scholarly journals Evaluation of the Role of Constitutive Isocitrate Lyase Activity in Yersinia pestis Infection of the Flea Vector and Mammalian Host

2004 ◽  
Vol 72 (12) ◽  
pp. 7334-7337 ◽  
Author(s):  
Florent Sebbane ◽  
Clayton O. Jarrett ◽  
Jan R. Linkenhoker ◽  
B. Joseph Hinnebusch

ABSTRACT Yersinia pestis, unlike the closely related Yersinia pseudotuberculosis, constitutively produces isocitrate lyase (ICL). Here we show that the Y. pestis aceA homologue encodes ICL and is required for growth on acetate but not for flea infection or virulence in mice. Thus, deregulation of the glyoxylate pathway does not underlie the recent adaptation of Y. pestis to arthropod-borne transmission.

2003 ◽  
Vol 31 (1) ◽  
pp. 104-107 ◽  
Author(s):  
R.W. Titball ◽  
J. Hill ◽  
D.G. Lawton ◽  
K.A. Brown

Yersinia pestis is the aetiological agent of plague, a disease of humans that has potentially devastating consequences. Evidence indicates that Y. pestis evolved from Yersinia pseudotuberculosis, an enteric pathogen that normally causes a relatively mild disease. Although Y. pestis is considered to be an obligate pathogen, the lifestyle of this organism is surprisingly complex. The bacteria are normally transmitted to humans from a flea vector, and Y. pestis has a number of mechanisms which allow survival in the flea. Initially, the bacteria have an intracellular lifestyle in the mammalian host, surviving in macrophages. Later, the bacteria adopt an extracellular lifestyle. These different interactions with different host cell types are regulated by a number of systems, which are not well characterized. The availability of the genome sequence for this pathogen should now allow a systematic dissection of these regulatory systems.


2011 ◽  
Vol 50 (6) ◽  
pp. 314-321 ◽  
Author(s):  
Joel Bozue ◽  
Sherry Mou ◽  
Krishna L. Moody ◽  
Christopher K. Cote ◽  
Sylvia Trevino ◽  
...  

Microbiology ◽  
2014 ◽  
Vol 160 (2) ◽  
pp. 396-405 ◽  
Author(s):  
Annette M. Uittenbogaard ◽  
Tanya Myers-Morales ◽  
Amanda A. Gorman ◽  
Erin Welsh ◽  
Christine Wulff ◽  
...  

YadB and YadC are putative trimeric autotransporters present only in the plague bacterium Yersinia pestis and its evolutionary predecessor, Yersinia pseudotuberculosis. Previously, yadBC was found to promote invasion of epithelioid cells by Y. pestis grown at 37 °C. In this study, we found that yadBC also promotes uptake of 37 °C-grown Y. pestis by mouse monocyte/macrophage cells. We tested whether yadBC might be required for lethality of the systemic stage of plague in which the bacteria would be pre-adapted to mammalian body temperature before colonizing internal organs and found no requirement for early colonization or growth over 3 days. We tested the hypothesis that YadB and YadC function on ambient temperature-grown Y. pestis in the flea vector or soon after infection of the dermis in bubonic plague. We found that yadBC did not promote uptake by monocyte/macrophage cells if the bacteria were grown at 28 °C, nor was there a role of yadBC in colonization of fleas by Y. pestis grown at 21 °C. However, the presence of yadBC did promote recoverability of the bacteria from infected skin for 28 °C-grown Y. pestis. Furthermore, the gene for the proinflammatory chemokine CXCL1 was upregulated in expression if the infecting Y. pestis lacked yadBC but not if yadBC was present. Also, yadBC was not required for recoverability if the bacteria were grown at 37 °C. These findings imply that thermally induced virulence properties dominate over effects of yadBC during plague but that yadBC has a unique function early after transmission of Y. pestis to skin.


2015 ◽  
Vol 83 (9) ◽  
pp. 3638-3647 ◽  
Author(s):  
Kévin Quintard ◽  
Amélie Dewitte ◽  
Angéline Reboul ◽  
Edwige Madec ◽  
Sébastien Bontemps-Gallo ◽  
...  

