Summary
Pseudomonas aeruginosa is currently the major cause of morbidity and mortality in cystic fibrosis. Studies to understand why this particular organism is a problem and why host defenses fail to clear it, are beginning to provide some answers. Implicit in any working hypothesis are the prerequisites that: (i)P. aeruginosa should have a tropism for the respiratory tract; (ii) there should be a physical clearance defect; and (iii) there should be an acquired immune clearance defect. Studies from many laboratories support these contentions. This organism exhibits its tropism by adhering to tracheal cells and to tracheobronchial mucins by means of pili or the mucoid exopolysac-charide of mucoid strains. The receptors on both cells and mucins contain sialic acid as the dominant sugar moiety. Many factors contribute to its persistence, chief among which is the failure of phagocytic defenses caused by microbial or host enzymes and even by mucins which inhibit the opsonophagocytosis ofP. aeruginosa. Injury to the mucociliary system, again caused by microbial or host factors, is also a prominent factor in the persistence ofP. aeruginosa. We hypothesize that this organism is the dominant pathogen because of the existence of receptors in the respiratory tract for it and that it persists because bacteria in stagnant mucus cannot be cleared physically or immunologically. We are doubtful that conventional vaccination approaches will yield a solution to this problem.
Zusammenfassung
Pseudomonas aeruginosa ist zur Zeit die wichtigste Krankheits-und Todesursache bei Patienten mit zystischer Fibrose. Studien, die sich mit den Problemen befassen, die dieser spezielle Erreger verursacht, und mit der Frage, warum er durch Abwehrmechanismen des Wirtes nicht eliminiert wird, geben die ersten Antworten zu diesem Thema. Die Arbeitshypothesen gehen davon aus, daß 1.P. aeruginosa eine besondere Neigung hat, sich im Respirationstrakt anzusiedeln; 2. ein Defekt in der physikalischen Klärfunktion besteht und es 3. einen erworbenen Defekt in der immunologischen Komponente der Erregeradikation gibt. Diese Annahmen werden durch Laboruntersuchungen gestützt. Die Adhärenz des Erregers an Trachealzellen und an tracheobronchialen Muzinen mittels Pili oder dem mukoiden Exopolysaccharid mukoider Stämme ist die Grundlage für seinen Tropismus zum Tracheobronchialbaum. Die Rezeptoren beider Zellen und Muzine enthalten Sialinsäure als dominierende Zuckerverbindung. Zahlreiche Faktoren begünstigen die Persistenz des Erregers; am bedeutsamsten ist das Versagen der phagozytären Abwehr unter dem Einfluß von Enzymen, die vom Mikroorganismus oder dem Wirt selbst sezerniert werden, und sogar auch der Muzine, die die Opsonophagozytose vonP. aeruginosa hemmen. Eine Schädigung des mukoziliaren Systems, die wiederum durch mikrobielle oder Wirtsfaktoren verursacht sein kann, ist ebenfalls für die Erregerpersistenz von Bedeutung. Wir stellen die Hypothese auf, daß dieser Mikroorganismus deshalb der dominierende Erreger ist, weil der Respirationstrakt Rezeptoren für ihn besitzt; die Ursache für seine Persistenz liegt darin, daß die Bakterien im stagnierenden Schleim weder physikalisch noch immunologisch beseitigt werden können. Wir bezweifeln, daß sich mit konventionellen Versuchen einer Vakzination eine Lösung für dieses Problem finden läßt.
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Ramphal, R., Vishwanath, S. Why is pseudomonas the colonizer and why does it persist?. Infection 15, 281–287 (1987). https://doi.org/10.1007/BF01644139
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DOI: https://doi.org/10.1007/BF01644139