Trovão Liana de Oliveira, Vieira Mônica Aparecida Midolli, Santos Ana Carolina de Mello, Puño-Sarmiento Juan Josue, Nunes Pedro Henrique Soares, Santos Fernanda Fernandes, Rocha Victória Galdino Pavlenco, Knöbl Terezinha, Navarro-Garcia Fernando, Gomes Tânia Aparecida Tardelli
Laboratório Experimental de Patogenicidade de Enterobactérias, Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Laboratório Alerta, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Front Cell Infect Microbiol. 2024 Dec 4;14:1393369. doi: 10.3389/fcimb.2024.1393369. eCollection 2024.
Enteropathogenic (EPEC) strains are subdivided into typical (tEPEC) and atypical (aEPEC) according to the presence or absence of a virulence-associated plasmid called pEAF. Our research group has previously demonstrated that two aEPEC strains, 0421-1 and 3991-1, induce an increase in mucus production in a rabbit ileal loop model . This phenomenon was not observed with a tEPEC prototype strain. Few studies on aEPEC strains evaluating their capacity to induce intestinal mucus hypersecretion were done. This study aimed to investigate aEPEC strains regarding their genotypic and phenotypic characteristics, their ability to alter mucus production in an intestinal infection model, and their potential mucinolytic activity. To investigate the relationship between strains 0421-1 and 3991-1 and 11 other aEPEC strains, their serotypes, sequence types (ST), and virulence factors (VF), several sequencing and genomic analyses were carried out. The study also involved researching the reproduction of mucus hypersecretion in rabbits . We found that the two mucus-inducing strains and two other strains (1582-4 and 2531-13) shared the same phylogroup (A), ST (378), serotype (O101/O162:H33), and intimin subtype (ι2), were phylogenetically related, and induced mucus hypersecretion . A wide diversity of VFs was found among the strains, confirming their genomic heterogeneity. However, among the genes studied, no unique virulence factor or gene set was identified exclusively in the mucus-inducing strains, suggesting the multifactorial nature of this phenomenon. The two strains (1582-4 and 2531-13) closely related to the two aEPEC strains that induced mucus production also induced the phenomenon. The investigation of the mucinolytic activity revealed that all aEPEC strains used mucins as their carbon sources. Ten of the 13 aEPEC strains could cross a mucin layer, and only four adhered better to agar containing mucin than to agar without mucin. The present study paves the way for subsequent investigations into the molecular mechanisms regarding cellular interactions and responses, as well as the correlation between virulence factors and the induction of mucus production/expression during aEPEC infections.
肠道致病性大肠杆菌(EPEC)菌株根据是否存在一种名为pEAF的毒力相关质粒,可分为典型(tEPEC)和非典型(aEPEC)两类。我们的研究小组此前已证明,两株aEPEC菌株0421 - 1和3991 - 1在兔回肠袢模型中可诱导黏液分泌增加。而tEPEC原型菌株未观察到这种现象。关于aEPEC菌株诱导肠道黏液分泌过多能力的研究较少。本研究旨在调查aEPEC菌株的基因型和表型特征、它们在肠道感染模型中改变黏液分泌的能力以及它们潜在的黏蛋白分解活性。为了研究0421 - 1和3991 - 1菌株与其他11株aEPEC菌株之间的关系、它们的血清型、序列类型(ST)和毒力因子(VF),进行了多项测序和基因组分析。该研究还包括研究兔黏液分泌过多的重现情况。我们发现,两株诱导黏液分泌的菌株以及另外两株菌株(1582 - 4和2531 - 13)具有相同的系统发育群(A)、ST(378)、血清型(O101/O162:H33)和紧密素亚型(ι2),它们在系统发育上相关,并诱导黏液分泌过多。在这些菌株中发现了多种毒力因子,证实了它们的基因组异质性。然而,在所研究的基因中,未发现仅在诱导黏液分泌的菌株中存在的独特毒力因子或基因集,这表明该现象具有多因素性质。与两株诱导黏液分泌的aEPEC菌株密切相关的两株菌株(1582 - 4和2531 - 13)也诱导了这种现象。对黏蛋白分解活性的研究表明,所有aEPEC菌株都以黏蛋白作为碳源。13株aEPEC菌株中有10株能够穿过黏蛋白层,只有4株在含黏蛋白的琼脂上比在不含黏蛋白的琼脂上黏附性更好。本研究为后续关于细胞相互作用和反应的分子机制以及aEPEC感染期间毒力因子与黏液产生/表达诱导之间相关性的研究铺平了道路。