Aerogenic Infection Research Articles

Dopaminergic neuronal regulation determines innate immunity of Caenorhabditis elegans during Klebsiella aerogenes infection

The innate immune signals are the front line of host defense against bacterial pathogens. Pathogen-induced harmful effects, such as reduced neuronal signals to the intestine, affect the host's food sensing and dwelling behavior. Here, we report that dopamine and kpc-1 signals control the intestinal innate immune responses through the p38/PMK-1 MAPK signaling pathway in C. elegans. K. aerogenes infection in C. elegans affects the food-dwelling behavior, which depends on dopamine regulation. The absence of the dopamine receptor (dop-1) and transporter (dat-1) increases attraction to the pathogen instead of avoidance. The K. aerogenes infection affects age-1 regulation through the furin-like proprotein convertase (kpc-1); the absence of kpc-1 affects environment-dependent dauer formation. In contrast, the dop-1 mutation antagonistically regulates intestinal immune regulation, while the kpc-1 mutation partially regulates the p38/PMK-1 MAPK pathway. Our findings indicate that dopamine and kpc-1signaling from the nervous system control intestinal immunity in an antagonistic and agonistic manner, respectively.

ОБОСНОВАНИЯ ПО ПРИМЕНЕНИЮ ОПЫТА ПРОТИВОТУБЕРКУЛЁЗНОЙ СЛУЖБЫ ДЛЯ АДЕКВАТНОГО РЕАГИРОВАНИЯ В ПЕРИОД ПАНДЕМИИ COVID-19

Objective: To summarize the experience of the anti-tuberculosis care (ATC) units of the Republic of Tajikistan (RT) to optimize medical aid to the population during potential outbreaks of respiratory infectious diseases. Methods: This study examines the experience and lessons learned after the COVID-19 pandemic in the RT, as well as the main provisions recommended for the partial reorganization of the ATC to ensure its readiness to function during outbreaks of respiratory infections. The standards and rules of antituberculosis infection control were used to develop preventive measures against the nosocomial spread of aerogenic infections in healthcare facilities and society. Results: The analysis revealed that maintaining of a sanitary and anti-epidemic regimen in healthcare institutions primarily involved a routine approach to the disinfection of medical facilities. However, in respiratory infections, adopting the experience of ATC RT was beneficial. It included strict adherence to infection control rules, social distancing, avoidance of crowded public places, restriction of unnecessary migration and public events, and the rigorous use of means of personal protection. The ATC also pioneered innovative approaches through various software, which have proven effective even under the restrictions imposed during the COVID-19 pandemic. Conclusion: ATC can serve as a coordinating link and an excellent example of how to prepare the healthcare system for various potential outbreaks of respiratory infections. It is necessary to integrate the ATC with other relevant institutions of the healthcare system, both functionally and structurally, to increase the effectiveness of preventive measures against the transmission of respiratory infections. Keywords: TB care, health care facilities, COVID-19, respiratory infections.

Regulation of miR-61 and col-19 via TGF-β and Notch signalling in Caenorhabditis elegans against Klebsiella aerogenes infection

Klebsiella aerogenes, previously known as Enterobacter aerogenes, is a gram-negative bacterium typically present in the gastrointestinal tract. While numerous studies reported the pathogenicity and drug resistance of this bacterium there remains a lack of comprehensive research on K. aerogenes induced alterations in the host cellular mechanisms. In this study, we identify a previously uncharacterized C. elegans miR-61 that defines an evolutionarily conserved miRNA important for development and innate immunity regulation through Notch and TGF-β signaling pathway. We employed C. elegans wild-type (N2) as well as mutant strains, such as TGF-β (sma-6) and notch-signaling pathway mutants (adm-4 and mir-61). Our results have demonstrated that the K. aerogenes infected mutants exhibited significantly reduced survival rate, reduced pharyngeal pumping, altered swimming and chemotactic behavior. Moreover, K. aerogenes affects the healthspan by increasing ROS level in the mutants. The gene expression analysis revealed that K. aerogenes upregulated egl-30, tph-1 and sod-1 in adm-4, mir-61 mutants not in sma-6. The in-silico analysis indicated an interaction between mir-61 and col-19, which was confirmed by the upregulation of miR-61 expression and the downregulation of col-19 in sma-6, adm-4, and wild-type strains. These findings suggest that C. elegans activates mir-61 and col-19 regulation through the Notch and TGF-β signaling pathway against K. aerogenes infection.

