Genetic Analysis of Essential Plasmid Determinants of Pathogenicity in Yersinia pestis

Portnoy, Daniel A.; Blank, Henry; Kingsbury, David T.; Falkow, Stanley

doi:10.1093/infdis/148.2.297

Cited by 91 publications

(76 citation statements)

References 22 publications

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“…The appearance of various non-prototypic plasmids in Y. pestis has been attributed to the presence of insertional elements 2,4 , deletions or recombination of the 110-kb plasmid 5,7 and acquisition of de novo plasmid from elsewhere. 10 Appearance of a dimer of 9.5 kb has been suggested, 4 but has not been examined in detail.…”

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A cryptic 19-kilobase plasmid associated with U.S. isolates of Yersinia pestis: a dimer of the 9.5-kilobase plasmid.

Chu¹,

Dong²,

Zhou³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Yersinia pestis, the etiologic agent of plague, carries three prototypic plasmids with sizes of 110 kb (pFra, pTox), 70 kb (pLcr, pVW, pCad), and 9.5 kb (pPla, pPst). Studies suggest that geographic isolates of Y. pestis may be differentiated by plasmid profiles. Yersinia pestis isolated from the western United States harbor an additional plasmid, estimated to be approximately 19 kb in size. This cryptic plasmid was characterized by restriction endonuclease digestion, amplification and sequencing of the plasminogen activator gene segment, Southern blotting, and visualized by electron microscopy. Results revealed that this cryptic plasmid is a supercoiled DNA plasmid, 18.85 Ϯ 0.59 (mean Ϯ SD) kb in length, and is a dimer of the 9.5-kb plasmid. The genetic reason for the appearance of this form of the 9.5-kb plasmid in Y. pestis from Arizona, California, Colorado, New Mexico, and Texas is under study.Yersinia pestis, the causative agent of plague, carries three prototypical plasmids, 1-3 two of which are unique to Y. pestis, with sizes of 110 kb and 9.5 kb; the third, a 70-kb plasmid, is shared among the pathogenic yersiniae. 2,3 Each of the plasmids contains gene segments that code for diagnostic antigens. The F1 capsular antigen and murine toxin are located on the 110-kb plasmid; thus, this plasmid is referred to as pFra and pTox. The V antigen and Yersinia outer membrane proteins are located on the 70-kb plasmid; this plasmid is under calcium regulation and is referred to as pLcr, pVW, or pCad. The plasminogen activator (pla) and pesticin (pst) gene segments are located on the 9.5-kb plasmid, which is referred to as pPla and as pPst. 4

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A cryptic 19-kilobase plasmid associated with U.S. isolates of Yersinia pestis: a dimer of the 9.5-kilobase plasmid.

Chu¹,

Dong²,

Zhou³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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“…Proteins regulating the expression and secretion of V antigen and Yops are encoded within a ca. 25-kb region of the LCR plasmid termed the Ca2' dependence region (9,13,24,57,78,83).One manifestation of the LCR is the requirement for millimolar calcium or 10 to 20 mM nucleotides, such as ATP, for growth above 34°C (28,84,85). Although growth occurs independently of Ca2+ or ATP at 26°C, a shift in incubation temperature to 37°C in the absence of Ca2+ or ATP results in a cessation of growth within a few generations (28,84).…”

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confidence: 99%

“…Proteins regulating the expression and secretion of V antigen and Yops are encoded within a ca. 25-kb region of the LCR plasmid termed the Ca2' dependence region (9,13,24,57,78,83).…”

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A low-Ca2+ response (LCR) secretion (ysc) locus lies within the lcrB region of the LCR plasmid in Yersinia pestis

