Olfactory fMRI in Patients with Parkinson's Disease

Hyposmia is one of the early signs in idiopathic Parkinson's disease (PD). Olfactory stimuli were applied during fMRI scanning to show disease-related modulation of central nervous system structures and to advance our understanding of olfactory dysfunction in PD patients. All participants received either unpleasant stimuli that smelled like rotten eggs or pleasant ones that smelled like roses. Using a block design at a 1.5 T scanner we investigated a total of 8 PD patients (mean age 60 ± 10.9 years) and 13 age matched controls (mean age 58 ± 9.6 years). PD duration ranged from 1 to 9 years (mean 6.63 years); patients had an average “Unified Parkinson's Disease Rating Scale III” score of 23.25 (range, 6–46). Olfactory function was established using the “Sniffin’ Sticks” test battery. Patients tended to rate the stimuli presented during fMRI scans as less intense, but also as more pleasant than controls. fMRI results revealed differences between PD patients and controls which depended on the type of stimulation. While both pleasant and unpleasant stimulation was associated with lower activation in the amygdalo–hippocampal complex in patients compared to controls, increased activity in response to pleasant stimuli was observed in the striatum and the left inferior frontal gyrus. In contrast, unpleasant stimulation led to hypoactivation of the ventral striatum in patients (but not in controls) and did not enhance left inferior frontal activity. These results may partly reflect differences between PD patients and healthy controls in the processing of primary dimensions of odors, intensity, and valence

Granulomatous Inflammation in ANCA-Associated Vasculitis

ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites

Activation of Microglial Poly(ADP-Ribose)-Polymerase-1 by Cholesterol Breakdown Products during Neuroinflammation: a Link between Demyelination and Neuronal Damage

Multiple sclerosis (MS) is a chronic demyelinating disease in which it has only recently been suggested that damage to neuronal structures plays a key role. Here, we uncovered a link between the release of lipid breakdown products, found in the brain and cerebrospinal fluid (CSF) of MS patients as well as in experimental autoimmune encephalomyelitis, and neuronal damage mediated by microglial activation. The concentrations of the breakdown product 7-ketocholesterol detected in the CSF of MS patients were capable of inducing neuronal damage via the activation and migration of microglial cells in living brain tissue. 7-ketocholesterol rapidly entered the nucleus and activated poly(ADP-ribose)-polymerase (PARP)-1, followed by the expression of migration-regulating integrins CD11a and intercellular adhesion molecule 1. These findings reveal a novel mechanism linking demyelination and progressive neuronal damage, which might represent an underlying insidious process driving disease beyond a primary white matter phenomenon and rendering the microglial PARP-1 a possible antiinflammatory therapeutic target

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Predictors of dropout in the German disease management program for type 2 diabetes

Background: To improve and assess the effectiveness of disease management programs (DMPs), it is critical to understand how many people drop out of disease management programs and why. Methods: We used routine data provided by a statutory health insurance fund from the regions North Rhine, North Wurttemberg and Hesse. As part of the German DMP for type 2 diabetes, the insurance fund received regular documentation of all members participating in the program. We followed 10,989 patients who enrolled in the DMP between July 2004 and December 2005 until the end of 2007 to study how many patients dropped out of the program. Dropout was defined based on the discontinuation of program documentation on a particular patient, excluding situations in which the patient died or left the insurance fund. Predictors of dropout, assessed at the time of program enrolment, were explored using logistic regression analysis. Results: 5.5% of the patients dropped out of the disease management program within the observation period. Predictors of dropout at the time of enrolment were: region; retirement status; the number of secondary diseases; presence of a disabling secondary disease; doctors recommendations to stop smoking or to seek nutritional counselling; and the completion and outcome of the routine foot and eye exams. Different trends of dropout were observed among retired and employed patients: retired patients of old age, who possibly drop out of the program due to other health care priorities and employed people of younger age who have not yet developed many secondary diseases, but were recommended to change their lifestyle. Conclusions: Overall, dropout rates for the German disease management programs for type 2 diabetes were low compared to other studies. Factors assessed at the time of program enrolment were predictive of later dropout and should be further studied to provide information for future program improvements

