Nita H Salzman

Medical College of Wisconsin, Milwaukee, Wisconsin, United States

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Publications (58)433.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Enterococcus faecalis is both a common commensal of the human gastrointestinal tract and a leading cause of hospital-acquired infections. Systemic infections with multidrug-resistant enterococci occur subsequent to gastrointestinal colonization. Preventing colonization by multidrug-resistant E. faecalis could therefore be a valuable approach towards limiting infection. However, little is known about the mechanisms E. faecalis uses to colonize and compete for stable gastrointestinal niches. Pheromone-responsive conjugative plasmids encoding bacteriocins are common among enterococcal strains and could modulate niche competition among enterococci or between enterococci and the intestinal microbiota. We developed a model of colonization of the mouse gut with E. faecalis, without disrupting the microbiota, to evaluate the role of the conjugative plasmid pPD1 expressing bacteriocin 21 (ref. 4) in enterococcal colonization. Here we show that E. faecalis harbouring pPD1 replaces indigenous enterococci and outcompetes E. faecalis lacking pPD1. Furthermore, in the intestine, pPD1 is transferred to other E. faecalis strains by conjugation, enhancing their survival. Colonization with an E. faecalis strain carrying a conjugation-defective pPD1 mutant subsequently resulted in clearance of vancomycin-resistant enterococci, without plasmid transfer. Therefore, bacteriocin expression by commensal bacteria can influence niche competition in the gastrointestinal tract, and bacteriocins, delivered by commensals that occupy a precise intestinal bacterial niche, may be an effective therapeutic approach to specifically eliminate intestinal colonization by multidrug-resistant bacteria, without profound disruption of the indigenous microbiota.
    Nature 10/2015; DOI:10.1038/nature15524 · 41.46 Impact Factor

  • Journal of the American College of Surgeons 10/2015; 221(4):S103. DOI:10.1016/j.jamcollsurg.2015.07.239 · 5.12 Impact Factor
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    ABSTRACT: It is clear that IL-10 plays an essential role in maintaining homeostasis in the gut in response to the microbiome. However, it is unknown whether IL-10 also facilitates immune homeostasis at distal sites. To address this question, we asked whether splenic immune populations were altered in IL-10-deficient (Il10(-) (/-)) mice in which differences in animal husbandry history were associated with susceptibility to spontaneous enterocolitis that is microbiome dependent. The susceptible mice exhibited a significant increase in splenic macrophages, neutrophils, and marginal zone (MZ) B cells that was inhibited by IL-10 signaling in myeloid, but not B cells. The increase in macrophages was due to increased proliferation that correlated with a subsequent enhancement in MZ B cell differentiation. Cohousing and antibiotic treatment studies suggested that the alteration in immune homeostasis in the spleen was microbiome dependent. The 16S rRNA sequencing revealed that susceptible mice harbored a different microbiome with a significant increase in the abundance of the bacterial genus Helicobacter. The introduction of Helicobacter hepaticus to the gut of nonsusceptible mice was sufficient to drive macrophage expansion and MZ B cell development. Given that myeloid cells and MZ B cells are part of the first line of defense against blood-borne pathogens, their increase following a breach in the gut epithelial barrier would be protective. Thus, IL-10 is an essential gatekeeper that maintains immune homeostasis at distal sites that can become functionally imbalanced upon the introduction of specific pathogenic bacteria to the intestinal track. Copyright © 2015 by The American Association of Immunologists, Inc.
    The Journal of Immunology 08/2015; 195(7). DOI:10.4049/jimmunol.1500153 · 4.92 Impact Factor
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    ABSTRACT: Otitis media is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear, and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral, and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and asked whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid, and mucus in the middle ear lumens. Further, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1(-/-) mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear. © 2015. Published by The Company of Biologists Ltd.