State of the Lung Microbiota in С57bl/6 Mice in the Experimental Tuberculosis Model

The objective: to study the changes in the lung microbiota in inbred C57BL/6 mice after aerogenic infection with M. tuberculosis in an experimental tuberculosis model.Subjects and Methods. This study was carried out on 20 female mice of inbred line C57BL/6 weighing 20-22 grams which were infected in a Glas-Col aerosol chamber (USA) with the culture of M. tuberculosis of virulent strain H37Rv at the dose of 400 CFU/lung. Morphological and microbiological assessment of the lungs state was performed before (day 0) (n=5) and 7 (n=5), 30 (n=5) and 60 (n=5) days after the infection. The results obtained were subjected to statistical processing using ANOVA test and Student t-test.Results. 7, 30, and 60 days after aerosol infection with M. tuberculosis against the background of successive morphological and microbiological changes typical of the experimental tuberculosis model, we established an imbalance of bacterial population in the lung microbiota. Before infection with M. tuberculosis, a scanty biotope was recorded with a predominance of lactobacilli –Lactobacillus murinus, Lactobacillus apodeme. 7, 30 and 60 days after infection with M. tuberculosis, consistent changes were recorded, such as increase in the number and diversity of the bacterial population. The most indicative markers of the recorded imbalance were: Streptococcus thoraltensis, Streptococcus acidominiminus, Arthrobacter crystallopoietes, Staphylococcus hominis, Micrococcus luteus.Conclusion. Tuberculosis infection is a significant factor affecting the state of the lung microbiota. With increased duration of the infection with M. tuberculosis, imbalance of the bacterial flora is formed in the lungs of C57BL/6 mice, accompanied by characteristic tissue inflammation and growing mycobacterial load.

Fountains as potential sources of aerogenic risk for urban populations

Introduction. Fountains (office and outdoor), being small decorative structures used to improve the parameters of the human life environment, in the process of their work during the generation of a water jet, determine the creation of spray and aerosol fractions, thereby allowing the loss of a certain volume of liquid when air moves and wind carryover. The biological safety of the operation of such hydraulic structures depends on the composition of the microflora of the water in the main reservoir of the fountain, especially in the warm season. Materials and methods. For the period 2010-2020, the study of the composition of the microflora of water in the main reservoirs of the existing fountains and in the sedimented spray-aerosol mixture formed during the operation of these hydraulic structures was carried out. Results. At water temperatures above +18 °C and the absence of a disinfection system or its regular complete replacement, fountains were found to have a significant level of contamination with bacterial and fungal pathogens, including mycobacterium tuberculosis; the number of microorganisms of the E. coli group in office and open city fountains. The amount of Clostridial flora and streptococci in open fountains significantly exceeds the standard indicators (p <0.05). Limitations. When studying the trends in concentration of liquid particles in the air, the methodology of K.Y. Kondratiev et al. (1988) and V.M. Khvata et al. (1991) was used. The studies were carried out in accordance with the Interstate standard “Water. Methods of sanitary and bacteriological analysis for field conditions” GOST 24849-2014, 2016. Conclusion. The microflora of the operating fountain, in the absence of disinfection of water or its regular replacement, is characterized by a high titer of bacteria of the E. coli group, streptococci, staphylococci, mycobacterium tuberculosis, mold and yeast fungi. The one of the conditions for the excessive growth of these microorganisms in this hydraulic system is the water temperature above 18 °C. In the sedimented aerosol near the active fountain, a bacterial and fungal spectrum of pathogenic microorganisms similar to the water is found. Fountains (external and office) can be considered as sources of aerogenic household infection of the population of modern cities, which requires strict adherence to sanitary norms and rules that ensure the biological safety of these hydraulic structures.

Spore-Trapping Device: An Efficient Tool to Manage Fungal Diseases in Winter Wheat Crops.

