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Mycoplasmas – Identifying hosts for a stealth pathogen
The Veterinary Journal The Veterinary Journal 170 (2005) 273–274 www.elsevier.com/locate/tvjl
Guest editorial
Mycoplasmas – Identifying hosts for a stealth pathogen
Mycoplasmas are physically the smallest, and have the smallest genomes, of any free-living organisms. They lack a cell wall and generally have strict nutritional requirements, deriving many of their nutrients from the host. This intimate association with the host, combined with complex growth requirements has traditionally made them difficult to detect and culture in the laboratory. For many years it was believed that this dependence on the host would make mycoplasmas highly host specific. However, in recent years there has been a growing awareness that these ‘‘stealth pathogens’’ could, in some cases at least, be far more widespread and occupy more biological niches than originally thought (Baseman and Tully, 1997). In this issue of The Veterinary Journal, Pitcher and Nicholas (2005) examine the prevalence and host specificity of mycoplasmas. The authors pose the question ‘‘Mycoplasma Host Specificity: Fact or Fiction?’’, but this proves to be a more complex problem than it would initially seem. It is clear that in the past there has been an assumption that mycoplasmas were strongly host specific, when this is probably not always the case. For example, the authors rightly note that several mycoplasma species, such as M. bovis and M. agalactiae amongst others, can pass between sheep, goats and cattle; that M. gatae is found in dogs and cats, and that M. orale and M. salivarum are found both in humans and other primates. This apparent diversity of host range for these species begs the question: exactly what is host specificity? With mycoplasmas, perhaps more so than other bacteria, the answer may not always be obvious. The authors state, ‘‘The host may simply be the species in which the mycoplasma is most frequently detected’’. However, frequency of detection and frequency of occurrence may not necessarily be the same thing. For example, the food-borne pathogen Campylobacter jejuni causes severe diarrhoea, and is most often detected in humans. However, C. jejuni has an optimum growth temperature of 42 °C (the same as a birdÕs body temperature) and survives asymptomatically in more than 50% of all farmed chickens in the US. Few would 1090-0233/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2004.10.015
argue that poultry and not humans are the natural hosts of C. jejuni, but from an epidemiological point of view it is regarded as a human pathogen simply because it is more frequently detected in this host (precisely because we are looking for it). Perhaps the definition of a host as a species in which, in a healthy individual, a mycoplasma can persist indefinitely, whether or not clinical symptoms are observed, would be more accurate? That is, the perfect host can be seen to be the species in which the mycoplasma exists without leaving any evidence of their presence (i.e. no overt disease or immunological response). By this definition of host specificity most parasitic mycoplasmal species would very rarely even be detected. However, this definition highlights the main problem facing the authors of this review; simply not enough is known about the spread, pathogenicity, epidemiology and clinical relevance of species to species spread of mycoplasmas to easily define what a host is, let alone determine Ôhost specificityÕ. What is clear from this paper is that mycoplasmas are probably far more widely spread than had previously been assumed. The authors present evidence of mycoplasmal infections in immunocompromised patients and after xenotransplantation, but this is not necessarily a sign of a wider host range. Most of the observed infections are due to commensal mycoplasmas which are normally present asymptomatically, only resulting in clinical disease due to a malfunction in the hostÕs immune system. The fact that mycoplasmas seem to be so ubiquitous, yet are so rarely detected (unless they are specifically searched for) does highlight one important fact – mycoplasmas are excellent parasites. Although some species produce gross clinical symptoms, as can be the case with contagious bovine pleuropneumonia, others can parasitise hosts but show few or no obvious clinical symptoms. This realisation has led to mycoplasmas being called ‘‘re-emerging’’ pathogens (Baseman and Tully, 1997) and they have been linked to a number of disparate diseases such as Gulf War Syndrome, chronic fatigue syndrome, as a cofactor to AIDS, CrohnÕs
