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A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols ([less than or equal to]10 [micro]m) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host-pathogen interactions. Culturable Mycobacterium tuberculosis can be detected in cough aerosol from a high proportion of individuals infected with drug-resistant M. tuberculosis and correlate with a strong cough and low symptom score, indicating the need to focus on targeted interventions., Author(s): Grant Theron [sup.1] [sup.2] , Jason Limberis [sup.1] , Rouxjeane Venter [sup.2] , Liezel Smith [sup.1] [sup.2] , Elize Pietersen [sup.1] , Aliasgar Esmail [sup.1] , Greg Calligaro [sup.1] [...]

The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from that of the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically the bacteroidetes species. Targeting bacteroidetes with oral antibiotics reduced hepatic immune cells by approximately 90%, prevented antigen-presenting cell (APC) maturation, and mitigated adaptive immunity. Mechanistically, our findings are consistent with presentation of bacteroidetes-derived glycosphingolipids to NKT cells promoting CCL5 signaling, which drives hepatic leukocyte expansion and activation, among other possible host-microbe interactions. Collectively, we reveal a microbial/glycosphingolipid/NKT/CCL5 axis that underlies hepatic immunity., Introduction Gut microbiota represent the most abundant and diverse collection of commensal organisms in the body (1). The intestinal microbiome plays a fundamental role in shaping the host immune system [...]

BACKGROUND. Although recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses. METHODS. Here, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus. RESULTS. In both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients. CONCLUSION. Our findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection. TRIAL REGISTRATION. ISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study)., Introduction Despite the widespread global effects of the coronavirus disease 2019 (COVID-19) pandemic, few reports have assessed potential interactions between upper airway bacterial colonization and severe acute respiratory syndrome coronavirus [...]

A close association with its vertebrate and tick hosts allows Borrelia burgdorferi, the bacterium responsible for Lyme disease, to eliminate many metabolic pathways and instead scavenge key nutrients from the host. A lipid-defined culture medium was developed to demonstrate that exogenous lipids are an essential nutrient of B. burgdorferi, which can accumulate intact phospholipids from its environment to support growth. Antibody responses to host phospholipids were studied in mice and humans using an antiphospholipid ELISA. Several of these environmentally acquired phospholipids including phosphatidylserine and phosphatidic acid, as well as borrelial phosphatidylcholine, are the targets of antibodies that arose early in infection in the mouse model. Patients with acute infections demonstrated antibody responses to the same lipids. The elevation of antiphospholipid antibodies predicted early infection with better sensitivity than did the standardized 2-tier tests currently used in diagnosis. Sera obtained from patients with Lyme disease before and after antibiotic therapy showed declining antiphospholipid titers after treatment. Further study will be required to determine whether these antibodies have utility in early diagnosis of Lyme disease, tracking of the response to therapy, and diagnosis of reinfection, areas in which current standardized tests are inadequate., Introduction With an average genome of approximately 1.3 mbp (1), many aspects of cellular metabolism are minimized or absent in Borrelia burgdorferi. Such an evolutionary genome reduction is possible because [...]

