Abstract
‘…an important step forward in our understanding of this group of pathogens and will supply the scientific community, especially young researchers, with a general outlook on the molecular and cellular biology of Yersinia.’
This long-awaited book presents a panoramic overview of three human pathogenic Yersinia species: Yersinia pestis, a deadly agent of plague that killed millions of people in the history of mankind, and two mild enteropathogens, Yersinia pseudotuberculosis and Yersinia entero-colitica. There has recently been a general revival of interest in Y. pestis, which has now been classified as a re-emerging pathogen due to outbreaks in India and Africa, and the existence of a number of active enzootic loci throughout the world (Asia, Africa and the Americas). The high lethality of the plague microbe and the short incubation period by aerosolized application makes plague a conventional tool for terrorists. This can explain the renewed interest in the molecular and cellular biology of the plague agent, as well as closely related enteropathogenic Yersinia.
The content of the book is rather artificially divided into four sections:
| • | Evolution and genomics of Yersinia, which is restricted to Y. pestis | ||||
| • | Cellular biology of Yersinia | ||||
| • | Two sections that deal with molecular biology of chromosome and plasmid-encoded virulence – associated determinants of Yersinia | ||||
The book opens with a comparison of two recently sequenced Y. pestis genomes: biovars Mediaevalis and Orientalis. They are thought to be bound to two plague pandemics: the Black Death and the Modern Plague. However, the author of the second chapter only favors the relationship of the Orientalis isolate to the Modern Plague but not of Mediaevalis to the Black Death. The uncovered genetic changes are a consequence of a recent speciation event that allows the ancestor of Y. pestis to colonize both mammalian and insect hosts. The second chapter tries to fill in the gaps in the history of the young plague microbe, and attempts to build up its natural history, although based on a limited amount of available Y. pestis isolates. The politics of protectionism was always used by certain governments and institutions, and cases of intentional application of biologic agents completely blocked all efforts to exchange scientific materials and information concerning possible bioterroristic agents. Perhaps only a virtual network of standardized data covering naturally existing potential biologic agents nowadays can supply the scientific community with this extremely necessary information.
The next chapter deals with two Y. pestis-specific plasmids, pFra and pPla, which are thought to be responsible for the emergence of Y. pestis as a unique pathogen. However, more recent data on two new pFra plasmids described in strains of Georgian and Chinese origin could add much more to the evolution of this unique replicon. Chapter four tends to build up a picture of Y. pestis interaction with its flea vector and estimate the role of virulence and transmission factors in epidemiology of this blood-borne pathogen. However, it does not reflect the fact that the hms pigmentation locus responsible for blockade of the proventriculus of the flea and biofilm formation is not only present in Y. pestis and its close relative Y. pseudotuberculosis, but also in the more distinct Y. enterocolitica biotype 1B strains not associated with the vector-borne transmission. Thus, this feature has a deeper history in the genus Yersinia.
The next section deals with cellular biology of Yersinia. Acyl-homoserine lactone quorum sensing is highly conserved among pathogenic Yersinia and plays a role in virulence of entero-pathogenic yersinias. However, the role of acylhomoserine lactone sensing in Y. pestis still remains to be determined since no effect was detected on virulence antigens and lipopolysaccharide (LPS) in plague microbe. Also, the action of invasin of enteropathogenic Yersinia is not as simple as initially proposed. At least two disease pathways seem to take place simultaneously in Y. enterocolitica:
| • | Invasin-dependent pathway that results in entry into Peyer’s patches and mesenteric lymph nodes | ||||
| • | Invasin-independent pathway that involves translocation across the intestine via another site and results in seeding of the liver and the spleen | ||||
A bioinformatic approach provides the researchers with a genome-wide overview of established and potential trans-cription factors in Y. pestis. Perhaps it is also the first attempt to explain the different physiologic behavior of Y. pestis and Y. pseudotuberculosis, which are closely related but have a completely different pathogenic life style, not by a simple gene acquisition/loss and genome stirring, but due to differences in gene regulation patterns.
The next chapter points out the application of genome-wide in vivo and in vitro techniques to identify Yersinia genes expressed during the host infection. However, there is an absence of overlap between the spectrum of genes identified by two applied screens: in vivo expression technology and signature-tagged mutagenesis. Perhaps genomic sequences available today will fill this gap. A rather complex picture of Yersinia interaction with the host immune response, both innate and adaptive, is drawn in the next chapter. Still, the authors deal mainly with Y. entero-colitica and less information is been presented for the two other Yersinia pathogens.
