Undercover Agents of Infection: The Stealth Strategies of T4SS-Equipped Bacterial Pathogens

Bienvenu, Arthur; Martínez, Eric; Bonazzi, Matteo

doi:10.3390/toxins13100713

Cited by 6 publications

(4 citation statements)

References 99 publications

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“…The volume of the recent knowledge of the stealthing mechanisms brucellae apply to modulate the host immune system in order to prevent inflammation at the site of infection, to avoid phagocytosis, to inhibit apoptosis of the host cells, and to inhibit cytokine response, etc., is substantially greater than the volume and the ambition of this paper; thus, we will focus on the antibody response only [ 7 , 8 , 34 , 38 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

False Positives in Brucellosis Serology: Wrong Bait and Wrong Pond?

Bányász

Antal²,

Jankovics

2023

TropicalMed

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This review summarizes the status of resolving the problem of false positive serologic results (FPSR) in Brucella serology, compiles our knowledge on the molecular background of the problem, and highlights some prospects for its resolution. The molecular basis of the FPSRs is reviewed through analyzing the components of the cell wall of Gram-negative bacteria, especially the surface lipopolysaccharide (LPS) with details related to brucellae. After evaluating the efforts that have been made to solve target specificity problems of serologic tests, the following conclusions can be drawn: (i) resolving the FPSR problem requires a deeper understanding than we currently possess, both of Brucella immunology and of the current serology tests; (ii) the practical solutions will be as expensive as the related research; and (iii) the root cause of FPSRs is the application of the same type of antigen (S-type LPS) in the currently approved tests. Thus, new approaches are necessary to resolve the problems stemming from FPSR. Such approaches suggested by this paper are: (i) the application of antigens from R-type bacteria; or (ii) the further development of specific brucellin-based skin tests; or (iii) the application of microbial cell-free DNA as analyte, whose approach is detailed in this paper.

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Section: Discussionmentioning

confidence: 99%

False Positives in Brucellosis Serology: Wrong Bait and Wrong Pond?

Bányász

Antal²,

Jankovics

2023

TropicalMed

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“…The bacterial type IV secretion systems (T4SSs) comprise a functionally and structurally diverse superfamily of macromolecular translocators [1][2][3]. In Gram-negative bacteria, most T4SSs consist of three major substructures, the substrate receptor or type IV coupling protein (T4CP), an inner membrane complex (IMC), and an outer membrane core complex (OMCC) [4,5].…”

Section: Introductionmentioning

confidence: 99%

Chimeric systems composed of swapped Tra subunits between distantly-related F plasmids reveal striking plasticity among type IV secretion machines

Kishida,

Li,

Ogawa-Kishida

et al. 2024

PLoS Genet

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Bacterial type IV secretion systems (T4SSs) are a versatile family of macromolecular translocators, collectively able to recruit diverse DNA and protein substrates and deliver them to a wide range of cell types. Presently, there is little understanding of how T4SSs recognize substrate repertoires and form productive contacts with specific target cells. Although T4SSs are composed of a number of conserved subunits and adopt certain conserved structural features, they also display considerable compositional and structural diversity. Here, we explored the structural bases underlying the functional versatility of T4SSs through systematic deletion and subunit swapping between two conjugation systems encoded by the distantly-related IncF plasmids, pED208 and F. We identified several regions of intrinsic flexibility among the encoded T4SSs, as evidenced by partial or complete functionality of chimeric machines. Swapping of VirD4-like TraD type IV coupling proteins (T4CPs) yielded functional chimeras, indicative of relaxed specificity at the substrate—TraD and TraD—T4SS interfaces. Through mutational analyses, we further delineated domains of the TraD T4CPs contributing to recruitment of cognate vs heterologous DNA substrates. Remarkably, swaps of components comprising the outer membrane core complexes, a few F-specific subunits, or the TraA pilins supported DNA transfer in the absence of detectable pilus production. Among sequenced enterobacterial species in the NCBI database, we identified many strains that harbor two or more F-like plasmids and many F plasmids lacking one or more T4SS components required for self-transfer. We confirmed that host cells carrying co-resident, non-selftransmissible variants of pED208 and F elaborate chimeric T4SSs, as evidenced by transmission of both plasmids. We propose that T4SS plasticity enables the facile assembly of functional chimeras, and this intrinsic flexibility at the structural level can account for functional diversification of this superfamily over evolutionary time and, on a more immediate time-scale, to proliferation of transfer-defective MGEs in nature.

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“…Both, T3- and T4SSs span the inner and outer bacterial membrane and protrude from the bacterial surface. Upon contact with a host cell, a pore is formed in the host cell membrane at the tip of the secretion system, which creates a connection from the pathogen to the host cell, enabling it to translocate effector proteins directly into the host cell cytosol, where they subvert cell signaling pathways in favor of bacterial survival and persistence ( Dean, 2011 ; Green and Mecsas, 2016 ; Bienvenu et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems

Blasey

Rehrmann²,

Riebisch³

et al. 2023

Front. Cell. Infect. Microbiol.

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Infections caused by Gram-negative pathogens pose a major health burden. Both respiratory and gastrointestinal infections are commonly associated with these pathogens. With the increase in antimicrobial resistance (AMR) over the last decades, bacterial infections may soon become the threat they have been before the discovery of antibiotics. Many Gram-negative pathogens encode virulence-associated Type III and Type IV secretion systems, which they use to inject bacterial effector proteins across bacterial and host cell membranes into the host cell cytosol, where they subvert host cell functions in favor of bacterial replication and survival. These secretion systems are essential for the pathogens to cause disease, and secretion system mutants are commonly avirulent in infection models. Hence, these structures present attractive targets for anti-virulence therapies. Here, we review previously and recently identified inhibitors of virulence-associated bacterial secretions systems and discuss their potential as therapeutics.

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Undercover Agents of Infection: The Stealth Strategies of T4SS-Equipped Bacterial Pathogens

Cited by 6 publications

References 99 publications

False Positives in Brucellosis Serology: Wrong Bait and Wrong Pond?

False Positives in Brucellosis Serology: Wrong Bait and Wrong Pond?

Chimeric systems composed of swapped Tra subunits between distantly-related F plasmids reveal striking plasticity among type IV secretion machines

Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems

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