|Miller, William - Bill|
Submitted to: PLoS One
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/13/2008
Publication Date: 4/23/2008
Citation: Quinones, B., Guilhabert, M.R., Miller, W.G., Mandrell, R.E., Lastovica, A.J., Parker, C. 2008. Comparative genomic analysis of clinical strains of Campylobacter jejuni from South Africa. PLoS One. 3(4)e2015_1-e2015_10 Interpretive Summary: Illnesses caused by bacterial foodborne pathogens continue to be a serious health issue worldwide. In laboratory-confirmed cases of infection, Campylobacter jejuni is considered to be one of the most significant bacterial causes of human gastroenteritis (Allos, 2001; Miller & Mandrell, 2005; Snelling, et al., 2005). The majority of C. jejuni infections result in an acute, self-limited gastrointestinal illness. However, in a small number of patients, C. jejuni infection is followed by complications, including septicaemia (Blaser, et al., 1979) and the development of the autoimmune neuropathies, Guillain-Barré (GBS) and Miller-Fisher (MFS) syndromes (Hughes & Cornblath, 2005; Overell & Willison, 2005; Yuki & Koga, 2006). The development of these autoimmune neuropathies after C. jejuni infection is thought to be related to sialylated lipooligosaccharides (LOS) on the cell surface of C. jejuni that exhibit molecular mimicry with gangliosides on peripheral nerves (van Belkum, et al., 2001; Godschalk, et al., 2004, 2007b; Perera, et al., 2007). The range of C. jejuni disease outcomes, extending from acute inflammatory diarrhea to the induction of the autoimmune neuropathies, may be due to genetic differences in the expression of virulence factors in C. jejuni strains in the human hosts. Recent studies have characterized collections of strains from patients with GBS in search of a specific C. jejuni genotype responsible for the development of this neuropathy. C. jejuni strains from GBS cases, with Penner heat-stable (HS) serotypes HS:19 and HS:41, have been shown to be overrepresented in Japan and South Africa, respectively (Kuroki, et al., 1993; Goddard, et al., 1997; Lastovica, et al., 1997; Takahashi, et al., 2005). Further genetic characterization of GBS-associated strains with HS:41 and HS:19 demonstrated that these serotypes represent clonal populations (Wassenaar, et al., 2000; Nachamkin, et al., 2001), suggesting that specific virulence traits relevant to the onset of GBS may be present in strains with these serotypes. Although strains with other common serotypes have been isolated from patients with GBS, the clustering of GBS-associated strains into specific serotypes has not been observed to occur in all worldwide geographical locations (Endtz, et al., 2000; Engberg, et al., 2001). A major contributor to the development of GBS that is distinct from capsular polysaccharide, the Penner serotyping determinant (Karlyshev, et al., 2000), is thought to be C. jejuni LOS. In most patients who develop GBS after C. jejuni enteritis, an induction of their immune response occurs possibly due to anti-C. jejuni LOS antibodies that cross-react with ganglioside epitopes on neural tissues (Yuki & Koga, 2006). In particular, LOS locus classes A, B, and C contain genes involved in the biosynthesis and transfer of sialic acid, an essential component of gangliosides (Gilbert, et al., 2000, 2002), and certain genes in the biosynthesis of these specific LOS classes are proposed to be associated with the induction of the immune response (van Belkum, et al., 2001; Godschalk, et al., 2004, 2007a; Perera, et al., 2007). Further analyses demonstrated that a high frequency of GBS-associated strains all possessed LOS locus class A (Godschalk, et al., 2004, 2007b; Parker, et al., 2005; Koga, et al., 2006) while MFS-associated strains had LOS locus class B (Godschalk, et al., 2004; Koga, et al., 2006). Potentially, a comparative genomic study of a clonal population of C. jejuni strains associated with various disease outcomes could lead to the discovery of those determinants that contribute to the development of GBS. Various sequence-based typing methods, including multilocus sequence typing (MLST) (Dingle, et al., 2001a, 2002; Colles, et al., 2003; Duim, et al., 2003; Manning, et al., 2003; Sails, et al., 2003; Parker, et al., 2007), DNA sequencing of
Technical Abstract: The bacterial foodborne pathogen Campylobacter jejuni is a common cause of acute gastroenteritis and is also associated with the postinfectious neuropathies, Guillain-Barré (GBS) and Miller Fisher (MFS) syndromes. This study described the use of multilocus sequence typing (MLST) and DNA microarrays to examine the genetic content of a collection of South African C. jejuni strains, recovered from patients with GBS, MFS or enteritis. The comparative genomic analysis by MLST and DNA microarrays demonstrated that the South African strains with Penner heat-stable (HS) serotype HS:41 were clearly distinct from the other South African strains. Further analysis of the DNA microarray data demonstrated that the serotype HS:41 strains from South African GBS and enteritis patients are highly similar in gene content. Interestingly, the South African HS:41 strains were distinct in gene content when compared to serotype HS:41 strains from other geographical locations due to the presence of a C. jejuni integrated element (CJIE). Only CJIE1, a Campylobacter Mu-like prophage, was present in the South African HS:41 strains whereas absent in the closely-related HS:41 strains from Mexico. A more distantly-related HS:41 strain from Canada possessed both CJIE1 and CJIE2. These findings demonstrate that CJIEs may contribute to differentiate closely-related C. jejuni strains.