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Pertussis Toxin and Adenylate Cyclase Toxin Provide a One-Two Punch for Establishment of Bordetella pertussis Infection of the Respiratory Tract

机译：百日咳毒素和腺苷酸环化酶毒素为建立百日咳博德特氏菌感染呼吸道提供了一两次冲床

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Previously we found that pertussis toxin (PT), an exotoxin virulence factor produced by Bordetella pertussis, plays an important early role in colonization of the respiratory tract by this pathogen, using a mouse intranasal infection model. In this study, we examined the early role played by another exotoxin produced by this pathogen, adenylate cyclase toxin (ACT). By comparing a wild-type strain to a mutant strain (ΔCYA) with an in-frame deletion of the cyaA gene encoding ACT, we found that the lack of ACT confers a significant peak (day 7) colonization defect (1 to 2 log10). In mixed-infection experiments, the ΔCYA strain was significantly outcompeted by the wild-type strain, and intranasal administration of purified ACT did not increase colonization by ΔCYA. These data suggest that ACT benefits the bacterial cells that produce it and, unlike PT, does not act as a soluble factor benefiting the entire infecting bacterial population. Comparison of lower respiratory tract infections over the first 4 days after inoculation revealed that the colonization defect of the PT deletion strain was apparent earlier than that of ΔCYA, suggesting that PT plays an earlier role than ACT in the establishment of B. pertussis infection. Examination of cells in the bronchoalveolar lavage fluid of infected mice revealed that, unlike PT, ACT does not appear to inhibit neutrophil influx to the respiratory tract early after infection but may combat neutrophil activity once influx has occurred.
机译：以前，我们发现百日咳毒素（PT）是百日咳博德特氏菌产生的一种外毒素毒力因子，使用小鼠鼻内感染模型在该病原体的呼吸道定植中起着重要的早期作用。在这项研究中，我们检查了由这种病原体产生的另一种外毒素，腺苷酸环化酶毒素（ACT）的早期作用。通过将野生型菌株与突变型菌株（ΔCYA）进行框内编码ACT的 cyaA 基因缺失进行比较，我们发现缺少ACT会导致显着的峰化（第7天）缺陷（1到2 log 10 ）。在混合感染实验中，野生型菌株明显优于ΔCYA菌株，鼻内施用纯化的ACT不会增加ΔCYA的定殖。这些数据表明，ACT有益于产生它的细菌细胞，与PT不同，它不作为使整个感染细菌种群受益的可溶性因子。接种后头4天对下呼吸道感染的比较显示，PT缺失菌株的定植缺陷明显早于ΔCYA的定植缺陷，这表明PT在建立 B方面比ACT发挥作用更早。百日咳感染。对感染小鼠的支气管肺泡灌洗液中的细胞进行检查后发现，与PT不同，ACT似乎并未抑制感染后早期中性粒细胞向呼吸道的流入，但是一旦发生，可能会抑制中性粒细胞的活性。

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