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Catheter-associated urinary tract infections (CAUTI) are complex infections often involving multi-species bacteria. Escherichia coli is frequently an early coloniser. Subsequent colonisation by Pseudomonas aeruginosa and coexistence mechanisms between the two strains within urethral catheters is not yet fully understood. In this study, metabolic adaptations between co-isolated clinical E. coli and P. aeruginosa strains were investigated. It was found that P. aeruginosa outgrew E. coli in artificial urine medium (AUM), whereas E. coli dominated in culture broth such as Iso-sensitest. No evidence of direct antagonism was observed. Metabolite analyses revealed distinct metabolite patterns indicating cross-feeding and metabolic adaptations. In AUM, stress-response metabolites were elevated. Additionally, E. coli appeared to experience Fe-limitation in AUM, while the same was not observed for P. aeruginosa. The results highlight the influence of nutrient conditions on processes within mixed biofilms.

Introduction: Bacterial colonization of medical devices is promoting hospital-acquired infections leading to worsening patient outcomes and high costs for society. Sequential bacterial colonization of surfaces may provide altered conditions that benefit pathogens.

Methods: In this study we have investigated the interactions between two pairs of clinical isolates collected from patients that were on mechanical ventilation. Two patients were first colonized by Staphylococcus aureus and thereafter Pseudomonas aeruginosa settled. The two P. aeruginosa isolates were weak colonizers in monoculture. We investigated two hypotheses: (1) S. aureus preconditions material surfaces, facilitating adhesion of later colonizers. (2) S. aureus provides an altered nutrient environment promoting the growth and settlement of other bacteria.

Results: Surface preconditioning did not seem to enhance colonization of P. aeruginosa. However, bacterial growth, biofilm formation, ratio of colony forming units, and metabolic profiles were influenced by co-cultivation. The effects varied depending on nutrient content in the medium.

Discussion: In general, co-cultures appeared to benefit clinical isolates to a higher degree, compared to reference strains. The results indicate that differences in airway microenvironment between patients may have a large effect on the infection process and which pathogens that persist.

Introduction: Tuberculosis (TB) treatment typically involves a tailored combination of four antibiotics based on the drug resistance profile of the infecting strain. The increasing drug resistance of Mycobacterium tuberculosis (Mtb) requires the development of novel antibiotics to ensure effective treatment regimens. Gallium (Ga) is being explored as a repurposed drug against TB due to its ability to inhibit Mtb growth and disrupt iron metabolism. Given the potential interactions between Ga and established antibiotics, we investigated how a combination of Ga with levofloxacin (Lfx) or linezolid (Lzd) affects the growth and metabolome of a multidrug-resistant (MDR) Mtb clinical strain.

Methods: Mtb was cultured using a BACTEC 960 system with concentrations of Ga ranging from 125 to 1,000 μM and with 250 to 500 μM of Ga combined with 0.125 mg/L of Lfx or Lzd. For metabolome analysis, the antibacterials were used at concentrations that inhibited the growth of bacteria without causing cell death. Metabolites were extracted from Mtb cells and analyzed using chromatography-mass spectrometry.

Results: The MDR Mtb strain exhibited a dose-dependent response to Ga. Notably, the enhancement in growth inhibition was statistically significant for the Ga/Lfx combination compared to Ga alone, while no such significance was observed for Ga/Lzd. Moreover, exposure to Ga/Lfx or Ga/Lzd resulted in distinct metabolite profiles. Ga treatment increased the level of aconitate, fumarate, and glucose in the cells, suggesting the inhibition of iron-dependent aconitase and fumarate hydratase, as well as disruption of the pentose phosphate pathway. The levels of glucose, succinic acid, citric acid, and hexadecanoic acid followed a similar pattern in cells exposed to Ga and Ga/Lfx at 500 μM Ga but exhibited different trends at 250 μM Ga.

Discussion: In the presence of Lfx, the Mtb metabolome changes induced by Ga are more pronounced compared to those observed with Lzd. Lfx affects nucleic acids and transcription, which may enhance Ga-dependent growth inhibition by preventing the metabolic redirection that bacteria typically use to bypass iron-dependent enzymes.

Background: The ethiology behind lymphadenopathy syndrome (LAP) in children who frequently present with acute respiratory infections is not fully understood. Purpose – to study the characteristics of immune system in children who frequently present with lymphadenopathy syndrome.

Materials and methods: An immunological evaluation was conducted in four groups children aged 9–16 years. The first (main) group, (n=40), included those who frequently (6–8 times/year) presented with acute respiratory infections, recurrent bronchitis, and lymphadenopathy syndrome. The second group (comparison group (n=40)) those who also experienced acute respiratory infections and recurrent bronchitis 6–8 times/year but without, lymphadenopathy syndrome. The third group (comparison group (n=40)) presented with acute respiratory infections and acute bronchitis but did not have lymphadenopathy syndrome and were not categorized as frequently ill. The fourth (control (n=40)) group consisted of 30 healthy children of the same age. Local immunity was evaluated by measuring lysozyme, monomeric and dimeric IgA, IgG, and defensins concentration in saliva. Subpopulation composition of blood lymphocytes were studied by flow laser cytometry using specific monoclonal antibodies. The phagocytic activity of blood leukocytes was assessed using the thick drop method, based on their ability to ingest S. aureus.