    Disease Models and Mechanisms 03/2015; 8(5). DOI:10.1242/dmm.019646 · 4.97 Impact Factor
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    ABSTRACT: Establishment of a statistical association between microbiome features and clinical outcomes is of growing interest because of the potential for yielding insights into biological mechanisms and pathogenesis. Extracting microbiome features that are relevant for a disease is challenging and existing variable selection methods are limited due to large number of risk factor variables from microbiome sequence data and their complex biological structure. We propose a tree-based scanning method, Selection of Models for the Analysis of Risk factor Trees (referred to as SMART-scan), for identifying taxonomic groups that are associated with a disease or trait. SMART-scan is a model selection technique that uses a pre-defined taxonomy to organize the large pool of possible predictors into optimized groups, and hierarchically searches and determines variable groups for association test. We investigate the statistical properties of SMART-scan through simulations, in comparison to a regular single-variable analysis and three commonly-used variable selection methods, stepwise regression, least absolute shrinkage and selection operator (LASSO) and classification and regression tree (CART). When there are taxonomic group effects in the data, SMART-scan can significantly increase power by using bacterial taxonomic information to split large numbers of variables into groups. Through an application to microbiome data from a vervet monkey diet experiment, we demonstrate that SMART-scan can identify important phenotype-associated taxonomic features missed by single-variable analysis, stepwise regression, LASSO and CART. Availability: The SMART-scan approach is implemented in R and is available at CONTACT: © The Author (2015). Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Bioinformatics 01/2015; 31(10). DOI:10.1093/bioinformatics/btu855 · 4.98 Impact Factor
  • Edith Porter · Erika V Valore · Rabin Anouseyan · Nita H Salzman ·
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    ABSTRACT: Antimicrobial (poly)peptides (AMPs) are ancient key effector molecules of innate host defense and have been identified in mammals, insects, plants, and even fungi (Nakatsuji and Gallo, J Invest Dermatol, 132: 887-895, 2012). They exhibit a cationic net charge at physiological pH and are rich in hydrophobic amino acids (Dufourc et al., Curr Protein Pept Sci, 13: 620-631, 2012). Their mode of action has been best investigated in bacteria. When assuming secondary structure the cationic and hydrophobic amino acids are sequestered creating a bipartitioned molecule in which the cationic amino acids mediate initial electrostatic interaction with the negatively charged bacterial surface and the hydrophobic amino acids mediate embedding into the bacterial membranes followed by a multitude of effects interfering with bacterial viability (Nicolas, FEBS J, 276: 6483-6496, 2009; Padovan et al., Curr Protein Pept Sci, 11: 210-219, 2010). However, immunomodulatory, antitumor, and other effects have been added to the ever increasing list of AMP functions (Pushpanathan et al., Int J Pept, 2013: 675391, 2013). Several classes of AMPs have been distinguished based on structure, namely anti-parallel beta-sheet, alpha-helical, circular, as well as disulfide bridge connectivity (Bond and Khalid, Protein Pept Lett, 17: 1313-1327, 2010). Many of the AMPs undergo posttranslational modification including further proteolysis. Biochemical analysis at the protein level is of great interest for a wide range of scientists and important when studying host-pathogen interaction, for example Salmonella invasion of the small intestine. Acid-urea polyacrylamide gel electrophoresis (AU-PAGE) followed by Western immunoblotting is an important tool for the identification and quantification of cationic AMPs. The protocol for these procedures outlined here describes, in detail, the necessary steps; including pouring the AU-gels, preparing the test samples, performing the electrophoretic separation and protein transfer to the membrane, and conducting the immunodetection using an alkaline phosphatase/NBT/BCIP system. A standard SDS-PAGE in comparison with AU-PAGE and the corresponding Western immunoblot are depicted in Fig. 1.
