The virulence of Streptococcus pneumoniae partially depends on dprA

Abstract Streptococcus pneumoniae is one of the most frequent opportunistic pathogens worldwide. DNA processing protein A (DprA) is an important factor involved in bacterial uptake and DNA integration into bacterial genome, but its role in S. pneumoniae virulence remains unclear. The aim of this study was to characterize the effects of the pneumococcal dprA gene on the pathogenesis of S. pneumoniae. To construct a dprA-deficient pneumococcal strain, the dprA gene of the S. pneumoniae strain D39 was inactivated. The virulence of this dprA-deficient strain, designated ΔD39, was compared with that of the wild-type strain by evaluating their respective capabilities to adhere to human pulmonary epithelial cells (PEC-A549) and by analyzing their choline-binding protein expression levels. In addition, the expression profiles of genes associated with virulence and host survival assays were also conducted with the mutant and the wild-type strain. Our results indicate that the capability of ΔD39 to adhere to the PEC-A549 airway cells was significantly lower (p < 0.01) compared with D39. Additionally, the 100-KD choline-binding protein was not detected in ΔD39. The addition of competence-stimulating peptide (CSP) lead to a significantly reduction of psaA mRNA expression in the dprA-deficient mutant and an increased level of psaA transcripts in the wild-type strain (p < 0.01). The median survival time of mice intraperitoneally infected with ΔD39 was significantly higher (p < 0.01) than that of mice infected with D39. The results of this study suggest that DprA has a significant effect on virulence characteristics of S. pneumoniae by influencing the expression of choline-binding protein and PsaA.

Asplenia congénita y purpura fulminans neumocóccico en paciente pediátrico: reporte de caso con necropsia y revisión del tema / Congenital asplenia and pneumococcal purpura fulminans in a pediatric patient: case report with pathological findings and review

Absent or defective splenic function is associated with a high risk of fulminant bacterial infections, especially due to encapsulated bacteria. Not knowing this condition may delay medical treatment. Streptococcus pneumoniae is the leading cause of sepsis in these patients. Asplenic patients are at high risk for septic shock and eventually purpura fulminans, a life-threatening condition. We report the case of a 3 years oíd girl, with mitral stenosis and recurrent pneumonía that was admitted due to fever but in the next few hours presented hypotension, purpura and livedo reticularis. Laboratory test showed leucopenia (3.400/mm³), bandemia (43 percent of immature forms), thrombocytopenia, hypoprothombinemia and severe lactic acidosis (ph: 7.0 and lactic acid 11 mmol/1). The patient developed septic shock and multiorganic failure. Mechanical ventilation, volume resuscitation, vasoactive drugs and antibiotic therapy was initiated. Ultrasound was performed on the second day, demostrating asplenia. Peripheral blood smear showed Howell-Jolly bodies. Patient had a positive blood culture for penicillin-resistant Streptococcus pneumoniae (serotype 19F). Patient died of intracerebral hemorrhage after 8 days of admission. Necropsy confirmed asplenia and bilateral suprarenal haemorrhage. Absence of spleen can lead to life threatening infections, it is important to recognize it because vaccination and antibiotic prophylaxis can provide life-saving protection. This case provides a reminder to pursue asplenia as a potential underlying mechanism for invasive bacterial infection in children.

La condición de asplenia predispone a infecciones invasoras por bacterias capsuladas. Desconocer previamente ese antecedente dificulta y retarda el tratamiento médico. Streptococcus pneumoniae es el agente habitualmente causal de sepsis en estos pacientes. Los individuos asplénicos son particularmente proclives a evolucionar con shock séptico y eventual-mente al desarrollo de purpura fulminans, entidad altamente letal. Comunicamos el caso de una paciente con 3 años de edad y antecedente de cardiopatía y neumonías a repetición. Ingresó con compromiso sensorial, febril, hipotensa, con púrpura y livedo reticularis. En los exámenes de laboratorio destacaba la presencia de leucopenia (3.400/ mm³) trombopenia e hipoprotrombinemia (39 por ciento). Se inició ventilación mecánica, reanimación con volumen, fármacos vasoactivos y antibioterapia con vancomicina, clindamicina y ceftriaxona. Evolucionó con shock séptico refractario y síndrome de disfunción orgánica múltiple. Al segundo día de evolución una ecograña de abdomen comprobó la ausencia de bazo. En el frotis sanguíneo se evidenciaron corpúsculos de Howell-Jolly. Hemocul-tivo (+) S. pneumoniae resistente a penicilina (serotipo 19F). Un infarto hemorrágico cerebral ocasionó su deceso al octavo día. El estudio necrópsico corroboró la asplenia y evidenció necrohemorragia suprarrenal bilateral. La sepsis en un paciente asplénico puede ser de alguna forma prevenible mediante profilaxis antimicrobiana y vacunación neumocóccica. Dado los antecedentes de la paciente la búsqueda de asplenia era fundamental.

