A bacterial conjugation machinery recruited for pathogenesis

Abstract

SummaryType IV secretion systems (T4SS) are multicomponent transporters of Gram-negative bacteria adapted to functions as diverse as DNA transfer in bacterial conjugation or the delivery of effector proteins into eukaryotic target cells in pathogenesis. The generally modest sequence conservation between T4SS may reflect their evolutionary distance and/or functional divergence. Here, we show that the establishment of intraerythrocytic parasitism by Bartonella tribocorum requires a putative T4SS, which shares an unprecedented level of sequence identity with the Trw conjugation machinery of the broad-host-range antibiotic resistance plasmid R388 (up to 80% amino acid identity for individual T4SS components). The highly conserved T4SS loci are collinear except for the presence of numerous tandem gene duplications in B. tribocorum , which mostly encode variant forms of presumed surface-exposed pilus subunits. Conservation is not only structural, but also functional: R388 mutated in either trwD or trwH encoding essential T4SS components could be trans -complemented for conjugation by the homologues of the B. tribocorum system. Conservation also includes the transcription regulatory circuit: both T4SS loci encode a highly homologous and interchangeable KorA/KorB repressor system that negatively regulates the expression of all T4SS components. This striking example of adaptive evolution reveals the capacity of T4SS to assume dedicated functions in either DNA transfer or pathogenesis over rather short evolutionary distance and implies a novel role for the conjugation systems of widespread broad-host-range plasmids in the evolution of bacterial pathogens.

Strategies of exploitation of mammalian reservoirs by Bartonella species

“…Trw is the third T4SS found in bartonellae, and its importance in the establishment of intra-erythrocytic infections by bartonellae in reservoir hosts has been recognised for some time [63-65]. However, evidence for the direct role of Trw in erythrocyte infection has been only recently obtained following the development of an in vitro model for erythrocyte adherence and invasion [19].…”

“…Unlike VirB/D4, the Trw T4SS lacks the coupling protein required for export of effectors, suggesting that it is no longer a secretion system [65]. The trw genes of Bartonella species are co-linear with the respective genes of plasmid R388 except for the presence of multiple tandem gene duplications of trwL (the virB2 homolog) and trwJ-I-H (the virB5, virB6 and virB7 homologs).…”

Coupling Factors in Macromolecular Type-IV Secretion Machineries

“…They bear Walker A (motif I) and B (motif II or DExx box) NTP-binding sequences [88] and may use the energy of Rhizobium etli bacterium; N2-fixation [154] Sinorhizobium meliloti bacterium; N2-fixation [14,15,17] Shigella flexneri plasmid ColIb P9 bacterium; diarrhoea / dysentery [155] Bartonella henselae and tribocorum bacterium; cat scratch disease, bacteremia [156][157][158][159][160] Campylobacter jejuni bacterium; bacterial diarrhoea [161,162] Toxoplasma gondii protozoon; toxoplasmosis (encephalitis) [54] Leishmania donovani protozoon; leishmaniasis [54] Mycobacterium tuberculosis bacterium; tuberculosis [54] Bordetella bronchiseptica bacterium; bronchitis [14,15,17] Enterobacter aerogenes bacterium; nosocomial infections [11] Actinobacillus actinomycetemcomitans bacterium; periodontitis [14,15,17,163,164] Escherichia coli bacterium; diarrhea [11] Caulobacter crescentus bacterium; non-pathogenic [14,15,17] Coxiella burnetii bacterium; acute febrile disease, endocarditis, pneumonitis [165,166] Thiobacillus ferroxidans bacterium; iron oxidation [14,15,17] Wolbachia intracellular symbiont of arthropods; sexual alterations in host [167,168] Ralstonia eutrophantus bacterium; heavy-metal resistance [11,169] Salmonella typhi, typhimurium and enteriditis bacterium; typhus, salmonellosis …”

Bartonella and Brucella--Weapons and Strategies for Stealth Attack

“…The trw locus comprises an operon encoding a typical T4SS but as a particularity displays multiple tandem-repeated gene copies encoding variant forms of the extracellular pilus component. The Bartonella Trw T4SS is closely related to the canonical Trw conjugation system of the conjugative plasmid R388 and was thus probably gained by horizontal gene transfer (Seubert et al 2003). The Trw T4SS mediates erythrocyte adhesion of lineage 4 species in a host-specific manner.…”

“…The Trw T4SS mediates erythrocyte adhesion of lineage 4 species in a host-specific manner. The subsequent invasion process requires the invasion-associated locus, containing IalA and IalB, and/or the IalAB-independent erythrocyte invasion locus, Iiv (Seubert et al 2003;Dehio 2004;Schroder and Dehio 2005;Saenz et al 2007;VayssierTaussat et al 2010;Deng et al 2012).…”