RESUMEN
Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Proteínas Portadoras/metabolismo , Moraxella catarrhalis/metabolismo , Infecciones por Moraxellaceae/metabolismo , Infecciones del Sistema Respiratorio/metabolismo , Zinc/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Animales , Proteínas Portadoras/genética , Línea Celular , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Humanos , Ratones , Ratones Endogámicos BALB C , Moraxella catarrhalis/genética , Moraxella catarrhalis/patogenicidad , Infecciones por Moraxellaceae/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sistema Respiratorio/metabolismo , Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/genética , Infecciones del Sistema Respiratorio/microbiología , Virulencia/genéticaRESUMEN
INTRODUCTION: Sparse recent data are available in the United States regarding the pathogens of acute otitis media (AOM) most likely to be recovered from children recently treated with the two most frequently prescribed antibiotics, amoxicillin or amoxicillin/clavulanate (AMC). METHODS: Of the 704 rural Kentucky children with culture-positive AOM who underwent a single tympanocentesis or culture of otorrhea between 1992 and 1998, 96 pathogens were recovered from 90 children during therapy or within 7 days posttherapy with an aminopenicillin. Identification and susceptibility testing of AOM pathogens were performed by routine National Committee for Clinical Laboratory Standards methods. RESULTS: Pathogens recovered from children with AOM recently treated (0 to 7 days) with amoxicillin (n = 38) and AMC (n = 58), respectively, were as follows: Haemophilus influenzae (beta-lactamase-negative), 16 and 29%; H. influenzae (beta-lactamase-positive), 11 and 22%; penicillin-susceptible Streptococcus pneumoniae, 26 and 12%; intermediately penicillin-nonsusceptible S. pneumoniae (PNSP), 20 and 10%; resistant PNSP 13 and 17%; Moraxella catarrhalis (beta-lactamase-positive), 13 and 7%; and Streptococcus pyogenes, 3 and 2%. H. influenzae was also isolated from 8 (75%) of 12 children treated with high dose AMC ( approximately 80 mg/kg/day amoxicillin component). Significantly fewer children recently treated with amoxicillin were otitis-prone than those given AMC (24% vs. 74%, P < 0.0001). CONCLUSIONS: The predominant pathogen recovered from children with AOM recently treated with amoxicillin was S. pneumoniae (59%) rather than beta-lactamase-producing organisms (24%). H. influenzae was the predominant (51%) pathogen, rather than PNSP (27%), recovered from children recently treated with AMC.
Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Amoxicilina/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Otitis Media con Derrame/tratamiento farmacológico , Otitis Media con Derrame/microbiología , Penicilinas/uso terapéutico , Enfermedad Aguda , Adolescente , Amoxicilina/farmacología , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Niño , Preescolar , Farmacorresistencia Bacteriana Múltiple , Quimioterapia Combinada/farmacología , Femenino , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/patogenicidad , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Moraxella catarrhalis/patogenicidad , Penicilinas/farmacología , Estudios Retrospectivos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/patogenicidad , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/patogenicidad , Resistencia betalactámicaRESUMEN
La celulitis orbitaria comprende dos patologías bien diferenciadas desde un punto de vista anatomoclínico: la forma preseptal y la postseptal. Constituye una enfermedad infecciosa relativamente frecuente en la edad pediátrica que, normalmente, es secundaria a sinusitis. Presentamos una revisión de esta patología haciendo especial hincapié en el cambio etiológico acontecido en la última década tras la vacunación sistemática contra Haemophilus influenzae tipo B. (AU)