Achados otomicroscópicos e histológicos da miringoesclerose induzida em ratos: estudo crítico de um modelo experimental / Otomicroscopic and histologic findings of induced myringosclerosis in rats: a critical study of an experimental model

A miringoesclerose é caracterizada por hialinização da lâmina própria da membrana timpânica. Trabalhos experimentais têm utilizado a otomicroscopia ou a histologia para estudar a miringoesclerose em animais, porém sem correlacionar precisamente estes dois métodos de avaliação. OBJETIVO: Este estudo procura avaliar a acurácia da otomicroscopia no diagnóstico de miringoesclerose em modelo experimental com ratos. FORMA DE ESTUDO: experimental. MATERIAL E MÉTODO: Foi induzida miringoesclerose por inoculação transtimpânica de Streptococcus pneumoniae em 25 ratos Wistar, que foram examinados quinzenalmente por otomicroscopia e sacrificados após oito semanas, tendo suas membranas timpânicas examinadas por histologia. RESULTADOS: Da confrontação das alterações otomicroscópicas com os achados histológicos, houve uma sensibilidade de 80 por cento e especificidade de 75 por cento. CONCLUSÃO: Pelos resultados obtidos neste estudo, a otomicroscopia não representou um bom método para avaliar a miringoesclerose neste modelo experimental.

Ultrastructural Characteristics of the Round Window Membrane During Pneumococcal Otitis Media in Rat

To understand better the pathogenesis of inner ear (IE) damage caused by otitis media (OM), the round window membrane(RWM) structure was investigated in a rat model for pneumococcal otitis media (POM). The RWM of 25 rats were evaluated light and electron microscopically on 1 day, 3 days, 6 days, 10 days, and 20 days after the unilateral inoculation of type 3 pneumococcus suspension into their middle ear cavities. The thickness of the RWM increased in various stages of the pneumococcus-evoked otitis media, compared with that of the normal. The thickening was most pronounced on day 1, being about 4 to 5 times greater than that of the normal RWM. All layers of the RWM were affected by the pneumococcal infection, but the major changes were confined to the subepithelial space close to the basement membrane (BM). Together with alterations to the BM, the most distinct pathological features were characterized by an increase and hypertrophy of fibroblasts in association with abundant collagen fibers. Elastic fibers observed close to the inner mesothelial layer under a high power magnification also increased during the experiment. These results will be relevant to a better understanding of the histologic implication of RWM in stages of acute otitis media involving pneumococcus-evoked otitis media.

Estudio clínico epidemiológico de las neumonías en un hospital del Estado Carabobo, Venezuela, 1989-1993 / Study clinical epidemiology of the pneumonia in hospital the state Carabobo, Venezuela 1989-1993

Se presenta un estudio descriptivo de 129 pacientes cuyo diagnóstico de egreso fue neumonía epidémica infecciosa, seleccionado mediante la revisión de 147 historias clínicas de pacientes hospitalizados entre 1989 y 1993. Los resultados revelan una mayor incidencia (44,19 por ciento) durante enero, julio y agosto, con un promedio de estancia hospitalaria menor de 14 días en el 77,22 por ciento de los pacientes. El grupo de edad más afectado fue entre 21 y 47 años, y las complicaciones más frecuentes el abscenso pulmonar y el derrame pleural. El 50,63 por ciento de los pacientes entre 21 y 38 años presentan antecedentes de consumo combinado de sustancias lícitas e ilícitas, y el 69,23 por ciento de los menores de 21 años consume drogas ilícitas. Se identificó el agente etiológico en 13 de 129 pacientes, y 108 de ellos no fueron muestreados. Streptococcus pneumoniae fue el agente aislado con mayor frecuencia, y la penicilina, como monoterapia, fue utilizada en el 62,01 por ciento. Se concluye que el consumo de drogas lícitas e ilícitas, la falta de recursos institucionales y la ausencia de identificación de los agentes causales influye en la patogenia de la enfermedad y en las posibilidades de éxito terapéutico

Neumonías: diagnóstico-evaluación y tratamiento en el Hospimil San Cristobal: enero 1993-junio 1995 / Pneumonia: diagnosis-evaluation and treatment in the Hospimil San Cristobal: january 1993-june 1995

Las infecciones del tracto respitarorio son aún una causa importante de morbilidad y mortalidad; la selección de un tratamiento antibiótico específico de la neumonía, depende de la identificación del patógeno causante o del juicio sobre el mismo. En este estudio retrospectivo se analizaron 80 pacientes hospitalizados en el Hospimil San Cristobal, su evolución y seguimiento intrahospitalario. Para definir criterios y conductas a seguir en el manejo más adecuado con neumonías en nuestro Hospimil