    Methods in Molecular Biology 01/2015; 1225:105-15. DOI:10.1007/978-1-4939-1625-2_7 · 1.29 Impact Factor
  • Nita H Salzman ·

    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2014; 113(6):593-598. DOI:10.1016/j.anai.2014.08.020 · 2.60 Impact Factor
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    ABSTRACT: Background There is increasing evidence that intestinal inflammation plays a major role in gastrointestinal symptoms in cystic fibrosis (CF). Fecal calprotectin is a marker that is elevated in several gastrointestinal inflammatory diseases, but little is known about its value in CF. We aimed to look for associations of elevated fecal calprotectin among CF patients and whether its level correlates with the clinical manifestations of CF. Methods A single stool specimen was collected from 62 patients with CF. Fecal calprotectin was measured using the commercially available ELISA kits (PhiCal™ test). Clinical data were collected from patients’ records and CF registry. Results There were no significant differences between CF patients with normal and abnormal fecal calprotectin levels. However, patients who were not receiving inhaled antibiotics had higher fecal calprotectin levels than those who were. Conclusion Elevated fecal calprotectin may not accurately predict intestinal inflammation in CF. However, the fact that it was elevated in both pancreatic sufficient and insufficient groups supports the concept of “cystic fibrosis enteropathy” regardless of the pancreatic status.
    BMC Pediatrics 05/2014; 14(1):133. DOI:10.1186/1471-2431-14-133 · 1.93 Impact Factor
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    ABSTRACT: The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4+ T cells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3γ and Reg3β. RAG1-/- mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4+ T cells. Major histocompatibility class II-/- (MHCII-/-) mice lacking CD4+ T cells also had increased ILCs, IL-22, and AMPs, suggesting that negative regulation by CD4+ T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL-22 is mediated by conventional CD4+ T cells and is T-cell receptor dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII+/- and MHCII-/- littermates. These data define a novel ability of CD4+ T cells to regulate intestinal IL-22-producing ILCs and AMPs.Mucosal Immunology advance online publication, 22 January 2014; doi:10.1038/mi.2013.121.
    Mucosal Immunology 01/2014; 7(5). DOI:10.1038/mi.2013.121 · 7.37 Impact Factor
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    ABSTRACT: BACKGROUND: Increased susceptibility to Crohn's disease (CD) is associated with mutations in several genes that have roles in the functioning of Paneth cells (PCs). PCs produce and secrete antimicrobial peptides and proteins, which are critical for host defense against pathogens and regulation of intestinal homeostasis, notably in regulating the composition of the small intestinal biota. We hypothesize that a significant subset of patients with CD carry susceptibility genes that cause PC dysfunction, resulting in decreased expression of PC antimicrobials, leading to intestinal dysbiosis. We tested this by evaluating a cohort of pediatric patients with CD and non-IBD controls, for genotype, PC gene expression, and microbiota composition.METHODS: We recruited patients <19 years age from Children's hospital of Wisconsin. We obtained clinical data for disease phenotyping. We genotyped subjects for known CD susceptibility gene mutations by Immunochip. Total RNA was isolated from biopsy tissue and analyzed by RTqPCR for levels of PC product gene expression, including defensins HD5 and HD6, lysozyme, sPLA2, and RegIIIgamma. We evaluated differences in PC gene expression among patients with CD and non-inflamed controls. We also characterized the ileal microbiota for bacterial composition and diversity using 16S rRNA gene sequence analysis to determine associations between PC antimicrobial expression and biome composition.RESULTS: We recruited a total of 70 CD patients and 192 non-IBD controls. Control patients skewed younger than disease cohorts. There was male preponderance in CD cohort. Immunochip analysis, subsequently validated by qPCR SNP typing, demonstrated statistically significant correlations between SNP mutations and CD, most notably with the NOD2 insertion mutant (SNP13) (P = 0.0001272). Microbiota analysis showed no significant differences in alpha diversity between control and CD, however there were notable differences in composition. Various sub species of Firmicutes, Actinobacteria and Bacterioidetesare all reduced in CD samples compared to Control. Veillonellaceae (Firmicutes), Alcaligenaceae, Enterobacteriaceae, and Pasteurellaceae (Proteobacteria) are all increased in CD samples. PCA analysis suggested that Lachnospira and Enterobacteria are the main determinants of variance, with a smaller contribution by Prevotella. The relative abundance of bacterial families was significantly different in CD patients compared to controls (Adonis analysis, P < 0.001). The abundance of Lachnospiraceae is consistently higher in controls than CD, while the abundance of Enterobacteriaceae is consistently lower in controls than in CD samples. Ileal samples from CD patients show significantly altered expression of HD6, PSP/REG, and Lysozyme, when compared to controls (Kruskal-Wallis Test).CONCLUSIONS: There are statistically significant correlations between SNP mutations and CD, most notably with the NOD2 insertion mutant (SNP13). The ileal microbiota composition of CD samples differs significantly from control samples. Expression of PC antimicrobial peptides is dysregulated in CD ileal samples compared to controls, with significantly altered expression of human defensin 6, PSP/REG and lysozyme, which may contribute to dysbiosis at the ileal surface. PC morphology and location are abnormal in CD ileal samples compared to controls, which may contribute to abnormalities in mRNA expression.(C) Crohn's & Colitis Foundation of America, Inc.