Conventional ubiquitination regulates key cellular processes by catalysing the ATP-dependent formation of an isopeptide bond between ubiquitin (Ub) and primary amines in substrate proteins.sup.1. Recently, the SidE family of bacterial effector proteins (SdeA, SdeB, SdeC and SidE) from pathogenic Legionella pneumophila were shown to use NAD.sup.+ to mediate phosphoribosyl-linked ubiquitination of serine residues in host proteins.sup.2, 3. However, the molecular architecture of the catalytic platform that enables this complex multistep process remains unknown. Here we describe the structure of the catalytic core of SdeA, comprising mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains, and shed light on the activity of two distinct catalytic sites for serine ubiquitination. The mART catalytic site is composed of an [alpha]-helical lobe (AHL) that, together with the mART core, creates a chamber for NAD.sup.+ binding and ADP-ribosylation of ubiquitin. The catalytic site in the PDE domain cleaves ADP-ribosylated ubiquitin to phosphoribosyl ubiquitin (PR-Ub) and mediates a two-step PR-Ub transfer reaction: first to a catalytic histidine 277 (forming a transient SdeA H277-PR-Ub intermediate) and subsequently to a serine residue in host proteins. Structural analysis revealed a substrate binding cleft in the PDE domain, juxtaposed with the catalytic site, that is essential for positioning serines for ubiquitination. Using degenerate substrate peptides and newly identified ubiquitination sites in RTN4B, we show that disordered polypeptides with hydrophobic residues surrounding the target serine residues are preferred substrates for SdeA ubiquitination. Infection studies with L. pneumophila expressing substrate-binding mutants of SdeA revealed that substrate ubiquitination, rather than modification of the cellular ubiquitin pool, determines the pathophysiological effect of SdeA during acute bacterial infection.Structural and functional investigations demonstrate how bacterial enzymes ubiquitinate host proteins., Author(s): Sissy Kalayil [sup.1] [sup.2] , Sagar Bhogaraju [sup.1] [sup.2] , Florian Bonn [sup.1] , Donghyuk Shin [sup.1] [sup.2] , Yaobin Liu [sup.1] [sup.2] , Ninghai Gan [sup.3] , Jérôme [...]

In view of emerging drug-resistant tuberculosis (TB), host-directed adjunct therapies are urgently needed to improve treatment outcomes with currently available anti-TB therapies. One approach is to interfere with the formation of lipid-laden 'foamy' macrophages in the host, as they provide a nutrient-rich host cell environment for Mycobacterium tuberculosis (Mtb). Here, we provide evidence that Wnt family member 6 (WNT6), a ligand of the evolutionarily conserved Wingless/Integrase 1 (WNT) signaling pathway, promotes foam cell formation by regulating key lipid metabolic genes including acetylCoA carboxylase 2 (ACC2) during pulmonary TB. Using genetic and pharmacological approaches, we demonstrated that lack of functional WNT6 or ACC2 significantly reduced intracellular triacylglycerol (TAG) levels and Mtb survival in macrophages. Moreover, treatment of Mtb-infected mice with a combination of a pharmacological ACC2 inhibitor and the anti-TB drug isoniazid (INH) reduced lung TAG and cytokine levels, as well as lung weights, compared with treatment with INH alone. This combination also reduced Mtb bacterial numbers and the size of mononuclear cell infiltrates in livers of infected mice. In summary, our findings demonstrate that Mtb exploits WNT6/ACC2-induced storage of TAGs in macrophages to facilitate its intracellular survival, a finding that opens new perspectives for host-directed adjunctive treatment of pulmonary TB., Introduction Tuberculosis (TB) is the leading cause of death from a single bacterial agent (1). The current increase in numbers of patients affected by multidrug-resistant and rifampicin-resistant TB (2) severely [...]

Herein, we describe an extracellular function of the vertebrate high-mobility group box 1 protein (HMGB1) in the proliferation of bacterial biofilms. Within host cells, HMGB1 functions as a DNA architectural protein, similar to the ubiquitous DNABII family of bacterial proteins; despite that, these proteins share no amino acid sequence identity. Extracellularly, HMGB1 induces a proinflammatory immune response, whereas the DNABII proteins stabilize the extracellular DNA-dependent matrix that maintains bacterial biofilms. We showed that when both proteins converged on extracellular DNA within bacterial biofilms, HMGB1, unlike the DNABII proteins, disrupted biofilms both in vitro (including the high-priority ESKAPEE pathogens) and in vivo in 2 distinct animal models, albeit with induction of a strong inflammatory response that we attenuated by a single engineered amino acid change. We propose a model where extracellular HMGB1 balances the degree of induced inflammation and biofilm containment without excessive release of biofilm-resident bacteria., Introduction Bacteria within a human host prefer a community architecture, also known as a biofilm. Biofilms form when free-living (planktonic) bacteria adhere to each other (aggregate biofilms) or adhere to [...]

Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars (1), increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse (2,3). These antibiotic-induced changes in the gut microbiota can be studied in mice, in which the disruption of a balanced microbial community by treatment with the antibiotic streptomycin leads to an expansion of S. enterica serovars in the large bowel (4). However, the mechanisms by which streptomycin treatment drives an expansion of S. enterica serovars are not fully resolved. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovar Typhimurium (S. Typhimurium). By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the caecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine caecum. S. Typhimurium used galactarate and glucarate within the gut lumen of streptomycin pre-treated mice, and genetic ablation of the respective catabolic pathways reduced S. Typhimurium competitiveness. Our results identify host-mediated oxidation of carbohydrates in the gut as a mechanism for post-antibiotic pathogen expansion., A recent in silico analysis suggests that pathways involved in galactarate uptake and catabolism are associated with S. enterica serovars that cause gastrointestinal disease (5). Galactarate fermentation is one of [...]

Within the bivalve family Thyasiridae, symbioses with chemoautotrophic, sulphur-oxidizing bacteria do not occur in all lineages; variation in symbiont presence and in the degree of abfrontal expansion of gill filaments occurs on fine phylogenetic scales within the family. Thyasirid symbionts are harboured extracellularly and are periodically engulfed and digested by host gill epithelial cells. Symbiotic thyasirids are mixotrophic, retaining the capacity to feed on particulate matter; the relative importance of particulate feeding and symbiont-derived nutrition to host metabolism may vary on temporal and spatial scales depending on the abundance of particulate organic matter and sediment sulphide availability. Here, we demonstrate the existence of a temporal trend in symbiont abundance in Thyasira cf. gouldi from Bonne Bay, Newfoundland, Canada, over 18 months (2011 and 2012): symbiont abundance is highest during the months of autumn and is lowest in spring. The density of membrane whorls, lysosomal microbodies associated with the digestion of bacterial symbionts, does not display a similar temporal trend, indicating that relationships between the contribution of symbiont-derived nutrition and seasonal fluctuations in environmental parameters are less clear. Along with the extracellular status of thyasirid symbioses, their highly dynamic nature may explain the possible evolutionary loss or gain of chemosymbioses among some members of this group. Electronic supplementary material The online version of this article (doi:10.1007/s00227-015-2727-4) contains supplementary material, which is available to authorized users., Author(s): Jason R. Laurich[sup.1] , Rebecca T. Batstone[sup.1] , Suzanne C. Dufour[sup.1] Author Affiliations: (1) Department of Biology, Memorial University of Newfoundland, A1B 3X9, St. John's, NL, Canada Introduction Symbioses [...]

