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

The opportunistic pathogen Stenotrophomonas maltophilia utilizes a type IV secretion system for interbacterial killing

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Author(s):
Bayer-Santos, Ethel [1, 2] ; Cenens, William [1] ; Matsuyama, Bruno Yasui [1] ; Oka, Gabriel Umaji [1] ; Di Sessa, Giancarlo [1] ; Mininel, Izabel Del Valle [1] ; Alves, Tiago Lubiana [1] ; Farah, Chuck Shaker [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: PLOS PATHOGENS; v. 15, n. 9 SEP 2019.
Web of Science Citations: 1
Abstract

Bacterial type IV secretion systems (T4SS) are a highly diversified but evolutionarily related family of macromolecule transporters that can secrete proteins and DNA into the extracellular medium or into target cells. It was recently shown that a subtype of T4SS harboured by the plant pathogen Xanthomonas citri transfers toxins into target cells. Here, we show that a similar T4SS from the multi-drug-resistant opportunistic pathogen Stenotrophomonas maltophilia is proficient in killing competitor bacterial species. T4SS-dependent duelling between S. maltophilia and X. citri was observed by time-lapse fluorescence microscopy. A bioinformatic search of the S. maltophilia K279a genome for proteins containing a C-terminal domain conserved in X. citri T4SS effectors (XVIPCD) identified twelve putative effectors and their cognate immunity proteins. We selected a putative S. maltophilia effector with unknown function (Smlt3024) for further characterization and confirmed that it is indeed secreted in a T4SS-dependent manner. Expression of Smlt3024 in the periplasm of E. coli or its contact-dependent delivery via T4SS into E. coli by X. citri resulted in reduced growth rates, which could be counteracted by expression of its cognate inhibitor Smlt3025 in the target cell. Furthermore, expression of the VirD4 coupling protein of X. citri can restore the function of S. maltophilia Delta virD4, demonstrating that effectors from one species can be recognized for transfer by T4SSs from another species. Interestingly, Smlt3024 is homologous to the N-terminal domain of large Ca2+-binding RTX proteins and the crystal structure of Smlt3025 revealed a topology similar to the iron-regulated protein FrpD from Neisseria meningitidis which has been shown to interact with the RTX protein FrpC. This work expands our current knowledge about the function of bacteria-killing T4SSs and increases the panel of effectors known to be involved in T4SS-mediated interbacterial competition, which possibly contribute to the establishment of S. maltophilia in clinical and environmental settings. Author summary Competition between microorganisms determines which species will dominate or be eradicated from a specific habitat. Bacteria use a series of mechanisms to kill or prevent multiplication of competitors. We show that an opportunistic pathogen, Stenotrophomonas maltophilia, harbours a type IV secretion system (T4SS) that works as a weapon to kill competitor bacterial species. We identified a series of new putative toxic T4SS effectors secreted by S. maltophilia and their cognate immunity proteins. Characterization of one S. maltophilia effector with unknown function (Smlt3024) shows that it reduces growth rate of E. coli cells. Its cognate immunity protein, Smlt3025, presents a structure similar to the FrpD lipoprotein from Neisseria meningitidis. Smlt3024 expressed in the plant pathogen Xanthomonas citri can be translocated into E. coli cells, highlighting the interchangeable characteristic of T4SSs toxins and the conservation of secretion system function. We show that X. citri and S. maltophilia can kill each other in a T4SS-dependent manner, most likely due to differences in their cohorts of effector-immunity protein pairs. This work expands our current knowledge about the function of bacteria-killing T4SSs and the bacterial arsenal fired by these systems during encounters with other species. (AU)

FAPESP's process: 18/04553-8 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells
Grantee:Ethel Bayer Santos
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 17/17303-7 - Structure and function of bacterial secretion systems
Grantee:Shaker Chuck Farah
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/18237-2 - Genetic elucidation of the functional and regulatory mechanisms underlying the Type IV Secretion System in Xanthomonas citri and how it mediates contact dependent killing
Grantee:William Cenens
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/00458-5 - Structural and functional characterization of Xanthomonas citri type IV secretion system.
Grantee:Bruno Yasui Matsuyama
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/07777-5 - Cyclic di-GMP signaling and the Type IV macromolecule secretion system in Xanthomonas citri
Grantee:Shaker Chuck Farah
Support type: Research Projects - Thematic Grants
FAPESP's process: 17/02178-2 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells
Grantee:Ethel Bayer Santos
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 15/25381-2 - Study of the role of type IV secretion system of Xanthomonas citri and Stenotrophomonas maltophilia in the interaction with Dictyostelium discoideum.
Grantee:Ethel Bayer Santos
Support type: Scholarships in Brazil - Post-Doctorate