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Comparative genome analysis and genome-guided physiological analysis of Roseobacter litoralis

<p>Abstract</p> <p>Background</p> <p><it>Roseobacter litoralis </it>OCh149, the type species of the genus, and <it>Roseobacter denitrificans </it>OCh114 were the first described organisms of the <it>Roseobacter </it>clade, an ecologically important group of marine bacteria. Both species were isolated from seaweed and are able to perform aerobic anoxygenic photosynthesis.</p> <p>Results</p> <p>The genome of <it>R. litoralis </it>OCh149 contains one circular chromosome of 4,505,211 bp and three plasmids of 93,578 bp (pRLO149_94), 83,129 bp (pRLO149_83) and 63,532 bp (pRLO149_63). Of the 4537 genes predicted for <it>R. litoralis</it>, 1122 (24.7%) are not present in the genome of <it>R. denitrificans</it>. Many of the unique genes of <it>R. litoralis </it>are located in genomic islands and on plasmids. On pRLO149_83 several potential heavy metal resistance genes are encoded which are not present in the genome of <it>R. denitrificans</it>. The comparison of the heavy metal tolerance of the two organisms showed an increased zinc tolerance of <it>R. litoralis</it>. In contrast to <it>R. denitrificans</it>, the photosynthesis genes of <it>R. litoralis </it>are plasmid encoded. The activity of the photosynthetic apparatus was confirmed by respiration rate measurements, indicating a growth-phase dependent response to light. Comparative genomics with other members of the <it>Roseobacter </it>clade revealed several genomic regions that were only conserved in the two <it>Roseobacter </it>species. One of those regions encodes a variety of genes that might play a role in host association of the organisms. The catabolism of different carbon and nitrogen sources was predicted from the genome and combined with experimental data. In several cases, e.g. the degradation of some algal osmolytes and sugars, the genome-derived predictions of the metabolic pathways in <it>R. litoralis </it>differed from the phenotype.</p> <p>Conclusions</p> <p>The genomic differences between the two <it>Roseobacter </it>species are mainly due to lateral gene transfer and genomic rearrangements. Plasmid pRLO149_83 contains predominantly recently acquired genetic material whereas pRLO149_94 was probably translocated from the chromosome. Plasmid pRLO149_63 and one plasmid of <it>R. denitrifcans </it>(pTB2) seem to have a common ancestor and are important for cell envelope biosynthesis. Several new mechanisms of substrate degradation were indicated from the combination of experimental and genomic data. The photosynthetic activity of <it>R. litoralis </it>is probably regulated by nutrient availability.</p