Leaf airborne diseases cause major shortfalls in agricultural crops. The introduction of technical means can significantly improve early-warning systems for plant diseases as well as provide timely and accurate forecasts. In this paper, we aim to evaluate the possibilities of detecting a phytopathogenic infection using a spore-catching device developed at the Federal Research Center of Biological Plant Protection (FRCBPP) on winter wheat varieties of different levels of susceptibility to major economically important leaf diseases, taking into account climatic conditions. The device captures spores in the surface layer of air among crop plants. We conducted research in the experimental fields of FRCBPP in 2019-2021. The objects of the study were four cultivars of winter wheat. They were selected according to the degree of resistance to various leaf diseases. We studied the progress of wheat diseases according to generally accepted international scales the onset of the first manifestations to their maximum development. We studied the aerogenic infection in wheat crops using the FRCBPP developed portable device for determining the infestation of plants. Sampling was carried out in the same period as the visual assessment. The samples were taken in the crops of each variety at five points. The sampling time was one minute. As a result of research on experimental crops of four varieties of winter wheat, we observed the development of such diseases as powdery mildew (Erysiphe graminis), yellow spot (Pyrenophora tritici-repentis), septoria leaf spot (Septoria tritici), yellow (Puccinia striiformis) and brown rust (Puccinia triticina). In a laboratory study of samples under a light microscope, all of the listed pathogens were found except for septoria leaf spot. Two-way analysis of variance confirmed the statistically significant separate and cumulative influence of the cultivar and year factor on winter wheat diseases. A generalized correlation analysis for three growing seasons (2019-2021) showed that an average statistically significant correlation coefficient (0.5-0.6) remains for the total groups for powdery mildew, yellow and brown rust. This indicator for the causative agent of yellow spot was equal to 0.4 with a high level of statistical significance. Thus, we conclude that by using a spore-catching device, it is possible to identify spores of economically significant pathogens in winter wheat crops and predict the further development of pathogens, taking into account the cultivar and annual climate factors.

A case report of Klebsiella aerogenes-caused lumbar spine infection identified by metagenome next-generation sequencing

BackgroundThe early clinical diagnosis of spinal infections in elderly patients with recessive or atypical symptoms is difficult. Klebsiella aerogenes is a common opportunistic bacterium that can infect the respiratory tract, urinary tract, and even the central nervous system. However, whether it can infect the lumbar spine has not been previously described.Case presentationIn this paper, we report the case of a 69-year-old female patient with osteoporosis who was initially diagnosed with hemolytic anemia. Later, she was diagnosed with K. aerogenes infection of the lumbar spine based on imaging combined with blood culture and metagenome next-generation sequencing (mNGS) detection. After precise medication, the lumbar degeneration was improved.ConclusionsBacterial infection should therefore be considered in cases of lumbar degenerative disease in middle-aged and elderly patients.

Development of an aerogenous Escherichia coli infection model in adult broiler breeders

Escherichia coli constitutes an immense challenge to the poultry industry due to its devastating effect on productivity, mortality, and carcass condemnations. To aid future studies on disease mechanisms and interventions, an aerogenous infection model was established in adult broiler breeders. Hens (n = 120) were randomly allocated into six groups receiving either aerosolised E. coli or vehicle, or intratracheal E. coli or vehicle. Replication of aerosol inoculation was performed on distinct days. Alternating euthanasia time points were predetermined in order to evaluate the progression of the disease. All animals were thoroughly necropsied, and bacteriological samples were collected as well as tissues for histopathology. Birds inoculated with E. coli exhibited clinical signs and developed characteristic gross and histopathological lesions of colibacillosis, including splenic fibrinoid necrosis, folliculitis, polyserositis and impaction of parabronchi with fibrinoheterophilic exudate and necrotic debris, as well as positive in situ localisation of intralesional E. coli by immunohistochemistry. This study presents a successful development of a discriminative colibacillosis model through aerosol inoculation of adult broiler breeders. Gross and histopathological lesions characteristic of colibacillosis were established in two independent experiments.

Klebsiella Aerogenes Infection on the Costochondral Graft of the Nose.

Klebsiella aerogenes is a nosocomial and pathogenic bacterium that causes opportunistic infections including most types of infections. After rhinoplasty, the inserted costochondral graft could be a good material for bacterial growth due to less vascularization and difficult-to-reach antibiotics. The unusual bacterial infection should be considered for preventing poor aesthetic results including graft or implant loss when the surgical site infection is uncontrolled despite proper treatment and administration in aesthetic rhinoplasty surgery. The use of appropriate antibiotics for drug sensitivity may be necessary with bacterial culture tests. In this case, an unusual K. aerogenes infection on the costochondral graft of the nose and related treatment course was reported.