    Inflammatory Bowel Diseases 12/2013; 19:S119. DOI:10.1097/ · 4.46 Impact Factor
  • Nita H Salzman · Charles L Bevins ·
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    ABSTRACT: The complex community of colonizing microbes inhabiting the mucosal surfaces of mammals is vital to homeostasis and normal physiology in the host. When the composition of this microbiota is unfavorably altered, termed dysbiosis, the host is rendered more susceptible to a variety of chronic diseases. In the mammalian small intestine, specialized secretory epithelial cells, named Paneth cells, produce a variety of secreted antimicrobial peptides that fundamentally influence the composition of the microbiota. Recent investigations have identified numerous genetic and environmental factors that can disrupt normal Paneth cell function, resulting in compromised antimicrobial peptide secretion and consequent dysbiosis. These findings suggest that Paneth cell dysfunction should be considered a common cause of dysbiosis.
    Seminars in Immunology 11/2013; 25(5). DOI:10.1016/j.smim.2013.09.006 · 5.17 Impact Factor
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    ABSTRACT: To study regulatory T (Treg) cell control of chronic autoimmunity in a lymphoreplete host, we created and characterized a new model of autoimmune lung inflammation that targets the medium and small airways. We generated transgenic mice that express a chimeric membrane protein consisting of hen egg lysozyme and a hemoglobin epitope tag under the control of the Clara cell secretory protein promoter, which largely limited transgene expression to the respiratory bronchioles. When Clara cell secretory protein-membrane hen egg lysozyme/hemoglobin transgenic mice were crossed to N3.L2 TCR transgenic mice that recognize the hemoglobin epitope, the bigenic progeny developed dense, pseudo-follicular lymphocytic peribronchiolar infiltrates that resembled the histological pattern of follicular bronchiolitis. Aggregates of activated IFN-γ- and IL-17A-secreting CD4(+) T cells as well as B cells surrounded the airways. Lung pathology was similar in Ifng(-/-) and Il17a(-/-) mice, indicating that either cytokine is sufficient to establish chronic disease. A large number of Ag-specific Treg cells accumulated in the lesions, and Treg cell depletion in the affected mice led to an interstitial spread of the disease that ultimately proved fatal. Thus, Treg cells act to restrain autoimmune responses, resulting in an organized and controlled chronic pathological process rather than a progressive disease.