The Role of Sedentary Behavior in Cardio-Preventive Research

Background: Sedentary behavior (SB) is a modifiable behavior with increasing prevalence worldwide. There is emerging evidence that time spend in SB and the manner in which SB is accumulated over time is associated with cardiovascular and cardiometabolic health. The requirement for SB data to be accurately measured is minimization, or at least accurate quantification of human-related sources of measurement errors such as accelerometer measurement reactivity (AMR). The present thesis was to examine SB and their associations with cardiovascular and cardiometabolic health, and to focus on challenges related to the assessment of SB. The first aim of the thesis was to identify patterns of SB describing how individuals accumulate their time spend in SB day-by-day over one week, and to examine how these patterns are associated with cardiorespiratory fitness as a marker for cardiovascular health (paper 1). The second aim of the thesis was to examine the multiple types of SB, and how this is associated with a clustered cardiometabolic risk score (CMRS; paper 2). The third aim of the thesis was to examine AMR and the reproducibility in SB and physical activity (PA) in two measurement periods, and to quantify AMR as a confounder for the estimation of the reproducibility of SB and PA data (paper 3). Methods: The three papers were based on data of two different studies. For study 1, 1165 individuals aged 40 to 75 years were recruited in three different settings. Among these, 582 participated in a cardiovascular risk factor screening program including cardiopulmonary exercise testing. For the analyses of paper 1, 170 participants were eligible, agreed to wear an accelerometer, fulfilled the wearing regime, and completed the study period by wearing the accelerometer for seven consecutive days. Patterns in accelerometer data were classified based on time spent in SB per day applying growth mixture modeling. Model‐implied class‐specific peak oxygen uptake (VO2peak) means were compared using adjusted equality test of means (paper 1). The underlying study of paper 2 and 3 were based on data of a pilot study aiming to investigate the feasibility of a brief tailored letter intervention to increase PA and to reduce SB during leisure time. Among the individuals who agreed to be contacted again in study 1, a random sample of those aged between 40 and 65 years was drawn. Of those, 175 attended in a cardiovascular examination program. Assessment included giving blood sample, standardized measurement of blood pressure, waist circumference, body weight, and height at baseline, and after twelve months. Further, they agreed to complete a paper-pencil questionnaire on SB (Last 7-d Sedentary Behavior Questionnaire, SIT-Q-7d) and PA (International Physical Activity Questionnaire, IPAQ), and to receive seven-day accelerometery at baseline, and after 12 months. In addition, self-administered assessments were conducted at months one, three, four, and six after baseline. Only individuals of a random subsample (= intervention group) received up to three letters tailored to their self-reported SB and PA at months one, three, and four. For paper 2, associations between SBs and a clustered cardiometabolic risk score (CMRS) were analyzed using linear as well as quantile regression. To account for missing values at baseline, multiple imputations using chained equations were performed resulting in a total sample of 173 participants. Paper 3 comprised data of 136 individuals who participated at the baseline and twelve months assessments, and fulfilled the wearing regime. AMR was examined using latent growth modeling in each measurement period. Intraclass correlations (ICC) were calculated to examine the reproducibility of SB and PA data using two-level mixed-effects linear regression analyses. Results: Results of paper 1 revealed four patterns of SB: 'High, stable', 'Low, increase', 'Low, decrease', and 'High, decrease'. Persons in the class 'High, stable' had significantly lower VO2peak values (M = 25.0 mL/kg/min, SD = 0.6) compared to persons in the class 'Low, increase' (M = 30.5 mL/kg/min, SD = 3.6; p = 0.001), in the class 'Low, decrease' (M = 30.1 mL/kg/min, SD = 5.0; p = 0.009), and in the class High, decrease' (M = 29.6 mL/kg/min, SD = 5.9; p = 0.032), respectively. No differences among the other classes were found. In paper 2, results revealed that the only factor positively associated with a CMRS in all regression models was watching television. Depending on the regression analysis approach used, other