Publications by authors named "Ian S Barton"

5 Publications

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Uncovering the Hidden Credentials of Virulence.

Microbiol Mol Biol Rev 2021 02 10;85(1). Epub 2021 Feb 10.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.

Bacteria in the genus are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world's most common zoonoses. strains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals. The brucellae maintain predominantly an intracellular lifestyle in their mammalian hosts, and their ability to subvert the host immune response and survive and replicate in macrophages and placental trophoblasts underlies their success as pathogens. We are just beginning to understand how these bacteria evolved from a progenitor alphaproteobacterium with an environmental niche and diverged to become highly host-adapted and host-specific pathogens. Two important virulence determinants played critical roles in this evolution: (i) a type IV secretion system that secretes effector molecules into the host cell cytoplasm that direct the intracellular trafficking of the brucellae and modulate host immune responses and (ii) a lipopolysaccharide moiety which poorly stimulates host inflammatory responses. This review highlights what we presently know about how these and other virulence determinants contribute to pathogenesis. Gaining a better understanding of how the brucellae produce disease will provide us with information that can be used to design better strategies for preventing brucellosis in animals and for preventing and treating this disease in humans.
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http://dx.doi.org/10.1128/MMBR.00021-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549849PMC
February 2021

Co-dependent and Interdigitated: Dual Quorum Sensing Systems Regulate Conjugative Transfer of the Ti Plasmid and the At Megaplasmid in 15955.

Front Microbiol 2020 18;11:605896. Epub 2021 Jan 18.

Department of Biology, Indiana University, Bloomington, IN, United States.

Members of the , often carry multiple secondary replicons in addition to the primary chromosome with compatible -based replication systems. Unlike secondary chromosomes and chromids, -based megaplasmids and plasmids can undergo copy number fluctuations and are capable of conjugative transfer in response to environmental signals. Several lineages harbor three secondary -based replicons, including a secondary chromosome (often linear), the Ti (tumor-inducing) plasmid and the At megaplasmid. The Ti plasmid is required for virulence and encodes a conjugative transfer () system that is strictly regulated by a subset of plant-tumor released opines and a well-described acyl-homoserine lactone (AHL)-based quorum-sensing mechanism. The At plasmids are generally not required for virulence, but carry genes that enhance rhizosphere survival, and these plasmids are often conjugatively proficient. We report that the At megaplasmid of the octopine-type strain 15955 encodes a quorum-controlled conjugation system that directly interacts with the paralogous quorum sensing system on the co-resident Ti plasmid. Both the pAt15955 and pTi15955 plasmids carry homologs of a TraI-type AHL synthase, a TraR-type AHL-responsive transcription activator, and a TraM-type anti-activator. The genes from both pTi15955 and pAt15955 can direct production of the inducing AHL (3-octanoyl-L-homoserine lactone) and together contribute to the overall AHL pool. The TraR protein encoded on each plasmid activates AHL-responsive transcription of target gene promoters. The pAt15955 TraR can cross-activate genes on the Ti plasmid as strongly as its cognate genes, whereas the pTi15955 TraR is preferentially biased toward its own genes. Putative box elements are located upstream of target promoters, and comparing between plasmids, they are in similar locations and share an inverted repeat structure, but have distinct consensus sequences. The two AHL quorum sensing systems have a combinatorial effect on conjugative transfer of both plasmids. Overall, the interactions described here have implications for the horizontal transfer and evolutionary stability of both plasmids and, in a broad sense, are consistent with other systems that often have multiple quorum-sensing controlled secondary replicons.
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http://dx.doi.org/10.3389/fmicb.2020.605896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856919PMC
January 2021

Destabilization of the Tumor-Inducing Plasmid from an Octopine-Type Lineage Drives a Large Deletion in the Co-resident At Megaplasmid.

G3 (Bethesda) 2019 10 7;9(10):3489-3500. Epub 2019 Oct 7.

Department of Biology, Indiana University, Bloomington, Indiana.

