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Standing genetic variation in contingency loci drives the rapid adaptation of Campylobacter jejuni to a novel host.

Jerome JP, Bell JA, Plovanich-Jones AE, Barrick JE, Brown CT, Mansfield LS - PLoS ONE (2011)

Bottom Line: Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci.These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions.Several loci with open reading frame changes also had altered transcript abundance.

View Article: PubMed Central - PubMed

Affiliation: Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, United States of America.

ABSTRACT
The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10(-/-) mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64 Mb genome to 200-500 X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.

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In vitro phenotypes of mouse-adapted C. jejuni.(A) Soft agar plates allow motile C. jejuni to spread from the center of inoculation. The ability to spread is based on flagellar motility. The top right spot is the wild-type variant and shown going clockwise are mouse-adapted variants passaged one, two, or three times through mice. All have spread an equal amount after 48 hours. (B) A higher final OD600 for the mouse-adapted variant indicates a decreased ability to autoagglutinate. Standard error bars are shown.
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pone-0016399-g003: In vitro phenotypes of mouse-adapted C. jejuni.(A) Soft agar plates allow motile C. jejuni to spread from the center of inoculation. The ability to spread is based on flagellar motility. The top right spot is the wild-type variant and shown going clockwise are mouse-adapted variants passaged one, two, or three times through mice. All have spread an equal amount after 48 hours. (B) A higher final OD600 for the mouse-adapted variant indicates a decreased ability to autoagglutinate. Standard error bars are shown.

Mentions: It has been reported that non-motile and non-autoagglutinating C. jejuni mutants are attenuated [37], and we hypothesized that these phenotypes may have changed during passage in mice. Spreading on soft agar plates was equal in the wild-type and mouse-adapted variants, indicating that both C. jejuni were fully motile (Figure 3a). Also, darting motility was seen in both variants when observed in wet mounts by bright field microscopy. However, the ability to autoagglutinate was slightly decreased in mouse-adapted cells (Figure 3b). Although the change was small, it was statistically significant and reproducible.


Standing genetic variation in contingency loci drives the rapid adaptation of Campylobacter jejuni to a novel host.

Jerome JP, Bell JA, Plovanich-Jones AE, Barrick JE, Brown CT, Mansfield LS - PLoS ONE (2011)

In vitro phenotypes of mouse-adapted C. jejuni.(A) Soft agar plates allow motile C. jejuni to spread from the center of inoculation. The ability to spread is based on flagellar motility. The top right spot is the wild-type variant and shown going clockwise are mouse-adapted variants passaged one, two, or three times through mice. All have spread an equal amount after 48 hours. (B) A higher final OD600 for the mouse-adapted variant indicates a decreased ability to autoagglutinate. Standard error bars are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3025981&req=5

pone-0016399-g003: In vitro phenotypes of mouse-adapted C. jejuni.(A) Soft agar plates allow motile C. jejuni to spread from the center of inoculation. The ability to spread is based on flagellar motility. The top right spot is the wild-type variant and shown going clockwise are mouse-adapted variants passaged one, two, or three times through mice. All have spread an equal amount after 48 hours. (B) A higher final OD600 for the mouse-adapted variant indicates a decreased ability to autoagglutinate. Standard error bars are shown.
Mentions: It has been reported that non-motile and non-autoagglutinating C. jejuni mutants are attenuated [37], and we hypothesized that these phenotypes may have changed during passage in mice. Spreading on soft agar plates was equal in the wild-type and mouse-adapted variants, indicating that both C. jejuni were fully motile (Figure 3a). Also, darting motility was seen in both variants when observed in wet mounts by bright field microscopy. However, the ability to autoagglutinate was slightly decreased in mouse-adapted cells (Figure 3b). Although the change was small, it was statistically significant and reproducible.

Bottom Line: Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci.These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions.Several loci with open reading frame changes also had altered transcript abundance.

View Article: PubMed Central - PubMed

Affiliation: Comparative Enteric Diseases Laboratory, Michigan State University, East Lansing, Michigan, United States of America.

ABSTRACT
The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10(-/-) mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64 Mb genome to 200-500 X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.

Show MeSH
Related in: MedlinePlus