Iron-regulated outer membrane proteins of Pasteurella multocida and their role in immunity

Ruffolo, Carmel G; Jost, B. Helen; Adler, Ben

doi:10.1016/s0378-1135(97)00123-5

Cited by 23 publications

(19 citation statements)

References 43 publications

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“…Several in vivo-expressed surface antigens have been identified as potential vaccine candidates (72,538,571). A number of these are iron-regulated Omps expressed during P. multocida infection and have been characterized as potential immunogens in challenge studies (568)(569)(570)(571)(572)(573). For example, the 96-kDa heme acquisition system receptor (HasR) protein is a surfaceexposed Omp conserved among most P. multocida isolates.…”

Section: Vaccinationmentioning

confidence: 99%

Pasteurella multocida: from Zoonosis to Cellular Microbiology

2013

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SUMMARY In a world where most emerging and reemerging infectious diseases are zoonotic in nature and our contacts with both domestic and wild animals abound, there is growing awareness of the potential for human acquisition of animal diseases. Like other Pasteurellaceae , Pasteurella species are highly prevalent among animal populations, where they are often found as part of the normal microbiota of the oral, nasopharyngeal, and upper respiratory tracts. Many Pasteurella species are opportunistic pathogens that can cause endemic disease and are associated increasingly with epizootic outbreaks. Zoonotic transmission to humans usually occurs through animal bites or contact with nasal secretions, with P. multocida being the most prevalent isolate observed in human infections. Here we review recent comparative genomics and molecular pathogenesis studies that have advanced our understanding of the multiple virulence mechanisms employed by Pasteurella species to establish acute and chronic infections. We also summarize efforts being explored to enhance our ability to rapidly and accurately identify and distinguish among clinical isolates and to control pasteurellosis by improved development of new vaccines and treatment regimens.

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Section: Vaccinationmentioning

confidence: 99%

Pasteurella multocida: from Zoonosis to Cellular Microbiology

2013

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“…Successful pathogens must therefore possess an effective response to the limited iron conditions encountered upon entry into a host. Previous studies illustrate the fact that the identities of genes and pathways involved in the acquisition, transport, and utilization of iron in P. multocida are poorly understood (5,6,10,11,13,16). Here we have utilized whole-genome microarray analysis to identify genes with altered expression patterns when P. multocida is grown under iron-limiting conditions.…”

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confidence: 99%

Pasteurella multocida Gene Expression in Response to Iron Limitation

2001

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Pasteurella multocida is the causative agent of a wide range of diseases in avian and mammalian hosts. Gene expression in response to low iron conditions was analyzed in P. multocida using whole-genome microarrays. The analysis shows that the expression of genes involved in energy metabolism and electron transport generally decreased 2.1-to 6-fold while that of genes used for iron binding and transport increased 2.1-to 7.7-fold in P. multocida during the first 2 h of growth under iron-limiting conditions compared with controls. Notably, 27% of the genes with significantly altered expression had no known function, illustrating the limitations of using publicly available databases to identify genes involved in microbial metabolism and pathogenesis. Taken together, the results of our investigations demonstrate the utility of whole-genome microarray analyses for the identification of genes with altered expression profiles during varying growth conditions and provide a framework for the detailed analysis of the molecular mechanisms of iron acquisition and metabolism in P. multocida and other gram-negative bacteria.Pasteurella multocida is a gram-negative, nonmotile, rodshaped, facultative anaerobe that has been isolated from a wide range of mammals and birds throughout the world. This organism is the etiologic agent of a variety of economically significant diseases, including fowl cholera in poultry, hemorrhagic septicemia in cattle and buffalo, atrophic rhinitis in swine, and snuffles in rabbits (9, 12). The global distribution, severity of disease caused, and the wide variety of livestock affected by P. multocida account for considerable economic losses due to this pathogen worldwide (12).Iron is an essential nutrient for most organisms due to its important role in metabolic electron transport chains. Due to the presence of specialized protein carriers such as transferrin and lactoferrin in body fluids, the concentration of free iron normally present in mammalian and avian hosts is not enough to support the in vivo growth of bacteria (1, 2). Successful pathogens must therefore possess an effective response to the limited iron conditions encountered upon entry into a host. Previous studies illustrate the fact that the identities of genes and pathways involved in the acquisition, transport, and utilization of iron in P. multocida are poorly understood (5,6,10,11,13,16). Here we have utilized whole-genome microarray analysis to identify genes with altered expression patterns when P. multocida is grown under iron-limiting conditions. Bacterial growth and RNA isolation. P. multocida PM70 was grown to log phase in a flask of brain-heart infusion (BHI) medium (Becton Dickinson) at 37°C. The culture was split into two 180-ml volumes, briefly centrifuged at 4°C, washed with 1ϫ phosphate-buffered saline (pH 7.0), and centrifuged again. One pellet was resuspended in 180 ml of BHI medium, and the other was resuspended in 180 ml of BHI medium containing the iron chelator 2,2Ј-dipyridyl (200 M) (Sigma, St. Louis, Mo.). The resus...

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“…Previous investigations of P. multocida have identified iron-regulated outer membrane proteins that are produced in response to iron limitation (8,13,18,25,27,30); however, the genes encoding most of these proteins have not been identified. Importantly, Ruffolo and coworkers have shown that P. multocida grown under low-iron conditions can provide cross-protection against subsequent infections (23). More recently, we utilized microarrays to monitor gene expression in P. multocida grown under low-iron conditions formed by the addition of an iron chelator (20).…”

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confidence: 99%

Transcriptional Response of Pasteurella multocida to Defined Iron Sources

et al. 2002

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Pasteurella multocida was grown in iron-free chemically defined medium supplemented with hemoglobin, transferrin, ferritin, and ferric citrate as iron sources. Whole-genome DNA microarrays were used to monitor global gene expression over seven time points after the addition of the defined iron source to the medium. This resulted in a set of data containing over 338,000 gene expression observations. On average, 12% of P. multocida genes were differentially expressed under any single condition. A majority of these genes encoded P. multocida proteins that were involved in either transport and binding or were annotated as hypothetical proteins. Several trends are evident when the data from different iron sources are compared. In general, only two genes (ptsN and sapD) were expressed at elevated levels under all of the conditions tested. The results also show that genes with increased expression in the presence of hemoglobin did not respond to transferrin or ferritin as an iron source. Correspondingly, genes with increased expression in the transferrin and ferritin experiments were expressed at reduced levels when hemoglobin was supplied as the sole iron source. Finally, the data show that genes that were most responsive to the presence of ferric citrate did not follow a trend similar to that of the other iron sources, suggesting that different pathways respond to inorganic or organic sources of iron in P. multocida. Taken together, our results demonstrate that unique subsets of P. multocida genes are expressed in response to different iron sources and that many of these genes have yet to be functionally characterized.

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Iron-regulated outer membrane proteins of Pasteurella multocida and their role in immunity

Cited by 23 publications

References 43 publications

Pasteurella multocida: from Zoonosis to Cellular Microbiology

Pasteurella multocida: from Zoonosis to Cellular Microbiology

Pasteurella multocida Gene Expression in Response to Iron Limitation

Transcriptional Response of Pasteurella multocida to Defined Iron Sources

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