Bacteria with multi-replicon genome organizations, including members of the family , often carry a variety of niche-associated functions on large plasmids. While evidence exists for cross-replicon interactions and co-evolution between replicons in many of these systems, remarkable strain-to-strain variation is also observed for extrachromosomal elements, suggesting increased genetic plasticity. Here, we show that curing of the tumor-inducing virulence plasmid (pTi) of an octopine-type lineage leads to a large deletion in the co-resident At megaplasmid (pAt). The deletion event is mediated by a repetitive IS-element, IS66, and results in a variety of environment-dependent fitness consequences, including loss of independent conjugal transfer of the plasmid. Interestingly, a related and otherwise wild-type strain is missing exactly the same large pAt segment as the pAt deletion derivatives, suggesting a similar event over its natural history. Overall, the findings presented here uncover a novel genetic interaction between the two large plasmids of and provide evidence for cross-replicon integration and co-evolution of these plasmids.
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http://dx.doi.org/10.1534/g3.119.400554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778807PMC
October 2019

Ecological and evolutionary dynamics of a model facultative pathogen: Agrobacterium and crown gall disease of plants.

Environ Microbiol 2018 01 4;20(1):16-29. Epub 2017 Dec 4.

Division of Biology, Kansas State University, Manhattan, KS, USA.

Many important pathogens maintain significant populations in highly disparate disease and non-disease environments. The consequences of this environmental heterogeneity in shaping the ecological and evolutionary dynamics of these facultative pathogens are incompletely understood. Agrobacterium tumefaciens, the causative agent for crown gall disease of plants has proven a productive model for many aspects of interactions between pathogens and their hosts and with other microbes. In this review, we highlight how this past work provides valuable context for the use of this system to examine how heterogeneity and transitions between disease and non-disease environments influence the ecology and evolution of facultative pathogens. We focus on several features common among facultative pathogens, such as the physiological remodelling required to colonize hosts from environmental reservoirs and the consequences of competition with host and non-host associated microbiota. In addition, we discuss how the life history of facultative pathogens likely often results in ecological tradeoffs associated with performance in disease and non-disease environments. These pathogens may therefore have different competitive dynamics in disease and non-disease environments and are subject to shifting selective pressures that can result in pathoadaptation or the within-host spread of avirulent phenotypes.
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http://dx.doi.org/10.1111/1462-2920.13976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764771PMC
January 2018

Ecological dynamics and complex interactions of Agrobacterium megaplasmids.

Front Plant Sci 2014 14;5:635. Epub 2014 Nov 14.

Department of Biology, Indiana University Bloomington, IN, USA.

As with many pathogenic bacteria, agrobacterial plant pathogens carry most of their virulence functions on a horizontally transmissible genetic element. The tumor-inducing (Ti) plasmid encodes the majority of virulence functions for the crown gall agent Agrobacterium tumefaciens. This includes the vir genes which drive genetic transformation of host cells and the catabolic genes needed to utilize the opines produced by infected plants. The Ti plasmid also encodes, an opine-dependent quorum sensing system that tightly regulates Ti plasmid copy number and its conjugal transfer to other agrobacteria. Many natural agrobacteria are avirulent, lacking the Ti plasmid. The burden of harboring the Ti plasmid depends on the environmental context. Away from diseased hosts, plasmid costs are low but the benefit of the plasmid is also absent. Consequently, plasmidless genotypes are favored. On infected plants the costs of the Ti plasmid can be very high, but balanced by the opine benefits, locally favoring plasmid bearing cells. Cheating derivatives which do not incur virulence costs but can benefit from opines are favored on infected plants and in most other environments, and these are frequently isolated from nature. Many agrobacteria also harbor an At plasmid which can stably coexist with a Ti plasmid. At plasmid genes are less well characterized but in general facilitate metabolic activities in the rhizosphere and bulk soil, such as the ability to breakdown plant exudates. Examination of A. tumefaciens C58, revealed that harboring its At plasmid is much more costly than harboring it's Ti plasmid, but conversely the At plasmid is extremely difficult to cure. The interactions between these co-resident plasmids are complex, and depend on environmental context. However, the presence of a Ti plasmid appears to mitigate At plasmid costs, consistent with the high frequency with which they are found together.
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http://dx.doi.org/10.3389/fpls.2014.00635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231840PMC
December 2014
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