Publication: Mecanismo de patogenicidad de "Streptococcus pneumoniae" asociados a enfermedad invasiva y enfermedad pulmonar obstructiva crónica
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2017-11-30
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Universidad Complutense de Madrid
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Abstract
Streptococcus pneumoniae, también conocido como neumococo, es uno de los patógenos humanos más importantes responsable de infecciones severas tales como neumonía bacteriémica y meningitis, así como de enfermedades no tan graves como neumonía adquirida en la comunidad, otitis media aguda, sinusitis y conjuntivitis (Bogaert et al., 2004), que afectan principalmente a niños, personas mayores de 65 años y pacientes inmunocomprometidos (Koedel et al., 2002; van der Poll y Opal, 2009). La enfermedad neumocócica es precedida por la colonización de la nasofaringe, que es particularmente común en niños con más de un serotipo colonizando simultáneamente (Bogaert et al., 2004). Se calcula que la tercera parte de las muertes anuales que se producen en el mundo son debidas a enfermedades infecciosas y, entre todas ellas, las enfermedades respiratorias son las responsables de la muerte de 4 millones de personas cada año (Morens et al., 2004). Según la Organización Mundial de la Salud (OMS), la sepsis, la neumonía neonatal y la neumonía comunitaria en niños más mayores fueron responsables del 15% de las casi un millón de muertes anuales en niños menores de 5 años ocurridas en el 2015, siendo S. pneumoniae el causante más frecuente de neumonía infantil severa, tanto en países desarrollados como en aquellos en vías de desarrollo (OMS, 2016; UNICEF, 2015; UNICEF y WHO, 2006). La capsula polisacarídica está considerada como uno de los principales factores de virulencia de la bacteria (López y García, 2004), de la cual se han descrito más de 96 polisacáridos capsulares (CPS) diferentes (Jauneikaite et al., 2015). Las vacunas conjugadas existentes, como son la PCV7, PCV10 y PCV13, confieren protección frente a la enfermedad neumocócica invasiva (ENI) (Feikin et al., 2013; O'Brien y Levine, 2006). La activación de la cascada del complemento por anticuerpos específicos conduce a la formación del componente clave C3b, el cual juega un papel crucial en la defensa del hospedador frente a neumococo, recubriendo los microorganismos y estimulando la fagocitosis. Sin embargo, uno de los inconvenientes de las vacunas conjugadas es el limitado número de serotipos frente a los que protegen y, como consecuencia de la introducción de las mismas, el fenómeno conocido como reemplazo de serotipos o “capsular switching” (Coffey et al., 1991), que permite a los clones preexistentes de S. pneumoniae que expresan serotipos vacunales escapar de la inmunidad inducida por la vacunación mediante la adquisición de genes capsulares de neumococo no incluidos en las vacunas (Brueggemann et al., 2007; Golubchik et al., 2012)...
Streptococcus pneumoniae, the pneumococcus, is an important human pathogen that usually colonizes asymptomatically the mucosal surfaces of the upper respiratory tract in early childhood with more than one serotype colonizing the nasopharynx of the same individual at the same time (Bogaert et al., 2004). Once carriage is established, the microorganism may invade several sterile sites, leading to what is known as invasive pneumococcal disease (IPD). Indeed, the pneumococcus is one of the major etiologic agents causing episodes of communityacquired pneumonia, bacteremia and meningitis. However, S. pneumoniae is also a major cause of non-invasive diseases such as non-bacteraemic pneumonia, acute otitis media, sinusitis and conjunctivitis, mainly in children, the elderly, and immunocompromised patients (Henriques- Normark and Tuomanen, 2013). More than 25% of the 57 million annual deaths worldwide are estimated to be directly related to infectious diseases. Particularly, respiratory infections are responsible of the death of 4 million people every year. According to the World Health Organization (WHO), estimates of sepsis or pneumonia in neonates and also pneumonia in older children accounted for 15% of the nearly 1 million deaths of children younger than 5 years old reported in 2015, being Streptococcus pneumoniae the most common cause of severe pneumonia among children in more and less developed countries (OMS, 2016; UNICEF, 2015; UNICEF and WHO, 2006). The capsule is considered the main pneumococcal virulence factor and up to 96% distinct capsular polysaccharides (CPS) have been described (Jauneikaite et al., 2015). Current prophylactic measures against pneumococcal infections such as the introduction of PCV7, PCV10 and PCV13, are a highly efficient approach for preventing IPD. Activation of complement cascades by specific antibodies leads to the formation of C3b, the key complement component that is crucial in host defense against pneumococcus by coating the microorganism and stimulating phagocytosis (Markieswski and Lambris, 2007). However, among the main disadvantages of conjugated vaccines are the limited number of serotypes covered and the phenomenon known as “capsular switching” (Coffey et al., 1991) which allows pre-existing clones of S. pneumoniae expressing vaccine serotypes to escape vaccine-induced immunity by acquisition of capsular genes from non-vaccine serotypes (Brueggemann et al., 2007; Golubchik et al., 2012)...
Streptococcus pneumoniae, the pneumococcus, is an important human pathogen that usually colonizes asymptomatically the mucosal surfaces of the upper respiratory tract in early childhood with more than one serotype colonizing the nasopharynx of the same individual at the same time (Bogaert et al., 2004). Once carriage is established, the microorganism may invade several sterile sites, leading to what is known as invasive pneumococcal disease (IPD). Indeed, the pneumococcus is one of the major etiologic agents causing episodes of communityacquired pneumonia, bacteremia and meningitis. However, S. pneumoniae is also a major cause of non-invasive diseases such as non-bacteraemic pneumonia, acute otitis media, sinusitis and conjunctivitis, mainly in children, the elderly, and immunocompromised patients (Henriques- Normark and Tuomanen, 2013). More than 25% of the 57 million annual deaths worldwide are estimated to be directly related to infectious diseases. Particularly, respiratory infections are responsible of the death of 4 million people every year. According to the World Health Organization (WHO), estimates of sepsis or pneumonia in neonates and also pneumonia in older children accounted for 15% of the nearly 1 million deaths of children younger than 5 years old reported in 2015, being Streptococcus pneumoniae the most common cause of severe pneumonia among children in more and less developed countries (OMS, 2016; UNICEF, 2015; UNICEF and WHO, 2006). The capsule is considered the main pneumococcal virulence factor and up to 96% distinct capsular polysaccharides (CPS) have been described (Jauneikaite et al., 2015). Current prophylactic measures against pneumococcal infections such as the introduction of PCV7, PCV10 and PCV13, are a highly efficient approach for preventing IPD. Activation of complement cascades by specific antibodies leads to the formation of C3b, the key complement component that is crucial in host defense against pneumococcus by coating the microorganism and stimulating phagocytosis (Markieswski and Lambris, 2007). However, among the main disadvantages of conjugated vaccines are the limited number of serotypes covered and the phenomenon known as “capsular switching” (Coffey et al., 1991) which allows pre-existing clones of S. pneumoniae expressing vaccine serotypes to escape vaccine-induced immunity by acquisition of capsular genes from non-vaccine serotypes (Brueggemann et al., 2007; Golubchik et al., 2012)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Microbiología III, leída el 16-06-2017