Black holes and bacterial pathogenicity:: A large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli

被引:322
作者
Maurelli, AT
Fernández, RE
Bloch, CA
Rode, CK
Fasano, A
机构
[1] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA
[2] Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI 48109 USA
[3] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA
关键词
D O I
10.1073/pnas.95.7.3943
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens, For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions, However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximate to 90% of E. coli strains but is uniformly absent in Shigella strains, When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly, The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC, Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella, Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA, Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions, The formation of these "black holes," deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence, Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy, Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.
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页码:3943 / 3948
页数:6
相关论文
共 36 条
  • [1] Ausubel F.A., 1997, CURRENT PROTOCOLS MO, DOI DOI 10.1.4
  • [2] COMPARATIVE GENOME MAPPING WITH MOBILE PHYSICAL MAP LANDMARKS
    BLOCH, CA
    RODE, CK
    OBREQUE, V
    RUSSELL, KY
    [J]. JOURNAL OF BACTERIOLOGY, 1994, 176 (22) : 7121 - 7125
  • [3] Purification of Escherichia coli chromosomal segments without cloning
    Bloch, CA
    Rode, CK
    Obreque, VH
    Mahillon, J
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 223 (01) : 104 - 111
  • [4] BRACHET P, 1995, AM J PHYSIOL, V269, P754
  • [5] POLYNUCLEOTIDE SEQUENCE RELATIONSHIPS AMONG MEMBERS OF ENTEROBACTERIACEAE
    BRENNER, DJ
    FANNING, GR
    JOHNSON, KE
    CITARELLA, RV
    FALKOW, S
    [J]. JOURNAL OF BACTERIOLOGY, 1969, 98 (02) : 637 - +
  • [6] NATURAL POLYAMINES STIMULATE G-PROTEINS
    BUEB, JL
    DASILVA, A
    MOUSLI, M
    LANDRY, Y
    [J]. BIOCHEMICAL JOURNAL, 1992, 282 : 545 - 550
  • [7] TRANSPOSITION AND FUSION OF LAC GENES TO SELECTED PROMOTERS IN ESCHERICHIA-COLI USING BACTERIOPHAGE-LAMBDA AND BACTERIOPHAGE-MU
    CASADABAN, MJ
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1976, 104 (03) : 541 - 555
  • [8] EDWARDS P.R., 1972, IDENTIFICATION ENTER
  • [10] ENTEROTOXIN AND CYTOTOXIN PRODUCTION BY ENTEROINVASIVE ESCHERICHIA-COLI
    FASANO, A
    KAY, BA
    RUSSELL, RG
    MANEVAL, DR
    LEVINE, MM
    [J]. INFECTION AND IMMUNITY, 1990, 58 (11) : 3717 - 3723