leisure-time SBs showed inconsistent (using a computer), or no associations (reading and socializing) with a CMRS. In paper 3, results revealed that time spent in SB increased (baseline: b = 2.3 min/d; after 12 months: b = 3.8 min/d), and time spent in light PA decreased (b = 2.0 min/day; b = 3.3 min/d). However, moderate-to-vigorous PA remained unchanged. Accelerometer wear time was reduced (b = 4.6 min/d) only at baseline. The ICC coefficients ranged from 0.42 (95% CI = 0.29 - 0.57) for accelerometer wear time to 0.70 (95% CI = 0.61 - 0.78) for moderate-to-vigorous PA. None of the regression models identified a reactivity indicator as a confounder for the reproducibility of SB and PA data. Conclusions: The present thesis highlights SB in the field of cardiovascular and cardiometabolic research that have implications for future research. Individuals sit for different purposes and durations in multiple life domains, and the time spent in SB is accumulated in different patterns over time. Therefore, research should consider the fact that SB is embedded in an individual's daily life routine, hence might have differential effects on cardiovascular and cardiometabolic health. Further, methodological aspects have to be considered when dealing with SB. In order to detect how SB is 'independently' associated to an individual's health, an accurate measurement of SB is fundamental. Therefore, human-related sources of bias such as AMR should be taken into account when either planning studies or when interpreting data drawn from analysis of SB data.Hintergrund: Sitzen ist ein modifizierbares Verhalten, das weltweit immer häufiger auftritt. Forschungsergebnisse deuten darauf hin, dass die Zeit, die man im Sitzen verbringt, und die Art und Weise, wie sich die Sitzzeiten zusammensetzen, mit der kardiovaskulären und kardiometabolischen Gesundheit einer Person zusammenhängen. Die grundlegende Voraussetzung für eine genaue Messung des Sitzens ist jedoch, dass Ursachen von Messfehlern, wie beispielsweise die Reaktivität beim Tragen eines Akzelerometers, minimiert oder zumindest hinreichend genau quantifiziert werden können. In der vorliegenden Arbeit wurden Zusammenhänge zwischen dem Sitzen und der kardiovaskulären und kardiometabolischen Gesundheit untersucht und Aspekte hervorgehoben, die genaue Messungen von Sitzverhalten beeinflussen können. Im ersten Artikel wird der Frage nachgegangen, wie viele und welche Sitzmuster bei Personen über eine Woche identifiziert werden können und ob diese mit der kardiorespiratorischen Fitness, als wesentlicher Parameter für die kardiovaskuläre Gesundheit, assoziiert sind. Im zweiten Artikel wurde die Frage untersucht, in welchen verschiedenen Sitzverhaltensweisen Personen ihre Zeit verbringen und ob dies mit einem kontinuierlichen Risikoscore der kardiometabolischen Gesundheit (CMRS) zusammenhängt. Der dritte Artikel adressiert die Frage, ob das Tragen eines Akzelerometers reaktives Verhalten hervorruft und in welchem Ausmaß sich Reaktivität über wiederholte Messungen zeigt. Zudem wurde untersucht, in welchem Ausmaß Sitzverhalten und körperliche Bewegung reproduzierbar sind und ob Reaktivität als konfundierender Faktor für die Reproduzierbarkeit von Sitz- und Bewegungsdaten quantifizierbar ist. Methode: Die drei Artikel basieren auf Daten aus zwei Studien. Für Studie 1 wurden 1165 Personen im Alter von 40 bis 75 Jahren in drei Settings rekrutiert, von denen 582 an einem Programm zum Screening von kardiovaskulären Risikofaktoren, ein kardiopulmonaler Belastungstest eingeschlossen, teilnahmen. Von diesen waren 170 eligible Teilnehmer, das heißt sie trugen an sieben aufeinander folgenden Tagen ein Akzelerometer und erfüllten die Tragekriterien. Zur Modellierung der Veränderungen über den Tragezeitraum hinsichtlich der im Sitzen verbrachten Zeit und zur Identifizierung von dahinterliegenden Sitzmustern wurden latente Wachstumskurvenmodelle berechnet. Modell-implizierte klassenspezifische Mittelwerte für die maximale Sauerstoffaufnahme (VO2peak) wurden mit Hilfe von Chi-Quadrat-Tests verglichen (Artikel 1). Die Ergebnisse des zweiten und dritten Artikels basierten auf Daten einer Machbarkeitsstudie für eine computergestützte Kurzintervention mit dem Ziel eine Steigerung der körperlichen Aktivität und eine Reduktion von Sitzzeiten während der Freizeit zu erreichen. Aus einer Zufallsstichprobe von kontaktbereiten Personen im Alter zwischen 40 und 65 Jahren aus Studie 1, nahmen 175 Personen erneut an einem kardiovaskulären Untersuchungsprogramm teil. Dieses umfasste eine Blutprobenentnahme sowie eine standardisierte