles in transcription, RNA processing, and translation by virtue of their ability to alter RNA secondary structure or remodel RNA-protein interactions. In eukarya, the RNA helicases Mtr4 and Ski2 regulate RNA 3' resection by the exosome. Mycobacterium smegmatis HelY, a bacterial homolog of Mtr4/Ski2, is characterized here as a unidirectional helicase, powered by RNA-dependent ATP/dATP hydrolysis, that tracks 3' to 5' along a loading RNA strand to displace the complementary strand of a tailed RNA:RNA or RNA:DNA duplex. The biochemical properties of HelY suggest a role in bacterial RNA transactions. HelY homologs are present in pathogenic mycobacteria (e.g., M. tuberculosis and M. leprae) and are widely prevalent in Actinobacteria and Cyanobacteria but occur sporadically elsewhere in the bacterial domain.

Distinctive Structure of the EphA3/Ephrin-A5 Complex Reveals a Dual Mode of Eph Receptor Interaction for Ephrin-A5.

The Eph receptor tyrosine kinase/ephrin ligand system regulates a wide spectrum of physiological processes, while its dysregulation has been implicated in cancer progression. The human EphA3 receptor is widely upregulated in the tumor microenvironment and is highly expressed in some types of cancer cells. Furthermore, EphA3 is among the most highly mutated genes in lung cancer and it is also frequently mutated in other cancers. We report the structure of the ligand-binding domain of the EphA3 receptor in complex with its preferred ligand, ephrin-A5. The structure of the complex reveals a pronounced tilt of the ephrin-A5 ligand compared to its orientation when bound to the EphA2 and EphB2 receptors and similar to its orientation when bound to EphA4. This tilt brings an additional area of ephrin-A5 into contact with regions of EphA3 outside the ephrin-binding pocket thereby enlarging the size of the interface, which is consistent with the high binding affinity of ephrin-A5 for EphA3. This large variation in the tilt of ephrin-A5 bound to different Eph receptors has not been previously observed for other ephrins.