Antimicrobial resistance profiles of Enterobacter cloacae and Klebsiella aerogenes a tertiary hospital in Turkey: A five-years study

Objective: Enterobacter cloacae and Klebsiella aerogenes species have multiple drug resistance and antibiotic resistance is a growing problem regarding to treating infections.
 Objective: The aim of this study was to determine and evaluate the antimicrobial resistance profiles of E. cloacae and K. aerogenes isolated from various clinical samples in our laboratory, retrospectively.
 Material and Methods: Totally 223 patients who applied to Karabuk University Training and Research Hospital microbiology laboratory between October2016-December2020 were included in this study. Conventional methods and automated systems were used for the identification and antibiotic susceptibilities of strains. Antibiotic susceptibility results were evaluated as per the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.
 Results: Total of 223 clinical samples (urine 68.6%, blood 12.6%, endotracheal aspirate 7.2%, wound 4.9%, sputum 3.6%, bronchoalveolar lavage fluid 2.7%, and ear fluid 0.4%) obtained from 223 patients; 119 (53%) females and 104 (47%) females, were analysed. The identified species were E. cloacae (132 strains, 59.2%) and K. aerogenes (91 strains, 40.8%). The Enterobacter cloacae and Klebsiella aerogenes positivity was detected as 30(13.4%) and 20(9.0%) in the samples. The highest resistance was found against cefixime at a rate of 60%; the lowest resistance was against amikacin, meropenem and imipenem ranged between 3% and 4% in both E. cloacae and K. aerogenes strains.
 Conclusions: Amikacin, imipenem and meropenem were the most effective antibiotics against E. cloacae and K. aerogenes. We may prefer TMP-SMX and ciprofloxacin, as oral antibiotic agents in the treatment of E. cloacae/K. aerogenes infections. Amikacin, gentamicin and carbapenems may be the first choice for parenteral antibiotics therapy

Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis.

The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-α deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b+F4/80+ monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing of M. tuberculosis.

MODERN APPROACHES TO THE PREVENTION OF REO-VIRUS BIRD INFECTION

Currently, reo-virus infection causes significant economic damage to industrial poultry worldwide. Losses as a result of the disease consist of: 1) direct losses - death of chickens (5-30 %), increased culling due to lameness, low weight gain (up to 40 %), reduction of carcass categories, reduction of laying by 6-20 %; in breeding farms, a decrease in the sexual activity of poultry is observed, which is the reason for the decrease in fertilization - derivability; 2) indirect losses associated with the cost of eliminating the effects of primary losses, as well as the immune-suppressive effect of reo-viruses, which increase the risk of other infections and inhibit the formation of post-vaccine immunity. Reo-virus has an immune-suppressive effect on the sick bird, which may be the cause of such diseases as small absorption syndrome and syndrome of increased bird death. Small absorption syndrome, which can be caused by reo-virus, is characterized by slowing growth, low feed conversion index and damage to the bones of the bird, which becomes apparent until 2 weeks of age and later. The syndrome of absorption is characterized by an increase in glandular stomach, sometimes with necrosis and signs of catarrhal hemorrhagic enteritis. The incidence is on average 5 to 15 %, but can reach up to 40 %.
 In studying the pathogenesis of reo-virus infection, it was found that the intestine is the main target of the virus, regardless of the method of its introduction. After oral or aerogenic infection, the pathogen enters the bloodstream and, as a result of viremia, is rapidly spread to various organs and tissues. In particular, the virus can be isolated from the intestines, bursa of Fabricius, liver, pancreas, heart, kidneys, joints and tendons. When conducting serological studies in ELISA (test system company IDvet, France), the presence of antibodies in the blood of broilers to reo-virus level ranged from 40-52 days in the range from 1125 to 5138 indicates the circulation of the field virus of reo-virus infection. In the study of broiler sera for 2, 3, 7 days, the cultivation of specific antibodies to reo-virus was not detected. Starting from the 14th day, the mean titer of AO to reo-virus was 1989 and their levels ranged from 3478 to 4825 at 21, 28, 35 and 45 days. 2.3 times (35 days) and 45 days 2.4 times.
 These data indicate the circulation of a field strain of reo-virus infection. It was inserted that at completion of broiler fattening with reo-virus lesion, body weight was lower than the technological norm by 9.8%. When determining specific BP for reo-virus in sera from different age groups of broilers of 11 batches, including from poultry: 9 batches of non-vaccinated against reo-virus infection and 2 batches of vaccinated poultry have determined the number of BPs in serum among the 9 batches received from the unvaccinated parent stock, there is evidence of field strain circulation. The percentage of specific AOs in 2 batches received from parental herds vaccinated against reo-virus infection ranged from 87.5-100, indicating the effectiveness of the vaccination. To control reo-virus infection, serological monitoring in poultry farms should be carried out.