    The Journal of Immunology 10/2013; 191(11). DOI:10.4049/jimmunol.1301576 · 4.92 Impact Factor
  • B Ey · A Eyking · M Klepak · NH Salzman · J Göthert · M Rünzi · KW Schmid · G Gerken · DK Podolsky · E Cario ·

    Zeitschrift für Gastroenterologie 08/2013; 51(08). DOI:10.1055/s-0033-1352615 · 1.05 Impact Factor
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    ABSTRACT: Variants of the multidrug resistance gene (MDR1/ABCB1) have been associated with increased susceptibility to severe ulcerative colitis (UC). In this study, we investigated the role of TLR/IL-1R signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency. Double- or triple-null mice lacking TLR2, MD-2, MyD88, and MDR1A were generated in the FVB/N background. Deletion of TLR2 in MDR1A deficiency resulted in fulminant pancolitis with early expansion of CD11b(+) myeloid cells and rapid shift toward TH1-dominant immune responses in the lamina propria. Colitis exacerbation in TLR2/MDR1A double-knockout mice required the unaltered commensal microbiota and the LPS coreceptor MD-2. Blockade of IL-1β activity by treatment with IL-1R antagonist (IL-1Ra; Anakinra) inhibited colitis acceleration in TLR2/MDR1A double deficiency; intestinal CD11b(+)Ly6C(+)-derived IL-1β production and inflammation entirely depended on MyD88. TLR2/MDR1A double-knockout CD11b(+) myeloid cells expressed MD-2/TLR4 and hyperresponded to nonpathogenic Escherichia coli or LPS with reactive oxygen species production and caspase-1 activation, leading to excessive cell death and release of proinflammatory IL-1β, consistent with pyroptosis. Inhibition of reactive oxygen species-mediated lysosome degradation suppressed LPS hyperresponsiveness. Finally, active UC in patients carrying the TLR2-R753Q and MDR1-C3435T polymorphisms was associated with increased nuclear expression of caspase-1 protein and cell death in areas of acute inflammation, compared with active UC patients without these variants. In conclusion, we show that the combined defect of two UC susceptibility genes, MDR1A and TLR2, sets the stage for spontaneous and uncontrolled colitis progression through MD-2 and IL-1R signaling via MyD88, and we identify commensally induced pyroptosis as a potential innate immune effector in severe UC pathogenesis.
    The Journal of Immunology 05/2013; 190(11). DOI:10.4049/jimmunol.1201592 · 4.92 Impact Factor

  • Inflammatory Bowel Diseases 12/2012; 18:S107. DOI:10.1097/00054725-201212001-00272 · 4.46 Impact Factor
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    ABSTRACT: "Natural" regulatory T cells (nTregs) that express the transcription factor Foxp3 and produce IL-10 are required for systemic immunological tolerance. "Induced" regulatory T cells (iTregs) are nonredundant and essential for tolerance at mucosal surfaces, yet their mechanisms of suppression and stability are unknown. We investigated the role of iTreg-produced IL-10 and iTreg fate in a treatment model of inflammatory bowel disease. Colitis was induced in Rag1(-/-) mice by the adoptive transfer of naive CD4(+) T cells carrying a nonfunctional Foxp3 allele. At the onset of weight loss, mice were treated with both iTregs and nTregs where one marked subset was selectively IL-10 deficient. Body weight assessment, histological scoring, cytokine analysis, and flow cytometry were used to monitor disease activity. Transcriptional profiling and TCR repertoire analysis were used to track cell fate. When nTregs were present but IL-10 deficient, iTreg-produced IL-10 was necessary and sufficient for the treatment of disease, and vice versa. Invariably, ∼85% of the transferred iTregs lost Foxp3 expression (ex-iTregs) but retained a portion of the iTreg transcriptome, which failed to limit their pathogenic potential upon retransfer. TCR repertoire analysis revealed no clonal relationships between iTregs and ex-iTregs, either within mice or between mice treated with the same cells. These data identify a dynamic IL-10-dependent functional reciprocity between regulatory T cell subsets that maintains mucosal tolerance. The niche supporting stable iTregs is limited and readily saturated, which promotes a large population of ex-iTregs with pathogenic potential during immunotherapy.
    The Journal of Immunology 11/2012; 189(12). DOI:10.4049/jimmunol.1200936 · 4.92 Impact Factor
  • Article: Response.

