Melanie Pearson

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Melanie Pearson, Ph.D.

Assistant Professor;
Departments of Microbiology (Microbiology ) and Urology (Urology)

Contact Info

Address
550 First Avenue
Room 6102
Medical Science Building
New York, NY 10016

Melanie.Pearson@nyumc.org

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Research Summary

Bacterial pathogenesis during urinary tract infection.

Urinary tract infections (UTI) are a common occurrence. Uncomplicated UTI happen when specialized bacterial pathogens gain access to the bladder of otherwise healthy individuals, and are predominantly caused by a subset of Escherichia coli called uropathogenic E. coli. However, patients with urinary catheters or abnormalities of the urinary tract are highly susceptible to bacterial infections, or complicated UTI. One major contributor to complicated UTI is the Gram-negative species Proteus mirabilis.

P. mirabilis is capable of moving across solid surfaces (including urinary catheters) in large, coordinated blocs of cells, in a specialized process called swarming (figure). P. mirabilis, like many bacteria, also swims through liquids; both swarming and swimming require whip-like appendages called flagella. Once in the urinary tract, P. mirabilis produces urease, which raises urinary pH and leads to stone formation. This bacterium is also able to adhere to host cells lining the urinary tract using protein structures called fimbriae. The P. mirabilis genome potentially encodes 17 unique fimbriae, suggesting that adherence to multiple surfaces contributes to the survival strategy of this species. Many of the fimbrial gene clusters also include a regulatory gene which, when highly expressed, represses flagella (and therefore motility). Thus, P. mirabilis may stick or swim, by controlling which system (fimbriae or flagella) is expressed. The current focus of the Pearson lab is to study these largely uncharacterized fimbriae and fimbria-associated regulators in greater detail.

1. What is the role of fimbriae produced by P. mirabilis? Do all 17 fimbrial operons produce intact fimbriae? When are they expressed, and how many contribute to UTI? What are the targets for these fimbriae? How conserved are these fimbriae in different P. mirabilis isolates? At this time, only 5 of the 17 fimbriae have been studied at any level. One fimbria, the mannose-resistant/Proteus-like (MR/P) fimbria, is predominantly expressed during a mouse model of urinary tract infection, although others contribute to infection or colonization. The host target has not been identified for any of these fimbriae, including MR/P. A range of approaches will be used to study these fimbriae, including PCR and real-time PCR, Western blotting, mutagenesis, and assessment of host response during experimental UTI.

2. What is the role of the fimbria-associated transcriptional regulators? The first gene of this class of regulators to be studied, mrpJ, was found to repress bacterial motility when overexpressed. However, there are 14 additional paralogs of mrpJ in the P. mirabilis genome. When overexpressed, most of them repress motility, but they do not all repress to the same degree and cause distinct abnormalities in swarm behavior. Thus, although MrpJ binds to the promoter of the flagellar master regulator flhDC, this is not necessarily the case for the other genes in this class. There is also some evidence for fimbrial regulation of other fimbriae via MrpJ paralogs. Microarrays, cloning, and mutagenesis will be used to answer these questions.

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search

Characterization of 17 Chaperone-Usher Fimbriae Encoded by Proteus mirabilis Reveals Strong Conservation
Kuan, Lisa; Schaffer, Jessica; Zouzias, Christos D; Pearson, Melanie M
2014 May;:911-922, Journal of medical microbiology
— id: 988132, year: 2014, vol: , page: 911, stat: Journal Article,

Transcriptome of Proteus mirabilis in the murine urinary tract: virulence and nitrogen assimilation gene expression
Pearson, Melanie M; Yep, Alejandra; Smith, Sara N; Mobley, Harry L T
2011 Jul;79(7):2619-2631, Infection & immunity
— id: 136478, year: 2011, vol: 79, page: 2619, stat: Journal Article,

Proteobactin and a yersiniabactin-related siderophore mediate iron acquisition in Proteus mirabilis
Himpsl, Stephanie D; Pearson, Melanie M; Arewang, Carl J; Nusca, Tyler D; Sherman, David H; Mobley, Harry L T
2010 Oct;78(1):138-157, Molecular microbiology
— id: 122429, year: 2010, vol: 78, page: 138, stat: Journal Article,