Messung des Blutdrucks, des Taillenumfangs, des Körpergewichts und der Körpergröße zu Baseline und nach 12 Monaten. Zu beiden Zeitpunkten wurden von den Teilnehmern ein Fragebogen zum Sitzverhalten (Last 7-d Sedentary Behavior Questionnaire, SIT-Q-7d) und zur körperlichen Bewegung (International Physical Activity Questionnaire, IPAQ) ausgefüllt und ein Akzelerometer an sieben aufeinander folgenden Tagen getragen. Die Fragebögen wurden zusätzlich noch nach dem ersten, dritten, vierten und sechsten Monat nach Baseline ausgefüllt. Eine per Zufall ausgewählte Gruppe von Teilnehmern erhielt im ersten, dritten und vierten Monat bis zu drei automatisiert generierte schriftliche Feedbackbriefe zu Sitzverhalten und körperlicher Bewegung. Für den zweiten Artikel wurden Assoziationen zwischen verschiedenen Sitzverhaltensweisen in der Freizeit und dem CMRS mit Hilfe einer linearen Regression sowie Quantilregression analysiert. Nach multipler Imputation für fehlende Baselinewerte, ergab sich eine Gesamtstichprobe von 173 Teilnehmern führte. Der dritte Artikel umfasst Daten von insgesamt 136 Personen, die zu Baseline und nach 12 Monaten an der Studie teilnahmen und die Tragekriterien für das Akzelerometer erfüllten. Zur Modellierung der Veränderungen über den Tragezeitraum hinsichtlich der im Sitzen verbrachten Zeit sowie des Zeitumfangs leichter und moderat bis anstrengender körperlicher Bewegung wurden latente Wachstumskurvenmodelle berechnet. Basierend auf Mehrebenenanalysen mit linearen gemischten Modellen wurden Intraclass-Korrelationen (ICC) berechnet, um die Reproduzierbarkeit der Sitz- und Bewegungsdaten einschätzen zu können. Ergebnisse: Die Ergebnisse des ersten Artikels zeigten vier Sitzmuster: "Hoch, stabil", "Niedrig, erhöht", "Niedrig, verringert" und "Hoch, verringert". Personen der Klasse "Hoch, stabil" hatten signifikant niedrigere VO2peak-Werte (M = 25.0 ml/ kg/ min, SD = 0.6) im Vergleich zu Personen der Klasse "Niedrig, erhöht" (M = 30.5 ml/ kg/ min, SD = 3.6; p = 0.001), der Klasse "Niedrig, verringert" (M = 30.1 ml/ kg/ min, SD = 5.0; p = 0.009) und solchen in der Klasse "Hoch, verringert" (M = 29.6 ml/ kg/ min, SD = 5.9; p = 0.032). Es wurden keine Unterschiede zwischen den anderen Klassen gefunden. Die Ergebnisse des zweiten Artikels weisen darauf hin, dass in allen Regressionsmodellen nur Fernsehen positiv mit einem CMRS assoziiert war. In Abhängigkeit von dem gewählten Regressionsverfahren ergaben sich für andere Sitzverhaltensweisen, die in der Freizeit gezeigt werden, hingegen inkonsistente Ergebnisse (Nutzung eines Computers) oder keine Assoziationen (Lesen und Zeit mit anderen Personen verbringen) mit einem CMRS. Die Ergebnisse des dritten Artikels zeigten, dass über beide Tragezeiträume (baseline und nach 12 Monaten) die sitzend verbrachte Zeit um 2.3 min/ Tag beziehungsweise 3.8 min/ Tag zunahm und leichte körperliche Aktivität um 2.0 min/ Tag beziehungsweise 3.3 min/ Tag abnahm. Die Tragezeit des Akzelerometers reduzierte sich nur zu Baseline um 4.6 min/ Tag. Der Umfang moderater bis anstrengender körperlicher Bewegung änderte sich weder zu Baseline noch nach 12 Monaten. Die ICC-Koeffizienten reichten von 0.42 (95% CI = 0.29 – 0.57) für die Tragezeit des Akzelerometers bis 0.70 (95% CI = 0.61 – 0.78) für moderate bis anstrengende körperlicher Aktivität. Ein Reaktivitätsindikator konnte in keinem Regressionsmodell als konfundierender Faktor für die Reproduzierbarkeit von Sitz- und Aktivitätsdaten identifiziert werden. Schlussfolgerung: Die vorliegende Arbeit untersuchte das Sitzverhalten von Personen im Rahmen der kardiovaskulären und kardiometabolischen Gesundheitsforschung. Es können hieraus Implikationen sowie zukünftiger Forschungsbedarf in diesem Gebiet abgeleitet werden. In zukünftigen Studien sollte berücksichtigt werden, dass Sitzen nicht losgelöst auftritt, sondern in das alltägliche Leben eines Individuums eingebettet ist. Personen sitzen aus verschiedenen Gründen in mehreren Lebensbereichen und die im Sitzen verbrachte Zeit ist von Person zu Person und von Tag zu Tag unterschiedlich zusammengesetzt. Dies kann unterschiedliche Auswirkungen auf die kardiovaskuläre und kardiometabolische Gesundheit haben. Ferner ist eine genaue Messung von Sitzverhalten von grundlegender Bedeutung, um festzustellen, inwiefern das Sitzverhalten "unabhängig" von anderen Einflussfaktoren mit der Gesundheit eines Individuums assoziiert ist. Darüber hinaus sollten konfundierende Faktoren wie beispielsweise Reaktivität in der Planung von Studien sowie bei der Interpretation von Sitz- und Aktivitätsdaten berücksichtigt werden