Leaves of higher plants comprise perhaps the largest bacterial substrate on earth, yet we know very little about the bacteria that occupy these spaces. In this review, we first examine the ecology and behavior of bacteria that reside on leaf surfaces. Next, we discuss the ecological implications of foliar bacteria that reside in interior portions of leaf tissues. Later, we consider the studies on foliar bacteria in tropical habitats to date. Finally, we examine evidence regarding the potential roles of foliar bacteria in structuring tropical plant communities. Bacteria colonize the phyllosphere via animal vectors or passively from soil, wind, or rain, though there are too few data to determine the relative contributions of these sources to the phyllosphere. Additionally, the degree to which parent plants transmit bacteria to offspring via seed remains unknown. We predict that high temperature, high humidity, low UV radiation, and leaf architecture in the tropical understory enable tropical leaves to support more abundant and diverse bacterial communities compared to temperate leaves. While the extent of competitive interactions among bacteria remains poorly resolved, evidence from agricultural crop species and Arabidopsis thaliana suggests that these interactions cause niche partitioning based on carbon use. The degree to which phyllobacteria and endophytes of tropical plants are pathogenic versus mutualistic or neutral remains unexplored. We hypothesize, however, that the detrimental impact of bacterial pathogens ultimately increases as the abundance of single host tree species increases, which can promote and maintain plant diversity in tropical forests. Las hojas de las plantas superiores constituyen posiblemente el sustrato bacteriologico mas extenso en el planeta, sin embargo sabemos muy poco sobre las bacterias que ocupan estos espacios. En este articulo examinamos, en primer lugar, la ecologia y el comportamiento de las bacterias que residen en las superficies de las hojas. Luego, discutimos las implicaciones ecologicas de las bacterias foliares que residen en el interior de los tejidos de las hojas. Ademas, consideramos los estudios sobre bacterias foliares en habitats tropicales a la fecha. Finalmente examinamos la evidencia que existe sobre el potencial impacto de las bacterias foliares en la estructura de comunidades de plantas tropicales. Las bacterias generalmente colonizan la filosfera a traves de vectores animales o pasivamente a traves del suelo, el viento o la lluvia, aunque hay poca informacion para determinar la contribucion relativa de estas fuentes a la filosfera. Adicionalmente, no se sabe hasta que punto ocurre una transmision bacteriana de progenitor a progenie a traves de semillas. Predecimos que las altas temperaturas, la elevada humedad, la baja radiacion ultravioleta, y la arquitectura de las hojas en el sotobosque permiten que las hojas tropicales contengan comunidades bacteriologicas mas abundantes y diversas en comparacion con hojas de clima templado. Aunque el grado de interacciones competitivas entre bacterias aun no ha sido bien entendido, evidencia de especies de interes agronomico y Arabiclopsis thaliana sugiere que estas interacciones causan particiones de nicho basadas en el uso de carbono. La naturaleza patogena, mutualista o neutra de las filobacterias y bacterias endofitas de plantas tropicales no se ha explorado hasta el momento. Nuestra hipotesis es, sin embargo, que el impacto negativo de patogenos bacterianos es mayor con el incremento en la abundancia de huespedes especificos, lo que puede promover y mantener la diversidad de plantas en los bosques tropicales. Keywords Foliarbacteria * Tropical forests * Agroecosystems * Plant diversity-Microbial ecology * Plant coexistence * Endophytes * Pathogens, Table of Contents I. Abstract I. Introduction A. Definitions III. Bacterial colonization and recruitment to the phyllosphere A. From soil to seedling 1. Mechanical chauffeuring B. Wind and rain C. [...]

Mollusks, and particularly gastropods, are one of the major taxonomic groups at vents. In these ecosystems, devoid of light, chemoautotrophic bacteria are at the base of the food web and symbiotic association between metazoa and these bacteria is numerous. Nevertheless, apart few 'large-size' well-known species, the 'small-size' gastropods (shell < 5 mm), although very abundant, remain poorly studied regarding symbioses. We investigated here Cyathermia naticoides (Waren and Bouchet in Zool Scr 18(1), 1989), a small coiled gastropod found in abundance on the East Pacific Rise among Riftia pachyptila tubes, and usually inferred to graze on tubeworm bacterial cover, and/or filter feeding. Among mollusks, symbioses are well known in large species and almost exclusively rely on sulfide or methane-oxidizing proteobacterial endosymbionts, occurring within the host tissues in gill epithelial bacteriocytes. Combining several approaches (molecular biology, microscopy, stable isotopes analyses), we described here an unusual symbiosis, where autotrophic filamentous Epsilonproteobacteria are located extracellularly, at the base of host gill filaments. Numerous endocytotic lysosome-like structures were observed in the gill epithelium of the animal suggesting bacteria may contribute to its nutrition through intracellular digestion by gill cells. Additional food source by non-symbiotic proteobacteria grazed on R. pachyptila tubes could complete the diet. The possible role of temperature in the selection of Epsilon- vs Gammaproteobacterial partners is discussed., Introduction To date, about 600 metazoan species have been reported at hydrothermal vents, belonging to 12 phyla. Among those, 150 species of molluska and more than 100 species of Gastropoda [...]