    The FASEB Journal 11/2012; 26(11):4388-9. DOI:10.1096/fj.12-1103LTR · 5.04 Impact Factor
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    ABSTRACT: P66 is a Borrelia burgdorferi surface protein with β(3) integrin binding and channel forming activities. In this study, the role of P66 in mammalian and tick infection was examined. B. burgdorferiΔp66 strains were not infectious in wild-type, TLR2(-/-) - or MyD88(-/-) -deficient mice. Strains with p66 restored to the chromosome restored near wild-type infectivity, while complementation with p66 on a shuttle vector did not restore infectivity. Δp66 mutants are cleared quickly from the site of inoculation, but analyses of cytokine expression and cellular infiltrates at the site of inoculation did not reveal a specific mechanism of clearance. The defect in these mutants cannot be attributed to nutrient limitation or an inability to adapt to the host environment in vivo as Δp66 bacteria were able to survive as well as wild type in dialysis membrane chambers in the rat peritoneum. Δp66 bacteria were able to survive in ticks through the larva to nymph moult, but were non-infectious in mice when delivered by tick bite. Independent lines of evidence do not support any increased susceptibility of the Δp66 strains to factors in mammalian blood. This study is the first to define a B. burgdorferi adhesin as essential for mammalian, but not tick infection.
    Molecular Microbiology 07/2012; 85(6):1105-1118. DOI:10.1111/j.1365-2958.2012.08160.x · 4.42 Impact Factor
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    ABSTRACT: Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.
    Science 06/2012; 337(6093):477-81. DOI:10.1126/science.1218831 · 33.61 Impact Factor
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    ABSTRACT: Mycobacterium tuberculosis remains a significant global pathogen, causing extensive morbidity and mortality worldwide. This bacterium persists within granulomatous lesions in a poorly characterized, nonreplicating state. The two-component signal transduction systems MprAB and DosRS-DosT (DevRS-Rv2027c) are responsive to conditions likely to be present within granulomatous lesions and mediate aspects of M. tuberculosis persistence in vitro and in vivo. Here, we describe a previously uncharacterized locus, Rv1813c-Rv1812c, that is coregulated by both MprA and DosR. We demonstrate that MprA and DosR bind to adjacent and overlapping sequences within the promoter region of Rv1813c and direct transcription from an initiation site located several hundred base pairs upstream of the Rv1813 translation start site. We further show that Rv1813c and Rv1812c are cotranscribed, and that the genomic organization of this operon is specific to M. tuberculosis and Mycobacterium bovis. Although Rv1813c is not required for survival of M. tuberculosis in vitro, including under conditions in which MprAB and DosRST signaling are activated, an M. tuberculosis ΔRv1813c mutant is attenuated in the low-dose aerosol model of murine tuberculosis, where it exhibits a lower bacterial burden, delayed time to death, and decreased ability to stimulate proinflammatory cytokines interleukin-1β (IL-1β) and IL-12. Interestingly, overcomplementation of these phenotypes is observed in the M. tuberculosis ΔRv1813c mutant expressing both Rv1813c and Rv1812c, but not Rv1813c alone, in trans. Therefore, Rv1813c and Rv1812c may represent general stress-responsive elements that are necessary for aspects of M. tuberculosis virulence and the host immune response to infection.
    Infection and immunity 06/2012; 80(9):3018-33. DOI:10.1128/IAI.00520-12 · 3.73 Impact Factor

Publication Stats

4k Citations
433.66 Total Impact Points


  • 2006-2015
    • Medical College of Wisconsin
      • Department of Pediatrics
      Milwaukee, Wisconsin, United States
  • 2014
    • Children's Hospital of Wisconsin
      Madison, Wisconsin, United States
  • 2011
    • Davis School District
      Davis, California, United States
  • 2008
    • University of Groningen
      • Department of Cell Biology
      Groningen, Groningen, Netherlands
  • 1998
    • The Children's Hospital of Philadelphia
      • Division of Human Genetics and Molecular Biology
      Philadelphia, Pennsylvania, United States