Carbonetti Nicholas H
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Curr Opin Infect Dis. 2016 Jun;29(3):287-94. doi: 10.1097/QCO.0000000000000264.
The purpose of this review is to summarize and discuss recent findings and selected topics of interest in Bordetella pertussis virulence and pathogenesis and treatment of pertussis. It is not intended to cover issues on immune responses to B. pertussis infection or problems with currently used pertussis vaccines.
Studies on the activities of various B. pertussis virulence factors include the immunomodulatory activities of filamentous hemagglutinin, fimbriae, and adenylate cyclase toxin. Recently emerging B. pertussis strains show evidence of genetic selection for vaccine escape mutants, with changes in vaccine antigen-expressing genes, some of which may have increased the virulence of this pathogen. Severe and fatal pertussis in young infants continues to be a problem, with several studies highlighting predictors of fatality, including the extreme leukocytosis associated with this infection. Treatments for pertussis are extremely limited, though early antibiotic intervention may be beneficial. Neutralizing pertussis toxin activity may be an effective strategy, as well as targeting two host proteins, pendrin and sphingosine-1-phosphate receptors, as novel potential therapeutic interventions.
Pertussis is reemerging as a major public health problem and continued basic research is revealing information on bacterial virulence and disease pathogenesis, as well as potential novel strategies for vaccination and targets for therapeutic intervention.
本综述旨在总结和讨论百日咳博德特氏菌毒力、发病机制及百日咳治疗方面的最新研究发现和选定的感兴趣主题。本综述不涉及对百日咳博德特氏菌感染的免疫反应问题或当前使用的百日咳疫苗相关问题。
对多种百日咳博德特氏菌毒力因子活性的研究包括丝状血凝素、菌毛和腺苷酸环化酶毒素的免疫调节活性。最近出现的百日咳博德特氏菌菌株显示出疫苗逃逸突变体的基因选择证据,疫苗抗原表达基因发生了变化,其中一些可能增加了该病原体的毒力。婴儿严重和致命性百日咳仍然是一个问题,多项研究强调了死亡预测因素,包括与这种感染相关的极度白细胞增多。百日咳的治疗方法极为有限,不过早期抗生素干预可能有益。中和百日咳毒素活性可能是一种有效策略,以及将两种宿主蛋白——pendrin和鞘氨醇-1-磷酸受体作为新型潜在治疗干预靶点。
百日咳正再次成为一个主要的公共卫生问题,持续的基础研究正在揭示有关细菌毒力和疾病发病机制的信息,以及潜在的新型疫苗接种策略和治疗干预靶点。