Transcriptome of swarming Proteus mirabilis
Pearson, Melanie M; Rasko, David A; Smith, Sara N; Mobley, Harry L T
2010 Jun;78(6):2834-2845, Infection & immunity
— id: 122430, year: 2010, vol: 78, page: 2834, stat: Journal Article,

Oxygen-limiting conditions enrich for fimbriate cells of uropathogenic Proteus mirabilis and Escherichia coli
Lane, M Chelsea; Li, Xin; Pearson, Melanie M; Simms, Amy N; Mobley, Harry L T
2009 Mar;191(5):1382-1392, Journal of bacteriology
— id: 122431, year: 2009, vol: 191, page: 1382, stat: Journal Article,

Repression of motility during fimbrial expression: identification of 14 mrpJ gene paralogues in Proteus mirabilis
Pearson, Melanie M; Mobley, Harry L T
2008 Jul;69(2):548-558, Molecular microbiology
— id: 122432, year: 2008, vol: 69, page: 548, stat: Journal Article,

Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility
Pearson, Melanie M; Sebaihia, Mohammed; Churcher, Carol; Quail, Michael A; Seshasayee, Aswin S; Luscombe, Nicholas M; Abdellah, Zahra; Arrosmith, Claire; Atkin, Becky; Chillingworth, Tracey; Hauser, Heidi; Jagels, Kay; Moule, Sharon; Mungall, Karen; Norbertczak, Halina; Rabbinowitsch, Ester; Walker, Danielle; Whithead, Sally; Thomson, Nicholas R; Rather, Philip N; Parkhill, Julian; Mobley, Harry L T
2008 Jun;190(11):4027-4037, Journal of bacteriology
— id: 122433, year: 2008, vol: 190, page: 4027, stat: Journal Article,

Identification of gene products involved in biofilm production by Moraxella catarrhalis ETSU-9 in vitro
Pearson, Melanie M; Hansen, Eric J
2007 Sep;75(9):4316-4325, Infection & immunity
— id: 122436, year: 2007, vol: 75, page: 4316, stat: Journal Article,

The type III secretion system of Proteus mirabilis HI4320 does not contribute to virulence in the mouse model of ascending urinary tract infection
Pearson, Melanie M; Mobley, Harry L T
2007 Oct;56(Pt 10):1277-1283, Journal of medical microbiology
— id: 122434, year: 2007, vol: 56, page: 1277, stat: Journal Article,

A UspA2H-negative variant of Moraxella catarrhalis strain O46E has a deletion in a homopolymeric nucleotide repeat common to uspA2H genes
Wang, Wei; Pearson, Melanie M; Attia, Ahmed S; Blick, Robert J; Hansen, Eric J
2007 Apr;75(4):2035-2045, Infection & immunity
— id: 232592, year: 2007, vol: 75, page: 2035, stat: Journal Article,

Metabolic analysis of Moraxella catarrhalis and the effect of selected in vitro growth conditions on global gene expression
Wang, Wei; Reitzer, Larry; Rasko, David A; Pearson, Melanie M; Blick, Robert J; Laurence, Cassie; Hansen, Eric J
2007 Oct;75(10):4959-4971, Infection & immunity
— id: 122435, year: 2007, vol: 75, page: 4959, stat: Journal Article,

Biofilm formation by Moraxella catarrhalis in vitro: roles of the UspA1 adhesin and the Hag hemagglutinin
Pearson, Melanie M; Laurence, Cassie A; Guinn, Sarah E; Hansen, Eric J
2006 Mar;74(3):1588-1596, Infection & immunity
— id: 122437, year: 2006, vol: 74, page: 1588, stat: Journal Article,

A hag mutant of Moraxella catarrhalis strain O35E is deficient in hemagglutination, autoagglutination, and immunoglobulin D-binding activities
Pearson, Melanie M; Lafontaine, Eric R; Wagner, Nikki J; St Geme, Joseph W 3rd; Hansen, Eric J
2002 Aug;70(8):4523-4533, Infection & immunity
— id: 122438, year: 2002, vol: 70, page: 4523, stat: Journal Article,