PU19.01 The impact of vaginal Lactobacillus isolates on host gene expression involved in inflammation in the female genital tract A. Abrahams (1) ; M.T. Manhanzva (2) ; A. Alisoltani (3) [...]

Author(s): John D. MacMicking (corresponding author) [1] Pathogenic microbes that invade a human host must overcome many obstacles to establish infection. One of the first is an immune response known [...]

The collection of bacteria, viruses, and fungi that live in and on the human body, collectively known as the microbiome, has recently emerged as an important factor in human physiology and disease. The gut in particular is a biological niche that is home to a diverse array of microbes that influence nearly all aspects of human biology through their interactions with their host; new technologies are beginning to reveal important aspects of host-microbe interactions. Articles in this Review series address how perturbations of the microbiota, such as through antibiotic use, influence its overall structure and function; how our microbiome influences the impact of infectious agents, such as C. difficile; how our microbiome mediates metabolism of xenobiotics; how the microbiota contribute to immunity as well as to metabolic and inflammatory diseases; and the role of commensal microbes in oncogenesis., Until recently, the population of microbes in and on the human body was mostly considered to be vast and largely unknowable. It was referred to as 'the normal flora,' the [...]

Our group recently discovered that certain dietary nutrients possessing a trimethylamine (TMA) moiety, namely choline/ phosphatidylcholine and L-carnitine, participate in the development of atherosclerotic heart disease. A meta-organismal pathway was elucidated involving gut microbiota-dependent formation of TMA and host hepatic flavin monooxygenase 3-dependent (FMO3-dependent) formation of TMA-W-oxide (TMAO), a metabolite shown to be both mechanistically linked to atherosclerosis and whose levels are strongly linked to cardiovascular disease (CVD) risks. Collectively, these studies reveal that nutrient precursors, gut microbiota, and host participants along the meta-organismal pathway elucidated may serve as new targets for the prevention and treatment of CVD., Introduction Cardiovascular disease (CVD) remains the leading cause of death in both the United States and industrialized societies, with growing incidence in developing countries (1). Factors contributing to CVD arise [...]

A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would [...]

Predation by the crown-of-thorns seastar (CoTS; Acanthaster sp.) is a pervasive stressor attributing to the decline of coral reefs. These outbreaks are suggested to be linked to eutrophy-driven recruitment pulses, where increased nutrients enhance larval success. CoTS larvae, however, are tolerant of oligotrophic conditions typical of tropical ecosystems and outbreaks occur in regions isolated from eutrophy, highlighting the resilience of these larvae to oligotrophic conditions. Here, we test the hypothesis that CoTS larvae associate with bacterial communities that are dynamic across an oligotrophic-eutrophic continuum and are specific to each feeding regime. Our analysis of the CoTS larval microbiome suggests that CoTS larvae associate with a bacterial community distinct from the environmental microbiota and that this community experiences a community-level shift in response to differential feeding that is maintained over development. Symbioses with a diverse and dynamic, and a potentially phototrophic, bacterial community may contribute to resilience of CoTS larvae that enable the success of CoTS and, perhaps, other tropical marine larvae in oligotrophic seas., Author(s): Tyler J. Carrier [sup.1] , Kennedy Wolfe [sup.2] , Karen Lopez [sup.3] , Mailie Gall [sup.2] , Daniel A. Janies [sup.3] , Maria Byrne [sup.2] [sup.4] , Adam M. [...]

