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Campylobacter concisus: an emerging pathogen?

Newell, Diane G.

European Journal of Gastroenterology & Hepatology: October 2005 - Volume 17 - Issue 10 - p 1013-1014
Leading Articles

Only about half the cases of intestinal infectious disease have a routinely detectable causative agent diagnosed. Increasingly, evidence indicates that Campylobacter species other than C. jejuni and C. coli are associated with such cases. However, evidence is less clear, from epidemiological studies, for the pathogenic nature of these unusual campylobacters. This is particularly true for organisms like C. concisus and is compounded by poor methods for routine recovery and identification. Moreover, the application of typing methods for C. concisus has indicated a heterogeneous population and there is preliminary evidence to suggest differences in the pathogenic potential of strain types. However, considerable further work is needed with more discriminatory genotyping methods, before accurate assessment of the risk of C. concisus infection to human health can be determined.

MED-VET-NET, Veterinary Laboratories Agency, Addlestone, Surrey, UK

Correspondence to Dr D.G. Newell, Veterinary Laboratories Agency, Addlestone, Surrey KT15 3NB, UK

Tel: +44 (0)1932 357 547; fax: +44 (0)1932 357 268;

e-mail: d.newell@vla.defra.gsi.gov.uk

Accepted 9 June 2005

The Campylobacter genus comprises Gram-negative, nonsacchrolytic bacteria, with microaerobic growth requirements and a low G+C content. There are at least 15 species, all characterized by a spiral, s-shaped or curved rod shaped cells which have a typically rapid motility conferred by means of unsheathed polar flagella. Many of these organisms colonize the mucus overlying the host intestinal tract. The most well known campylobacters are C. jejuni and its close relative C. coli, which are reported to be the most common causes of human acute bacterial enteritis worldwide. However, there are a number of other Campylobacter species, including C. concisus, also with putative roles as enteric agents.

It is well recognized that a significant proportion of intestinal infectious disease has no identified aetiology. In the case–control study undertaken by the Food Standards Agency in England and Wales between 1993 and 1996, 45% of general practitioner cases and 63% of community-based cases of diarrhoea, investigated by the best available culture and/or detection procedures, had no identified causative agent [1]. The use of improved culture methods and PCR-based techniques have suggested that a proportion of these unknown causes may be due to unusual campylobacters [2,3]. At least some of these studies suggest that C. concisus is a significant contributor to disease associated with these unusual campylobacters.

The growth conditions for the various Campylobacter species are fastidious and variable. Differences in temperature, susceptibility to the antimicrobials in selective media and even atmospheric conditions all preclude the development of a single optimal recovery technique. In particular C. concisus is best recovered using filtration onto non-selective medium with 37°C incubation in a hydrogen-rich atmosphere. These conditions are quite different from those generally used in a routine laboratory. In the study by Aabenhus et al. [4] in this issue of European Journal of Gastroenterology & Hepatology, the recovery of C. concisus from 1% of 11 550 stools of patients in a routine laboratory in Denmark bears witness to the sensitivity of the culture methods used and the expertise of the laboratory staff. Interestingly, in this study only 37% of patients had C. jejuni and 8% C. upsaliensis associated disease. This is in contrast to results from the Cape Town laboratory, renowned for its skills in isolating unusual campylobacters, where C. jejuni, C. concisus and C. upsaliensis were roughly of equal prevalence in the diarrhoeic stools of paediatric patients [5]. Other studies provide even more confusing results. For example, in the Intestinal Infectious Disease Study in the United Kingdom [1] 3654 samples of diarrhoeic stools yielded no C. concisus and only four C. upsaliensis infections even using the optimal methodology of filtration. It seems unlikely that such differences are purely geographical or reflect major variations in the population sampled so, clearly, questions about standard culture methodologies will need to be addressed before the prevalence of enteric infection with C. concisus can be determined.

The role of C. concisus as a causative agent of human disease remains arguable. Associations of this organism with periodontal and diarrhoeic diseases are reported but the causative nature of the agent in these clinical presentations has yet to be established. In particular, the comparison of carriage between patients and controls suggests no clear association with enteric disease [6]. One explanation would be the presence of both pathogenic and non-pathogenic subpopulations of C. concisus. Such distinctions are well-recognized in other enteric bacteria, and have even been proposed for C. jejuni. For such organisms, typing methods have been generally useful in demonstrating linkage between strain type and virulence potential. Unfortunately, for C. jejuni, despite a wealth of typing methods, no association has been established, to date, between strain type and virulence. One reason for this is probably the complex and weakly clonal nature of the population structure for this organism.

For C. concisus, only a few investigations have been undertaken on the population structure. Phenotypic methods such as protein profiling using SDS–polyacrylamide gel electrophoresis (SDS–PAGE) clearly demonstrate heterogeneity within this species [4,7]. This heterogeneity defined two clusters, but these groups did not distinguish strains from patients and those from controls. However, SDS–PAGE has indicated a difference in the pathotype of strains from immunocompetent patients and children [8]. Methods like protein profiling are considered to have a relatively poor discriminatory power and for C. jejuni/coli have been largely replaced with genotypic methods. Riboprinting and random amplified polymorphic DNA (RAPD) [7] as well as pulsed field electrophoresis [9] all confirm the heterogeneity within the species, but have failed to identify properties distinguishing strains from patients and controls.

Overall, using improved detection methods, there is evidence that Campylobacter species, other than C. jejuni/coli, are increasingly associated with enteric disease. However, the role of these campylobacters, particularly C. concisus, as emerging pathogens is less clear. The use of alternative genotypic methods, such as MLST, may contribute to this debate. The rapid development of such methods will now be enabled by the recent availability of genome sequences from multiple Campylobacter species [10]. Once the issue of pathogenicity is resolved then the risk to human health from this infection can be determined and the bigger questions, such as sources, will need to be faced. In the meantime we still have to deal effectively with the prevention and control of the major causes of campylobacteriosis, C. jejuni and C. coli.

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References

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Keywords:

campylobacter; enteritis; pathogenicity

© 2005 Lippincott Williams & Wilkins, Inc.