274
Guest editorial / The Veterinary Journal 170 (2005) 273–274
disease and various acquired arthritic conditions, amongst others. The potentially insidious nature of pathogenesis of these organisms, combined with their fastidious growth requirements, further increases the difficulty of determining how host specific mycoplasmas are and how species to species spread affects pathogenicity. Overall, three things are clear from the evidence presented in this thought provoking and timely review. Firstly, mycoplasmas may not be nearly as host and tissue specific as was once thought; secondly, mycoplasmas are more prevalent and occupy more diverse biological niches than was previously assumed and, thirdly, not enough information is available about the distribution and transmission of mycoplasmas for definitive conclusions about the effect of these factors on epidemiology and disease to be drawn. It is only relatively recently that molecular techniques, such as denaturing gradient gel electrophoresis (McAuliffe et al., 2003) have been developed which are sufficiently sensitive and robust to reliably differentiate many closely related mycoplasma species. Hopefully, the accuracy and relative ease of use of this and other similar techniques will allow us to gather greater quantities of more detailed information on the prevalence of
mycoplasmas in a wide range of hosts, whether clinical symptoms are present or not, and allow us to build up a clearer picture of how often species to species transfer of mycoplasmas occurs and what the relevance is to epidemiology and disease. Jason Clark Moredun Research Institute Pentlands Science Park Bush Loan, Penicuik EH26 0PZ, UK E-mail address: [email protected]
References Baseman, J.B., Tully, J.G., 1997. Mycoplasmas: sophisticated, reemerging and burdened by their notoriety. Emerging Infectious Diseases 3, 21–32. McAuliffe, L.M., Ellis, R., Ayling, R.D., Nicholas, R.A.J., 2003. Detection and differentiation of Mycoplasma species by rDNA, PCR and DGGE fingerprinting. Journal of Clinical Microbiology 41, 4844–4847. Pitcher, D.G., Nicholas, R.A.J., 2005. Mycoplasma host specificity: fact or fiction? The Veterinary Journal, doi: 10.1016/j.tvjl.2004.08.11.
Guest editorial
Mycoplasmas – Identifying hosts for a stealth pathogen
Mycoplasmas are physically the smallest, and have the smallest genomes, of any free-living organisms. They lack a cell wall and generally have strict nutritional requirements, deriving many of their nutrients from the host. This intimate association with the host, combined with complex growth requirements has traditionally made them difficult to detect and culture in the laboratory. For many years it was believed that this dependence on the host would make mycoplasmas highly host specific. However, in recent years there has been a growing awareness that these ‘‘stealth pathogens’’ could, in some cases at least, be far more widespread and occupy more biological niches than originally thought (Baseman and Tully, 1997). In this issue of The Veterinary Journal, Pitcher and Nicholas (2005) examine the prevalence and host specificity of mycoplasmas. The authors pose the question ‘‘Mycoplasma Host Specificity: Fact or Fiction?’’, but this proves to be a more complex problem than it would initially seem. It is clear that in the past there has been an assumption that mycoplasmas were strongly host specific, when this is probably not always the case. For example, the authors rightly note that several mycoplasma species, such as M. bovis and M. agalactiae amongst others, can pass between sheep, goats and cattle; that M. gatae is found in dogs and cats, and that M. orale and M. salivarum are found both in humans and other primates. This apparent diversity of host range for these species begs the question: exactly what is host specificity? With mycoplasmas, perhaps more so than other bacteria, the answer may not always be obvious. The authors state, ‘‘The host may simply be the species in which the mycoplasma is most frequently detected’’. However, frequency of detection and frequency of occurrence may not necessarily be the same thing. For example, the food-borne pathogen Campylobacter jejuni causes severe diarrhoea, and is most often detected in humans. However, C. jejuni has an optimum growth temperature of 42 °C (the same as a birdÕs body temperature) and survives asymptomatically in more than 50% of all farmed chickens in the US. Few would 1090-0233/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2004.10.015
