Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

EspFu-Mediated Actin Assembly Enhances Enteropathogenic Escherichia coli Adherence and Activates Host Cell Inflammatory Signaling Pathways

Full text
Martins, Fernando H. [1, 2, 3] ; Kumar, Ashwani [4] ; Abe, Cecilia M. [1] ; Carvalho, Eneas [1] ; Nishiyama-Jr, Milton ; Xing, Chao [4, 5, 6] ; Sperandio, Vanessa [2, 3] ; Elias, Waldir P. [1]
Total Authors: 8
[1] Butantan Inst, Lab Bacteriol, Sao Paulo - Brazil
[2] Univ Texas Southwestern Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 - USA
[3] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 - USA
[4] Univ Texas Southwestern Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 - USA
[5] Univ Texas Southwestern Med Ctr Dallas, Dept Bioinformat, Dallas, TX 75390 - USA
[6] Univ Texas Southwestern Med Ctr Dallas, Dept Populat & Data Sci, Dallas, TX 75390 - USA
Total Affiliations: 6
Document type: Journal article
Source: MBIO; v. 11, n. 2 MAR-APR 2020.
Web of Science Citations: 0

The translocation of effectors into the host cell through type 3 secretion systems (T3SS) is a sophisticated strategy employed by pathogenic bacteria to subvert host responses and facilitate colonization. Enteropathogenic Escherichia coil (EPEC) and enterohemorrhagic E. coli (EHEC) utilize the Tir and EspFu (also known as TccP) effectors to remodel the host cytoskeleton, culminating in the formation of attaching and effacing (AE) lesions on enterocytes. While some EPEC strains require tyrosine phosphorylation of Tir and recruitment of the host Nck to trigger actin polymerization, EHEC and certain EPEC strains, whose Tir is not phosphorylated, rely on the effector EspFu for efficient actin remodeling. Here, we investigated the role played by Tir-Nck and Tir-EspFu actin polymerization pathways during the infection of epithelial cells, as well as the host transcriptional response to the AE lesion formation induced by EPEC. We found that EspFu-mediated actin assembly promotes bacterial attachment and epithelial colonization more efficiently than Tir-Nck. Moreover, we showed that both actin polymerization mechanisms can activate inflammatory pathways and reverse the anti-inflammatory response induced by EPEC in epithelial cells. However, this activity is remarkably more evident in infections with EspFu-expressing EPEC strains. This study demonstrates the complex interactions between effector-mediated actin remodeling and inflammation. Different strains carry different combinations of these two effectors, highlighting the plasticity of pathogenic E. coli enteric infections. IMPORTANCE EPEC is among the leading causes of diarrheal disease worldwide. The colonization of the gut mucosa by EPEC results in actin pedestal formation at the site of bacterial attachment. These pedestals are referred to as attaching and effacing (AE) lesions. Here, we exploit the different molecular mechanisms used by EPEC to induce AE lesions on epithelial cells, showing that the effector EspFu is associated with increased bacterial attachment and enhanced epithelial colonization compared to the Tir-Nck pathway. Moreover, we also showed that actin pedestal formation can counterbalance the anti-inflammatory activity induced by EPEC, especially when driven by EspFu. Collectively, our findings provide new insights into virulence mechanisms employed by EPEC to colonize epithelial cells, as well as the host response to this enteric pathogen. (AU)

FAPESP's process: 11/14103-0 - Biological activities of the autotransporter protein PIC of atypical enteropathogenic Escherichia coli
Grantee:Waldir Pereira Elias Junior
Support Opportunities: Regular Research Grants
FAPESP's process: 16/08401-2 - Dynamics of pedestal formation by atypical Enteropathogenic Escherichia coli strains displaying distinct actin polymerization pathways
Grantee:Fernando Henrique Martins
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 13/17403-0 - Role of EspFu protein on atypical enteropathogenic Escherichia coli
Grantee:Fernando Henrique Martins
Support Opportunities: Scholarships in Brazil - Doctorate