TheopgGHoperon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (OPGs) from UDP-glucose, using acyl carrier protein (ACP) as a cofactor. OPGs are required for motility, biofilm formation, and virulence in various bacteria. OpgH also sequesters FtsZ in order to regulate cell size according to nutrient availability.Yersinia pestis(the agent of flea-borne plague) lost theopgGHoperon during its emergence from the enteropathogenYersinia pseudotuberculosis. When expressed in OPG-negative strains ofEscherichia coliandDickeya dadantii,opgGHfromY. pseudotuberculosisrestored OPGs synthesis, motility, and virulence. However,Y. pseudotuberculosisdid not produce OPGs (i) under various growth conditions or (ii) when overexpressing itsopgGHoperon, itsgalUFoperon (governing UDP-glucose), or theopgGHoperon or Acp fromE. coli. A ΔopgGHY. pseudotuberculosisstrain showed normal motility, biofilm formation, resistance to polymyxin and macrophages, and virulence but was smaller. Consistently,Y. pestiswas smaller thanY. pseudotuberculosiswhen cultured at ≥37°C, except when the plague bacillus expressedopgGH.Y. pestisexpressingopgGHgrew normally in serum and within macrophages and was fully virulent in mice, suggesting that small cell size was not advantageous in the mammalian host. Lastly,Y. pestisexpressingopgGHwas able to infectXenopsylla cheopisfleas normally. Our results suggest an evolutionary scenario whereby an ancestralYersiniastrain lost a factor required for OPG biosynthesis but keptopgGH(to regulate cell size). TheopgGHoperon was presumably then lost because OpgH-dependent cell size control became unnecessary.


1970 ◽  
Vol 16 (12) ◽  
pp. 1199-1203 ◽  
Author(s):  
A. Donawa ◽  
W. E. Inniss

Acetate-grown Bacillus megaterium KM possessed high isocitrate lyase and malate synthase activity as compared to glucose-grown cells. Chloramphenicol prevented the increase in isocitrate lyase activity when cells were transferred from glucose to acetate media, indicating that such an increase in activity was probably due to de novo protein synthesis.The affinity of the substrate, isocitrate, was greater for isocitrate dehydrogenase than for isocitrate lyase. Phosphoenolpyruvate was found to inhibit isocitrate lyase non-competitively. The concerted action of glyoxylate and oxaloacetate was capable of inhibiting isocitrate dehydrogenase. The role such factors play in the balancing of the tricarboxylic acid cycle and the glyoxylate pathway in the microorganism is considered.


Microbiology ◽  
2010 ◽  
Vol 156 (4) ◽  
pp. 1201-1210 ◽  
Author(s):  
Jessica M. Hagins ◽  
Jessica A. Scoffield ◽  
Sang-Jin Suh ◽  
Laura Silo-Suh

Pseudomonas aeruginosa is the major aetiological agent of chronic pulmonary infections in patients with cystic fibrosis (CF). The metabolic pathways utilized by P. aeruginosa during these infections, which can persist for decades, are poorly understood. Several lines of evidence suggest that the glyoxylate pathway, which utilizes acetate or fatty acids to replenish intermediates of the tricarboxylic acid cycle, is an important metabolic pathway for P. aeruginosa adapted to the CF lung. Isocitrate lyase (ICL) is one of two major enzymes of the glyoxylate pathway. In a previous study, we determined that P. aeruginosa is dependent upon aceA, which encodes ICL, to cause disease on alfalfa seedlings and in rat lungs. Expression of aceA in PAO1, a P. aeruginosa isolate associated with acute infection, is regulated by carbon sources that utilize the glyoxyate pathway. In contrast, expression of aceA in FRD1, a CF isolate, is constitutively upregulated. Moreover, this deregulation of aceA occurs in other P. aeruginosa isolates associated with chronic infection, suggesting that high ICL activity facilitates adaptation of P. aeruginosa to the CF lung. Complementation of FRD1 with a PAO1 clone bank identified that rpoN negatively regulates aceA. However, the deregulation of aceA in FRD1 was not due to a knockout mutation of rpoN. Regulation of the glyoxylate pathway by RpoN is likely to be indirect, and represents a unique regulatory role for this sigma factor in bacterial metabolism.


2000 ◽  
Vol 68 (6) ◽  
pp. 3419-3425 ◽  
Author(s):  
Petra C. F. Oyston ◽  
Nick Dorrell ◽  
Kerstin Williams ◽  
Shu-Rui Li ◽  
Michael Green ◽  
...  

ABSTRACT The two-component regulatory system PhoPQ has been identified in many bacterial species. However, the role of PhoPQ in regulating virulence gene expression in pathogenic bacteria has been characterized only in Salmonella species. We have identified, cloned, and sequenced PhoP orthologues from Yersinia pestis,Yersinia pseudotuberculosis, and Yersinia enterocolitica. To investigate the role of PhoP in the pathogenicity of Y. pestis, an isogenic phoPmutant was constructed by using a reverse-genetics PCR-based strategy. The protein profiles of the wild-type and phoP mutant strains, grown at either 28 or 37°C, revealed more than 20 differences, indicating that PhoP has pleiotrophic effects on gene expression in Y. pestis. The mutant showed a reduced ability to survive in J774 macrophage cell cultures and under conditions of low pH and oxidative stress in vitro. The mean lethal dose of the phoP mutant in mice was increased 75-fold in comparison with that of the wild-type strain, indicating that the PhoPQ system plays a key role in regulating the virulence of Y. pestis.


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