argue that poultry and not humans are the natural hosts of C. jejuni, but from an epidemiological point of view it is regarded as a human pathogen simply because it is more frequently detected in this host (precisely because we are looking for it). Perhaps the definition of a host as a species in which, in a healthy individual, a mycoplasma can persist indefinitely, whether or not clinical symptoms are observed, would be more accurate? That is, the perfect host can be seen to be the species in which the mycoplasma exists without leaving any evidence of their presence (i.e. no overt disease or immunological response). By this definition of host specificity most parasitic mycoplasmal species would very rarely even be detected. However, this definition highlights the main problem facing the authors of this review; simply not enough is known about the spread, pathogenicity, epidemiology and clinical relevance of species to species spread of mycoplasmas to easily define what a host is, let alone determine Ôhost specificityÕ. What is clear from this paper is that mycoplasmas are probably far more widely spread than had previously been assumed. The authors present evidence of mycoplasmal infections in immunocompromised patients and after xenotransplantation, but this is not necessarily a sign of a wider host range. Most of the observed infections are due to commensal mycoplasmas which are normally present asymptomatically, only resulting in clinical disease due to a malfunction in the hostÕs immune system. The fact that mycoplasmas seem to be so ubiquitous, yet are so rarely detected (unless they are specifically searched for) does highlight one important fact – mycoplasmas are excellent parasites. Although some species produce gross clinical symptoms, as can be the case with contagious bovine pleuropneumonia, others can parasitise hosts but show few or no obvious clinical symptoms. This realisation has led to mycoplasmas being called ‘‘re-emerging’’ pathogens (Baseman and Tully, 1997) and they have been linked to a number of disparate diseases such as Gulf War Syndrome, chronic fatigue syndrome, as a cofactor to AIDS, CrohnÕs
274
Guest editorial / The Veterinary Journal 170 (2005) 273–274
disease and various acquired arthritic conditions, amongst others. The potentially insidious nature of pathogenesis of these organisms, combined with their fastidious growth requirements, further increases the difficulty of determining how host specific mycoplasmas are and how species to species spread affects pathogenicity. Overall, three things are clear from the evidence presented in this thought provoking and timely review. Firstly, mycoplasmas may not be nearly as host and tissue specific as was once thought; secondly, mycoplasmas are more prevalent and occupy more diverse biological niches than was previously assumed and, thirdly, not enough information is available about the distribution and transmission of mycoplasmas for definitive conclusions about the effect of these factors on epidemiology and disease to be drawn. It is only relatively recently that molecular techniques, such as denaturing gradient gel electrophoresis (McAuliffe et al., 2003) have been developed which are sufficiently sensitive and robust to reliably differentiate many closely related mycoplasma species. Hopefully, the accuracy and relative ease of use of this and other similar techniques will allow us to gather greater quantities of more detailed information on the prevalence of
mycoplasmas in a wide range of hosts, whether clinical symptoms are present or not, and allow us to build up a clearer picture of how often species to species transfer of mycoplasmas occurs and what the relevance is to epidemiology and disease. Jason Clark Moredun Research Institute Pentlands Science Park Bush Loan, Penicuik EH26 0PZ, UK E-mail address: [email protected]
References Baseman, J.B., Tully, J.G., 1997. Mycoplasmas: sophisticated, reemerging and burdened by their notoriety. Emerging Infectious Diseases 3, 21–32. McAuliffe, L.M., Ellis, R., Ayling, R.D., Nicholas, R.A.J., 2003. Detection and differentiation of Mycoplasma species by rDNA, PCR and DGGE fingerprinting. Journal of Clinical Microbiology 41, 4844–4847. Pitcher, D.G., Nicholas, R.A.J., 2005. Mycoplasma host specificity: fact or fiction? The Veterinary Journal, doi: 10.1016/j.tvjl.2004.08.11.