Integrated protection of winter wheat from a complex of harmful causes in european non-chernozem region of the RF

The results of many years of research on the effectiveness of the integrated use of crop protection means and fertilizers with the application of various tillage systems for cultivation of winter wheat of Moskovskaya variety 39 are presented. The studies were conducted in the European nonchernozem soil of Moscow Region on sod-podzolic medium loamy medium-cultivated soil. It was shown that weeds are mainly represented by broadleaved species with an amount of 270 to 370 pcs/ m2. Among pests, cereal aphids and capsid bugs dominate. Among diseases, Helminthosporium and Fusarium root rot (up to 30–40%) and aerogenic infections – brown leaf rust (15-28%) and leaf spot (17-25%) were noted. Studies showed high individual effectiveness in eliminating harmful causes by using appropriate means of protection – seed disinfectants, herbicides, fungicides and insecticides. Weed infestation decreased by 78-85%, root rot development – by 78-81, leaf diseases – by 91-98, pests – by 78-100%. At the same time, the weak effectiveness of the Alto-super fungicide against Septoria and Karate insecticide against wheat thrips was noted. The effect of protective measures on the stored crop was as follows: seed disinfectants – 18%, insecticides – 21, herbicides – 39, fungicides – 22%. The highest economic effect was obtained with the integrated use of plant protection products – up to 1.07 t / ha of grain. At the same time, the quality of grain, content of protein and gluten, and grain class increased. The economic effi ciency of the integrated protection system ranged from 4.7 to 8.1 roubles for each rouble spent. The best result in terms of economic effi ciency was obtained with moldboard tillage and the use of a full dose of NPK90 mineral fertilizers and a full integrated protection scheme.

ИЗЫСКАНИЕ ЭФФЕКТИВНЫХ РЕЖИМОВ И ТЕХНОЛОГИИ ОБЕЗЗАРАЖИВАНИЯ ВОЗДУХА НОВЫМ РЕЦИРКУЛЯТОРОМ В КАМЕРНЫХ И ПРОИЗВОДСТВЕННЫХ ОПЫТАХ

As a result of the research, effective modes and technology of air disinfection by a recirculator of ventilated air after its completion have been developed. It was found that in chamber experiments, air contaminated with microorganisms of the 1st ... 4th resistance group is disinfected by 84.6...99.98% during the operation of the recirculator for 20–45 minutes. In production experiments, when installing a recirculator in a room with a volume of 140 m3 and a mode of 1 hour of operation and 2 hours of break during daylight, bacterial contamination of the air decreases by 73.7%, which is sufficient for the prevention of aerogenic infections. For veterinary practice, the document «Technology of using a recirculator of ventilated air for air disinfection at veterinary surveillance facilities» was developed and approved.

Control of airborne infections of wheat

Leaf-stem infections damage the wheat crop. Puccinia recondite and Blumeria graminis are especially harmful. There were outbreaks of septoriosis and pyrenophoresis (Stagonosopra nodorum, Pyrenophora tritici-repentis) and linear rust (Puccinia graminis). The lack of spring wheat crops and deterioration in the grain quality caused by epiphytoties is 25-50%. An effective method for controlling aerogenic infections is the use of fungicides. Studies on the effectiveness and feasibility of fungicidal protection of wheat against pathogens were carried out in Kurgan region. It is economically feasible to use Bacillus subtilis-based substances to prevent wheat infections. In case of a moderate wheat damage, it is recommended to use tank mixes (1/2 of systemic fungicide + hay-bacillus-based biofungicide). In case of mass development of leaf-stem infections, it is necessary to protect the crops using systemic fungicides if there is primary infection of a lower tier of leaves and weather conditions are favorable for pathogens. The use of fungicides preserved more than 30% of the wheat crops and improved the quality of grain. Profitability of chemical protection options increassed by 20-26 %.

