Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum

Patarakul, Kanitha; Lo, Miranda; Adler, Ben

doi:10.1186/1471-2180-10-31

Cited by 67 publications

(73 citation statements)

References 89 publications

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“…Expression of the gene encoding LA0572, predicted to be involved in transport of ferrienterobactin (55), and expression of the gene encoding LA2242, a desferrioxamine receptor homolog, were upregulated (Table 2), similar to what was found in L. biflexa (44). Expression of la2242 is also induced by transition from low to physiological osmolarity conditions (48) and exposure to serum (57).…”

Section: Resultssupporting

confidence: 57%

“…Since heme is likely to be the main source of iron in the host, upregulation of these genes was not surprising, especially given that heme oxygenase is required by L. interrogans for survival in the hamster model of infection (52). Genes encoding LB186 and LB187 were also upregulated in response to an increase in osmolarity (48) and exposure to serum (57), consistent with the importance of these genes for survival in the host.…”

Section: Resultsmentioning

confidence: 52%

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Transcriptional Response ofLeptospira interrogansto Iron Limitation and Characterization of a PerR Homolog

et al. 2010

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Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.

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Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 52%

Transcriptional Response ofLeptospira interrogansto Iron Limitation and Characterization of a PerR Homolog

et al. 2010

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“…We confirmed that clpB is upregulated during heat stress. ClpB was also found to be downregulated in response to serum (29) and under iron-depleted conditions (11).…”

Section: Discussionmentioning

confidence: 92%

Inactivation of clpB in the Pathogen Leptospira interrogans Reduces Virulence and Resistance to Stress Conditions

et al. 2011

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Leptospira interrogans is the causative agent of leptospirosis, which is an emerging zoonotic disease. Resistance to stress conditions is largely uncharacterized for this bacterium. We therefore decided to analyze a clpB mutant that we obtained by random transposon mutagenesis. The mutant did not produce any of the two isoforms of ClpB. The clpB mutant exhibited growth defects at 30°and 37°C and in poor nutrient medium and showed increased susceptibility to oxidative stress, whereas the genetically complemented strain was restored in ClpB expression and in vitro wild-type growth. We also showed that the clpB mutant was attenuated in virulence in an animal model of acute leptospirosis. Our findings demonstrate that ClpB is involved in the general stress response. The chaperone is also necessary, either directly or indirectly, for the virulence of the pathogen L. interrogans.

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“…Quantitation of transcript levels of selected genes. Many Leptospira genetic studies normalize to the endogenous flaB for gene expression analyses because it encodes a highly abundant protein that is synthesized under a variety of conditions (11,(37)(38)(39)(40). However, Leptospira spp.…”

Section: Resultsmentioning

confidence: 99%

Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis

Stewart

Carroll

Olano

et al. 2016

Appl Environ Microbiol

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cThe saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies. Therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of L. biflexa during exponential growth and in stationary phase. Using these data, we identified abundantly produced proteins in each cellular fraction and quantified the transcript levels from a subset of these genes using quantitative reverse transcription-PCR (RT-PCR). These proteins should prove useful as cellular markers and as controls for gene expression studies. We also observed a significant number of L. biflexa membrane-associated proteins with multiple isoforms, each having unique isoelectric focusing points. L. biflexa cell lysates were examined for several posttranslational modifications suggested by the protein patterns. Methylation and acetylation of lysine residues were predominately observed in the proteins of the membrane-associated fraction, while phosphorylation was detected mainly among soluble proteins. These three posttranslational modification systems appear to be conserved between the free-living species L. biflexa and the pathogenic species Leptospira interrogans, suggesting an important physiological advantage despite the varied life cycles of the different species. Members of the genus Leptospira are spirochetal bacteria that share a conserved spiral morphology and motility. Leptospires can be broadly divided into host-associated species (including pathogens and the closely related intermediate species [1]) and free-living saprophytes, and Picardeau et al. proposed that the host-associated species may have evolved from a free-living progenitor (2). Therefore, comparisons between species with different ecological niches may elucidate the mechanisms that allow host-associated species to infect, persist in, and sometimes cause fatal disease in their hosts.Leptospira biflexa, a free-living saprophyte, was discovered over 100 years ago (3) and is often used as a model organism for studies of the genus as a whole (2, 4-6). Although host-associated species, such as Leptospira interrogans, are more intensively studied, they exhibit a low transformation efficiency that approaches the limits of detection. The higher in vitro growth rate and more efficient genetic tools available to manipulate L. biflexa make this organism better suited for laboratory studies. Techniques such as targeted allelic exchange, transposon mutagenesis, conjugative transfer, the use of fluorescent markers, and the use of an inducible promoter system were first developed in L. biflexa before use in L. interrogans (5, 7-9). However, despite its being a model organism, there are significant gaps in our knowledge of L. biflexa. No large-scale microarray data o...

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Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum

Cited by 67 publications

References 89 publications

Transcriptional Response ofLeptospira interrogansto Iron Limitation and Characterization of a PerR Homolog

Transcriptional Response ofLeptospira interrogansto Iron Limitation and Characterization of a PerR Homolog

Inactivation of clpB in the Pathogen Leptospira interrogans Reduces Virulence and Resistance to Stress Conditions

Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis

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