Background Both typhoidal and non-typhoidal Salmonella infections remain a considerable cause of morbidity and mortality globally, and impose a major socio-economic burden worldwide. A key property of all pathogenic Salmonella strains is the ability to invade host cells and reside within an intracellular, vacuolar compartment called the Salmonella-containing vacuole (SCV). Although the SCV is involved in both immune-evasion and intracellular replication and spread within the host, information about the host:pathogen interactions at this interface are limited, in part due to the technical difficulties involved in purification of these vacuoles. While a number of column- or gradient-based methods have been applied, cross-contamination with other host cell organelles or rupture of the labile SCV membrane has further complicated efforts to successfully isolate SCVs. Results Here, we report the isolation of intact SCVs using carbon-coated, paramagnetic nanoparticles. The approach permits rapid isolation of intact SCVs from human macrophages in vitro without involving numerous purification steps. Bacteria are pre-labeled with modified nanoparticles prior to infection, and at various times post-infection, host cells are lysed and intact pathogen-containing phagosomes are recovered after application of a mild magnetic field. Purified, intact SCVs isolated using this method were shown to display high levels of co-association of internalized Salmonella with the standard SCV markers Rab5 and LAMP-1 using both microscopic and protein based methods. Conclusion The method described is highly efficient, robust and permits rapid isolation of intact SCVs from human macrophages without involving numerous purification steps. The method can also be applied to other intracellular pathogens that reside within a vacuole-like compartment within host cells. Future work using the approach should aid in identification and characterization of host factors associated with the membranes of such intracellular pathogens, which could potentially serve as pharmaceutical targets against intracellular pathogens residing within vacuoles. Keywords: Nanoparticles, Bacteria containing phagosome, Isolation, Salmonella, Infection, Macrophages, Author(s): Vikash Singh[sup.1,2] , Peter Schwerk[sup.1] and Karsten Tedin[sup.1] Background Salmonella enterica serovars are Gram-negative, facultative intracellular bacteria that infect and colonize vertebrate hosts with outcomes ranging from sub-clinical infections [...]

Background Campylobacter jejuni is considered as a chicken commensal. The gut microbiota and the immune status of the host may affect its colonization. Infectious bursal disease virus (IBDV) is an immunosuppressive virus of chickens, which allows secondary pathogens to invade or exacerbates their pathogenesis. To investigate the effect of IBDV-induced immunosuppression on the pathogenesis of C. jejuni, broiler chickens were inoculated with a very virulent (vv) strain of IBDV at 14 days post hatch followed by C. jejuni inoculation at 7 (Experiment A) or 9 (Experiment B) days post virus (IBDV) inoculation. Results vvIBDV-infection led to a depression in caecal lamina propria B lymphocytes and the anti-C. jejuni-antibody response starting at 14 days post C. jejuni inoculation (pbi). The C. jejuni-colonization pattern was comparable between mono-inoculated groups of both experiments, but it varied for vvIBDV + C. jejuni co-inoculated groups. In Experiment A significant higher numbers of colony forming units (CFU) of C. jejuni were detected in the caecum of co-inoculated birds compared to C. jejuni-mono-inoculated birds in the early phase after C. jejuni-inoculation. In Experiment B the clearance phase was affected in the co-inoculated group with significantly higher CFU at 21 days pbi compared to the mono-inoculated group (P < 0.05). No major differences were seen in numbers local lamina propria T lymphocyte populations between C. jejuni-inoculated groups with or without vvIBDV-infection. Interestingly, both pathogens affected the microbiota composition. The consequences of these microflora changes for the host have to be elucidated further. Conclusion Our data suggests that the timing between viral and bacterial infection might affect the outcome of C. jejuni colonization differently. Our results confirm previous studies that anti-Campylobacter-antibodies may specifically be important for the clearance phase of the bacteria. Therefore, as vvIBDV is widely distributed in the field, it may have a significant impact on the colonization and shedding rate of C. jejuni in commercial poultry flocks. Subsequently, successful IBDV-control strategies may indirectly also benefit the gut-health of chickens. Keywords: Campylobacter jejuni, Infectious bursal disease virus, Immunosuppression, Immune response, Gut microbiota composition, Author(s): Li Li[sup.1] , Colin Pielsticker[sup.1] , Zifeng Han[sup.1] , Tereza Kubasová[sup.2] , Ivan Rychlik[sup.2] , Bernd Kaspers[sup.3] and Silke Rautenschlein[sup.1] Background Campylobacter jejuni is the leading cause of bacterial [...]