Nosocomial Infection Outbreak with Enterobacter aerogenes at a Neonatal Intensive Care Unit and Its Outcomes

Objective Health care associated infections (HAIs) in the neonatal intensive care unit (NICU) are a significant cause of neonatal morbidity and mortality. Enterobacter aerogenes, a gram-negative bacterium, rarely causes HAI in the pediatric and NICUs. We report the case of a HAI outbreak of E. aerogenes in an NICU and discuss the clinical spectrum and outcome of the affected preterm newborns and successful prevention measures. Materials and Methods A retrospective study was conducted in a level III NICU of Etlik Zubeyde Hanım Women's Health Teaching and Research Hospital. The infants with blood cultures positive for E. aerogenes during the outbreak were enrolled. Perinatal risk factors, laboratory findings, symptoms, treatment, and prognosis were recorded. Clinical applications and prevention measures were identified. Results A preterm infant of 27 weeks of gestation who was diagnosed on the eighth postnatal day was the initial case of the reported outbreak of health care associated E. aerogenes infection. Subsequently, 12 more infants were diagnosed in the next 3 months. Infants' mean gestational age was 27.1 ± 2.3 weeks, and mean birthweight was 902 ± 161 g. The clinical symptoms at presentation were respiratory distress, sclerema, circulatory failure, and shock, which appeared at a mean age of 7.6 ± 5.8 days. Analysis of E. aerogenes strains revealed that all strains were of the same clonal type. Eight patients died in follow-up due to E. aerogenes septicemia during this outbreak. The mean interval between the onset of symptoms and death was 1.5 ± 1 days. Conclusion Outbreaks of health care associated E. aerogenes infection result in a high mortality rate among very low birthweight infants. Awareness of adjustable risk factors and preventive measures to control the outbreak decreases both morbidity and mortality.

PROTECTION OF PLANTS AS A FACTOR OF INFLUENCE ON THE QUALITY OF GRAIN OF WHEAT

The article analyzes data on the effect of fungicidal and herbicidal preparations on grain quality and productivity of spring wheat. Timely and high-quality use of plant protection products from harmful organisms can improve not only the productivity of spring wheat, but often the quality of grain. In the years of mass spread of aerogenic infections, the use of fungicides in wheat crops can increase the protein content of the grain, as the leaves are longer and more productive photosynthesize. Under these conditions, the increase of the content of gluten on the use of systemic multi-component fungicide in the phase of the flag leaf was 3 %, in case of moderate development of disease was 2.4 %. The yield of flour increased by 5-7 %, and in some years there was an improvement in baking evaluation from satisfactory on the control variant to good on the variant with using a system fungicide. Correlation dependence of disease development and gluten content in grain was characterized as very strong and very strong inverse (r=0.88-0.98). In years with the strong development of leaf spots and the defeat of straw linear rust requires double use of fungicides to preserve the crop and grain quality. Long-term tests of post-emergence herbicides have shown that the use of these drugs in the framework of the regulations of their use did not worsen the quality of spring wheat grain, but also a significant stable positive effect on this indicator was not observed.

The C3HeB/FeJ mouse model recapitulates the hallmark of bovine tuberculosis lung lesions following Mycobacterium bovis aerogenous infection