1994

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The causative agent of plague, Yersinia pestis, contains a 75-kb plasmid, pCD1, which carries a virulencerelated stimulon called the low-Ca2+ response stimulon (LCRS). LCRS operons are regulated by the environmental signals of temperature and Ca2+. This study characterized a portion of the lkrB region of pCD1, known to contain at least one gene necessary for the regulation of LCRS operons by Ca2+. Ca2" or nucleotides (11,35,78). These genes, which belong to the LCR stimulon (LCRS), encode secreted factors such as V antigen (12, 79) and a set of about 10 virulence proteins called Yops (9,58,76,77,79). Proteins regulating the expression and secretion of V antigen and Yops are encoded within a ca. 25-kb region of the LCR plasmid termed the Ca2' dependence region (9,13,24,57,78,83).One manifestation of the LCR is the requirement for millimolar calcium or 10 to 20 mM nucleotides, such as ATP, for growth above 34°C (28,84,85). Although growth occurs independently of Ca2+ or ATP at 26°C, a shift in incubation temperature to 37°C in the absence of Ca2+ or ATP results in a cessation of growth within a few generations (28,84). This phenomenon is termed growth restriction. Paradoxically, restriction is concurrent with maximal induction of LCRS operons and secretion of LCRS-encoded proteins.V antigen is a soluble protein encoded by the kcrV gene of the lcrGVH-yopBD operon (5,52,59). Although a specific antihost function has not been assigned to V antigen, it is a protective antigen and is believed to be required for full virulence (10,36,73 (65, 66), and sequestration of thrombin (38, 64). V antigen and Yops lack cleavable N-terminal signal sequences and are secreted by an LCRS-encoded mechanism (45). N-terminal sequences have been implicated in directing transport from the cell (43).Previously, two loci within the Ca2" dependence region have been shown to affect both LCRS operon transcription and secretion. LcrD of the lcrDR operon is necessary for maximal induction of LCRS operons and secretion of LCRS-encoded virulence proteins (24,54,55). LcrD has homology to several proteins associated with flagellar biogenesis, invasion of epithelial cells, and plant pathogenesis in taxonomically divergent bacteria (54,78). The LcrD homolog is thought to be a component of a novel secretion system involved in each of these diverse processes.The 13-cistronysc locus is also necessary for the secretion of the V antigen and Yops (27,44). Polar insertion mutants of this region are defective in LCR-specific secretion and show altered regulation of LCRS operon transcription (24,27,44). However, the dominant effects on regulation are the opposite between Y pestis and the enteropathogenic yersiniae, with constitutive downregulation being seen in the former and constitutive induction being seen in the latter (24,27,44). This could arise from different extents of polarity in the respective ysc loci, and sorting out these differences will require analysis of nonpolar mutants in the various ysc genes.Early studies involving the mutagenesis of the Y...

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“…Pathogenic species of the genus Yersinia (Y. enterocolitica, Y. pseudotuberculosis, and Y. pestis) all carry related plasmids that are necessary for virulence (3,17,18,30,44). These plasmids encode a number of proteins, Yops (Yersinia outer membrane proteins) and V antigen, that are induced at 37°C in response to Ca2" starvation, while addition of 2.5 mM Ca2+ suppresses their expression (5,7,12,15,24,33,39).…”

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Genetic analysis of the yopE region of Yersinia spp.: identification of a novel conserved locus, yerA, regulating yopE expression

Försberg

Wolf‐Watz

1990

J Bacteriol

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The yopE gene of Yersinia pseudotuberculosis was recently sequenced, and YopE was identified as an indispensable virulence determinant when tested in a mouse model (A. Forsberg and H. Wolf-Watz, Mol. Microbiol. 2:121-133, 1988). In the study described here, the DNA sequences of the yopE genes of Yersinia pestis EV76 and Yersinia enterocolitica 8081 were determined and compared with that of the Y. pseudotuberculosis gene. Only two codons were found to differ, both leading to amino acid replacements, when the gene from Y. pestis was compared. These two replacements were also present in the gene from Y. enterocolitica; in addition, 18 other codons were found to differ. Thirteen of these substitutions led to amino acid replacements. Downstream of the yopE gene, the plasmid partition locus par was found to be conserved in all three species. In Y. enterocolitica 8081, the sequence homology was interrupted by a putative insertion sequence element inserted between the yopE gene and the par region at a position only 5 base pairs downstream of the yopE stop codon. Upstream of the yopE gene, 620 base pairs were conserved in the three species. This region contained a 130-amino-acid-long open reading frame reading in the opposite direction to the yopE gene and expressed a 14-kilodalton protein in minicells. An insertion mutation in this region constructed in Y. pseudotuberculosis expressed significantly lower amounts of YopE protein in vitro than did the corresponding wild type. The expression level could be restored by transcomplementation. This new locus was designated yerA, for yopE-regulating gene A. The yerA mutant was avirulent when mice were challenged by oral infection.

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Genetic Analysis of Essential Plasmid Determinants of Pathogenicity in Yersinia pestis

Cited by 91 publications

References 22 publications

A cryptic 19-kilobase plasmid associated with U.S. isolates of Yersinia pestis: a dimer of the 9.5-kilobase plasmid.

A cryptic 19-kilobase plasmid associated with U.S. isolates of Yersinia pestis: a dimer of the 9.5-kilobase plasmid.

A low-Ca2+ response (LCR) secretion (ysc) locus lies within the lcrB region of the LCR plasmid in Yersinia pestis

Genetic analysis of the yopE region of Yersinia spp.: identification of a novel conserved locus, yerA, regulating yopE expression

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