Application of the Soil and Water Assessment Tool (SWAT) to predict the impact of alternative management practices on water quality and quantity

Alternative land management practices such as conservation or no-tillage, contour farming, terraces, and buffer strips are increasingly used to reduce nonpoint source and water pollution resulting from agricultural activities. Models are useful tools to investigate effects of such management practice alternatives on the watershed level. However, there is a lack of knowledge about the sensitivity of such models to parameters used to represent these conservation practices. Knowledge about the sensitivity to these parameters would help models better simulate the effects of land management. Hence, this paper presents in the first step a sensitivity analysis for conservation management parameters (specifically tillage depth, mechanical soil mixing efficiency, biological soil mixing efficiency, curve number, Manning's roughness coefficient for overland flow, USLE support practice factor, and filter strip width) in the Soil and Water Assessment Tool (SWAT). With this analysis we aimed to improve model parameterisation and calibration efficiency. In contrast to less sensitive parameters such as tillage depth and mixing efficiency we parameterised sensitive parameters such as curve number values in detail. In the second step the analysis consisted of varying management practices (conventional tillage, conservation tillage, and no-tillage) for different crops (spring barley, winter barley, and sugar beet) and varying operation dates. Results showed that the model is very sensitive to applied crop rotations and in some cases even to small variations of management practices. But the different settings do not have the same sensitivity. Duration of vegetation period and soil cover over time was most sensitive followed by soil cover characteristics of applied crops.SWAT Tillage management practice Conservation tillage Water balance Nutrient Modelling

NorM, an Erwinia amylovora Multidrug Efflux Pump Involved in In Vitro Competition with Other Epiphytic Bacteria

Blossoms are important sites of infection for Erwinia amylovora, the causal agent of fire blight of rosaceous plants. Before entering the tissue, the pathogen colonizes the stigmatic surface and has to compete for space and nutrient resources within the epiphytic community. Several epiphytes are capable of synthesizing antibiotics with which they antagonize phytopathogenic bacteria. Here, we report that a multidrug efflux transporter, designated NorM, of E. amylovora confers tolerance to the toxin(s) produced by epiphytic bacteria cocolonizing plant blossoms. According to sequence comparisons, the single-component efflux pump NorM is a member of the multidrug and toxic compound extrusion protein family. The corresponding gene is widely distributed among E. amylovora strains and related plant-associated bacteria. NorM mediated resistance to the hydrophobic cationic compounds norfloxacin, ethidium bromide, and berberine. A norM mutant was constructed and exhibited full virulence on apple rootstock MM 106. However, it was susceptible to antibiotics produced by epiphytes isolated from apple and quince blossoms. The epiphytes were identified as Pantoea agglomerans by 16S rRNA analysis and were isolated from one-third of all trees examined. The promoter activity of norM was twofold greater at 18°C than at 28°C. The lower temperature seems to be beneficial for host infection because of the availability of moisture necessary for movement of the pathogen to the infection sites. Thus, E. amylovora might employ NorM for successful competition with other epiphytic microbes to reach high population densities, particularly at a lower temperature