Achieving the control of bovine tuberculosis (bTB) would require the discovery of an efficient combined immunodiagnostic and vaccine strategy. Since in vivo experiments on cattle are not ethically and economically acceptable there is a need for a cost-effective animal model capable of reproducing, as closely as possible, the physiopathology of bTB to (i) better characterize the cellular and molecular features of bTB immunopathogenesis and (ii) screen preclinical vaccine candidates. To develop such a model, we focused on the C3HeB/FeJ Kramnik’s mouse forming hypoxic, encapsulated granulomas with a caseous necrotic center following Mycobacterium tuberculosis infection. Our work represents the first investigation on C3HeB/FeJ interaction with M. bovis, the main agent of bTB. Detailed histopathological analysis of C3HeB/FeJ lung lesions development following aerogenous M. bovis infection unraveled a bimodal evolution of the pathology. The C3HeB/FeJ recapitulated all the hallmarks of classical bovine lung granulomas but also developed, to some extend, lethal necrotic large lesions characterized by high mycobacterial and neutrophil load, and an inefficient collagen-driven lesion encapsulation. Interestingly these rapidly invasive pneumonia lesions, occurring in a constant percentage of the mice, shared all features with some exacerbated lung lesions that we and others have observed in lungs of cattle naturally or experimentally infected with M. bovis. Together, our findings demonstrate the relevance of the C3HeB/FeJ mouse as a comprehensive model to study bTB immunopathology that could be used for further vaccine therapies in the future.

Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis.

A better understanding of the kinetics of accumulated immune cells that are involved in pathophysiology during Mycobacterium tuberculosis (Mtb) infection may help to facilitate the development of vaccines and immunological interventions. However, the kinetics of innate and adaptive cells that are associated with pathogenesis during Mtb infection and their relationship to Mtb virulence are not clearly understood. In this study, we used a mouse model to compare the bacterial burden, inflammation and kinetics of immune cells during aerogenic infection in the lung between laboratory-adapted strains (Mtb H37Rv and H37Ra) and Mtb K strain, a hyper-virulent W-Beijing lineage strain. The Mtb K strain multiplied more than 10- and 3.54-fold more rapidly than H37Ra and H37Rv, respectively, during the early stage of infection (at 28 days post-infection) and resulted in exacerbated lung pathology at 56 to 112 days post-infection. Similar numbers of innate immune cells had infiltrated, regardless of the strain, by 14 days post-infection. High, time-dependent frequencies of F4/80-CD11c+CD11b-Siglec-H+PDCA-1+ plasmacytoid DCs and CD11c-CD11b+Gr-1int cells were observed in the lungs of mice that were infected with the Mtb K strain. Regarding adaptive immunity, Th1 and Th17 T cells that express T-bet and RORγt, respectively, significantly increased in the lungs that were infected with the laboratory-adapted strains, and the population of CD4+CD25+Foxp3+ regulatory T cells was remarkably increased at 112 days post-infection in the lungs of mice that were infected with the K strain. Collectively, our findings indicate that the highly virulent Mtb K strain may trigger the accumulation of pDCs and Gr1intCD11b+ cells with the concomitant down-regulation of the Th1 response and the maintenance of an up-regulated Th2 response without inducing a Th17 response during chronic infection. These results will help to determine which immune system components must be considered for the development of tuberculosis (TB) vaccines and immunological interventions.

In Vivo Evolution of Bacterial Resistance in Two Cases of Enterobacter aerogenes Infections during Treatment with Imipenem.

Infections caused by multidrug resistant (MDR) bacteria are a major concern worldwide. Changes in membrane permeability, including decreased influx and/or increased efflux of antibiotics, are known as key contributors of bacterial MDR. Therefore, it is of critical importance to understand molecular mechanisms that link membrane permeability to MDR in order to design new antimicrobial strategies. In this work, we describe genotype-phenotype correlations in Enterobacter aerogenes, a clinically problematic and antibiotic resistant bacterium. To do this, series of clinical isolates have been periodically collected from two patients during chemotherapy with imipenem. The isolates exhibited different levels of resistance towards multiple classes of antibiotics, consistently with the presence or the absence of porins and efflux pumps. Transport assays were used to characterize membrane permeability defects. Simultaneous genome-wide analysis allowed the identification of putative mutations responsible for MDR. The genome of the imipenem-susceptible isolate G7 was sequenced to closure and used as a reference for comparative genomics. This approach uncovered several loci that were specifically mutated in MDR isolates and whose products are known to control membrane permeability. These were omp35 and omp36, encoding the two major porins; rob, encoding a global AraC-type transcriptional activator; cpxA, phoQ and pmrB, encoding sensor kinases of the CpxRA, PhoPQ and PmrAB two-component regulatory systems, respectively. This report provides a comprehensive analysis of membrane alterations relative to mutational steps in the evolution of MDR of a recognized nosocomial pathogen.