The Genom of Homo sapiens.pdf

EVOLUTION OF HUMAN PATHOGENS 157in survival in the gut by protecting the bacterium from bilesalts (Nesper et al. 2001). Y. pestis produces a rough LPS,lacking an O-antigen as a consequence of these mutationswithin the O-antigen biosynthesis cluster (Skurnik et al.2000). Motility is required for efficient host-cell invasionby Y. enterocolitica (Young et al. 2000) and Y. pseudotuberculosis;Y. pestis strains are uniformly nonmotile, butthe genome sequence showed that they possess two separateclusters of flagellar genes as well as a chemotaxisoperon, which total more than 80 genes (~2% of the totalgenes). Consistent with the failure to observe motility inY. pestis, the flagellar and chemotaxis gene clusters containseveral mutations (Parkhill et al. 2001b; Deng et al.2002). The most important appears to be the frameshift inthe regulator flhD, the effect of which seems to be the silencingof the entire flagellar biosynthesis system.In addition to mutations in the genes required for enteropathogenicity,several of the newly discovered genesthat appear to specify pathogenicity for an insect hosthave also been inactivated. These include the insecticidaltoxin genes tcaB, which contained a frameshift mutation,and tcaC, which possessed an internal deletion. As describedabove, many of these genes are present in the ancestor,Y. pseudotuberculosis, and it may be that the disruptionof these genes is necessary for the new lifestyle ofY. pestis, which persists in the flea gut for relatively longperiods of time.The change in niche accomplished by Y. pestis thus isnot from a mammalian enteric pathogen to a systemicpathogen using an entirely new insect vector for infection.Rather, it appears that the ancestral organism had reachedthe point of maintaining separate fecal–oral infections inboth mammalian and insect hosts. The specific change inniche was to connect the two hosts by a novel transmissionroute, spreading directly from the flea gut to the mammalianhost via a subcutaneous injection. During, or immediatelyfollowing, this change, the organism appears tohave inactivated genes that were unnecessary for, or wouldhinder, this new lifestyle, specifically those involved in interactingwith the mammalian gastrointestinal tract, orthose causing unwanted toxicity in the insect host. Theevolutionary bottleneck associated with this change mayalso have allowed the introduction of mutations into genes,such as those encoding metabolic enzymes, that were neutralor only marginally beneficial to the organism.CONCLUSIONSWe can see that the evolution of these pathogens is opportunistic,taking advantage of new niches as they arise,and losing the ability to occupy the niches previously held.These examples are by no means unique. Preliminary datafrom the sequencing of Bordetella pertussis, a humanspecificpathogen that is the causative agent of whoopingcough, indicates that it is a recently derived degenerateclone of the broad host-range mammalian pathogen Bordetellabronchiseptica. Many of the same processes, includingIS element expansion, pseudogene formation, andgenome rearrangement, have occurred in the derivation ofthis host-specific pathogen. In cases like these, and others,it appears that the rapid changes that have occurred in thehuman population may have created these new niches, andwe can expect bacterial pathogens to rapidly exploit thefurther opportunities afforded them in the future as the humanpopulation continues to expand and diversify.ACKNOWLEDGMENTSWe are very grateful to the sequencing and annotationteams of the Sanger Institute Pathogen Sequencing Unitfor their considerable efforts in generating the data describedin this review.REFERENCESAchtman M., Zurth K., Morelli G., Torrea G., Guiyoule A., andCarniel E. 1999. Yersinia pestis, the cause of plague, is a recentlyemerged clone of Yersinia pseudotuberculosis. Proc.Natl. Acad. Sci. 96: 14043.Andersson D.I. and Hughes D. 1996. Muller’s ratchet decreases fitnessof a DNA-based microbe. Proc. Natl. Acad. Sci. 93: 906.Bach S., de Almeida A., and Carniel E. 2000. The Yersinia highpathogenicityisland is present in different members of thefamily Enterobacteriaceae. FEMS Microbiol. Lett. 183: 289.Bakshi C.S., Singh V.P., Wood M.W., Jones P.W., Wallis T.S.,and Galyov E.E. 2000. Identification of SopE2, a Salmonellasecreted protein which is highly homologous to SopE and involvedin bacterial invasion of epithelial cells. J. Bacteriol.182: 2341.Blackburn M., Golubeva E., Bowen D., and French-ConstantR.H. 1998. A novel insecticidal toxin from Photorhabdus luminescens,toxin complex A (Tca), and its histopathologicaleffects on the midgut of Manduca sexta. Appl. Environ. Microbiol.64: 3036.Blattner F.R., Plunkett G., Bloch C.A., Perna N.T., Burland V.,Riley M., Collado-Vides J., Glasner J.D., Rode C.K., MayhewG.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A.,Rose D.J., Mau B., and Shao Y. 1997. The complete genomesequence of Escherichia coli K-12. Science 277: 1453.Blum G., Ott M., Lischewski A., Ritter A., Imrich H., TschapeH., and Hacker J. 1994. Excision of large DNA regionstermed pathogenicity islands from tRNA- specific loci in thechromosome of an Escherichia coli wild-type pathogen. Infect.Immun. 62: 606.Buchrieser C., Prentice M., and Carniel E. 1998. The 102-kilobaseunstable region of Yersinia pestis comprises a highpathogenicityisland linked to a pigmentation segment whichundergoes internal rearrangement. J. Bacteriol. 180: 2321.Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,Wheeler P.R., Honore N., Garnier T., Churcher C., Harris D.,Mungall K., Basham D., Brown D., Chillingworth T., ConnorR., Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A.,Hamlin N., Holroyd S., Hornsby T., Jagels K., and Lacroix C.,et al. 2001. Massive gene decay in the leprosy bacillus. Nature409: 1007.Cowan C., Jones H.A., Kaya Y.H., Perry R.D., and Straley S.C.2000. Invasion of epithelial cells by Yersinia pestis: Evidencefor a Y. pestis-specific invasin. Infect. Immun. 68: 4523.Darwin A.J. and Miller V.L. 1999. Identification of Yersinia enterocoliticagenes affecting survival in an animal host using signature-taggedtransposon mutagenesis. Mol. Microbiol. 32: 51.Deng W., Burland V., Plunkett G., III, Boutin A., Mayhew G.F.,Liss P., Perna N.T., Rose D.J., Mau B., Zhou S., SchwartzD.C., Fetherston J.D., Lindler L.E., Brubaker R.R., PlanoG.V., Straley S.C., McDonough K.A., Nilles M.L., MatsonJ.S., Blattner F.R., and Perry R.D. 2002. Genome sequence ofYersinia pestis KIM. J. Bacteriol. 184: 4601.Dillard J.P. and Yother J. 1994. Genetic and molecular characterizationof capsular polysaccharide biosynthesis in Streptococcuspneumoniae type 3. Mol. Microbiol. 12: 959.Dillard J.P., Caimano M., Kelly T., and Yother J. 1995. Capsulesand cassettes: Genetic organization of the capsule locus ofStreptococcus pneumoniae. Dev. Biol. Stand. 85: 261.El Tahir Y. and Skurnik M. 2001. YadA, the multifaceted