A 14,5 kDa Yersinia pseudotuberculosis-derived mitogen (Ypm), a superantigen of Yersinia, turns out to be unique to Y. pseudotuberculosis of Far East origin. Ypm is associated with systematic symptoms most pronounced in Far East pseudotuberculosis, such as erythematous skin rash, cervical lymphadenopathy and the late onset of intestinal nephritis and coronary aneurysms.
The next chapter presents a slice of modern knowledge on Yersinia LPSs. The chemical structures of LPSs have already been determined for a number of yersiniae. However, biologic activities and the role of Y. pestis LPSs in bacterial pathogenesis received little attention and has to be addressed more in future research. The flagella system is not only responsible for migration towards a favorable environment, but also for secretion of virulence factors such as extracellular phospho-lipase YlpA and inhibition of the host control. The presence of two sets of inactivated flagellar genes in Y. pestis probably reflects its adaptation to its new mode of vector-borne dissemination.
The next review presents all of the proven and suspected iron-acquisition systems in Yersinia based on experimental and bioinformatic approaches, as well as the evolution of our understanding of the role of iron-regulated factors in Yersinia pathogenicity. The hierarchy of iron-transport systems required during different stages of the bubonic plague is proposed. The high-pathogenicity island (HPI), regarded as an iron-uptake island, carries genes for the production of the siderophore yersinia-bactin that is absolutely required during the initial stages of infection. The HPI is an active mobile island and is widely disseminated among Enterobacteriaceae, pointing to its fitness role. Another functional pathogenicity island, Yersinia adhesion pathogenicty island (YAPI), codes for Type IV pilus and promotes adherence to the intestinal mucosa. However, its impact on virulence is far from being obvious.
The pYV plasmid is indispensable for Yersinia virulence. It encodes the Yop virulon consisting of a Type III secretion system that allows extracellular yersinias to inject ‘effector’ Yop proteins into the cell cytosol, and thus to inhibit phagocytosis and down regulate the anti-inflammatory response. Although much is performed in this field, we are still far from understanding the actual cell targets of most Type III secretion system effectors while YopM remains a mystery. This review also lacks updated information on the function of promiscous immunogenic V-antigen.
The next chapter presents a possible conversion of an OmpT house-keeping protease into a critical, virulence-associated plasminogen-activator-like protease of Y. pestis. This was achieved by accumulating subtle mutations at critical sites without changing the overall structure of the protein. Pla is a Y. pestis cell-surface protease, which enables bacterial spread from the initial subcutaneous site of a flea bite, but also possesses adhesin and invasin activities. O-antigen prevents plasminogen-activator-like protease function by steric hindrance, which is in agreement with the lack of O-antigen in Y. pestis.
Fraction 1 antigen is a dominant Y. pestis immunogen. Although it stimulates the production of protective antibodies, it is not essential for virulence in rodent models. However, the F1 plus V antigen subunit vaccine is the most promising antiplague vaccine to date. On the other hand, F1 remains a prime target for Y. pestis rapid diagnostic. Application of the F1-negative highly virulent isolate could pose a problem for its diagnostics. Thus, new, suitable antigens should be applied as targets for Y. pestis detection.
The last chapter characterizes the 123-kb pVM82 trans-missive plasmid from the Far Eastern Y. pseudotuberculosis isolate. The review contains a description of clinical manifestations of Far East scarlet fever (FESLF) and points out two differences between FESLF and the typical pseudotuberculosis observed in Europe. The presence of pVM82 correlated with suppression of the rabbit antibody response and suppression of the cellular immune response in a mouse model. However, the real impact of pVM82 plasmid on Yersinia virulence is unclear and needs further investigation, especially in view of the presence of the Ypm superantigen in FESLF isolates.
The main drawback of the book resides in its inability to follow such rapidly developing research fields such as genomics and microbial forensics: most data presented on Yersinia genomes and plasmids are already out of date. The sequenced genomes of Y. pseudotuberculosis O:1, Y. enterocoliticas O:8 and an avirulent Y. pestis 91001 isolate from China are not included in this book. The same is true for two additional sequenced pFra plasmids, isolated from atypical low or avirulent Y. pestis isolates. This material absent from the book could add much more to our understanding of evolution of Yersinia than just the addition of new sequences. Perhaps the slow process of publication in hardback is inadequate for the modern scientific community and other forms of presentation of data have to be established, for example, internet publishing with the possibility of constant updating of information. Also, increasing the scope of the authors and inclusion of alternative points of view might improve the quality of the scientific information presented and add to its timelessness.
Taken together, this book represents an important step forward in our understanding of this group of pathogens and will supply the scientific community and especially young researchers with a general outlook on the molecular and cellular biology of Yersinia.