Results: The obtained data indicate that acute respiratory infections in children of groups 1 and 2 occur against the background of reduced concentrations and activity of key humoral factors of local immunity: lysozyme, defensins, and sIgA. However, during the acute phase of the illness in these groups, a slight increase in IgG secretion in saliva was observed. After recovery, the levels of lysozyme, defensins, and sIgA did not return to normal, remaining significantly lower (p<0.05) compared to healthy subjects. In contrast, in group 3, the development of acute respiratory infections is accompanied by the activation of local protective factors. An increase in the concentration of monomeric and dimeric IgA, defensins, and lysozyme is observed in the secretion. After recovery, the levels of these factors in children of group 3 return to physiological norms.

Conclusions: Children who frequently suffer from acute respiratory infections with lymphadenopathy syndrome exhibit a combination of reduced overall immunoreactivity of the body and hyperactivity of certain lymphocyte subpopulations. For children with lymphadenopathy syndrome, both during the acute phase of the disease and after recovery, an increase in the levels of activated T-and B-lymphocytes with high cytokine-producing potential, as well as an increase in the polyclonal proliferative activity of lymphocytes, is characteristic.

Background: European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.

Aim: We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.

Methods: The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.

Results: Data on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.

Conclusions: Country of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

The spread of COVID-19 in countries with high and medium incidence of tuberculosis has led to an increased risk of COVID-19 and tuberculosis co-infection, introducing new diagnostic and therapeutic challenges for the clinician. Hereby we describe a first case where tuberculosis and COVID-19 were diagnosed concomitantly in a Russian patient with pneumothorax. We discuss the challenges associated with the diagnosis and treatment of tuberculosis during the COVID-19 pandemic.

Pharmaceutical substances present at low concentrations in the environment may cause effects on biological systems such as microbial consortia living on solid riverbed substrates. These consortia are an important part of the river ecosystem as they form part of the food chain. This case study aims to contribute to an increased understanding of how low levels of pharmaceuticals in freshwater streams may influence sessile bacterial consortia. An important point source for pharmaceutical release into the environment is treated household sewage water. In order to investigate what types of effects may occur, we collected water samples as well as riverbed substrates from a small stream in the south of Sweden, Knivstaån, upstream and downstream from a sewage treatment plant (STP). Data from these samples formed the base of this case study where we investigated both the presence of pharmaceuticals in the water and bacterial composition on riverbed substrates. In the water downstream from the STP, 19 different pharmaceuticals were detected at levels below 800 ng/dm3. The microbial composition was obtained from sequencing 16S rRNA genes directly from substrates as well as from cultivated isolates. The cultivated strains showed reduced species variability compared with the data obtained directly from the substrates. No systematic differences were observed following the sampling season. However, differences could be seen between samples upstream and downstream from the STP effluent. We further observed large similarities in bacterial composition on natural stones compared to sterile stones introduced into the river approximately two months prior to sampling, giving indications for future sampling methodology of biofilms.

1. With accelerated land conversion and global heating at northern latitudes, it becomes crucial to understand, how life histories of animals in extreme environments adapt to these changes. Animals may either adapt by adjusting foraging behavior or through physiological responses, including adjusting their energy metabolism or both. Until now, it has been difficult to study such adaptations in free‐ranging animals due to methodological constraints that prevent extensive spatiotemporal coverage of ecological and physiological data.

2. Through a novel approach of combining DNA‐metabarcoding and nuclear magnetic resonance (NMR)‐based metabolomics, we aim to elucidate the links between diets and metabolism in Scandinavian moose Alces alces over three biogeographic zones using a unique dataset of 265 marked individuals.

3. Based on 17 diet items, we identified four different classes of diet types that match browse species availability in respective ecoregions in northern Sweden. Individuals in the boreal zone consumed predominantly pine and had the least diverse diets, while individuals with highest diet diversity occurred in the coastal areas. Males exhibited lower average diet diversity than females.

4. We identified several molecular markers indicating metabolic constraints linked to diet constraints in terms of food availability during winter. While animals consuming pine had higher lipid, phospocholine, and glycerophosphocholine concentrations in their serum than other diet types, birch‐ and willow/aspen‐rich diets exhibit elevated concentrations of several amino acids. The individuals with highest diet diversity had increased levels of ketone bodies, indicating extensive periods of starvation for these individuals.

5. Our results show how the adaptive capacity of moose at the eco‐physiological level varies over a large eco‐geographic scale and how it responds to land use pressures. In light of extensive ongoing climate and land use changes, these findings pave the way for future scenario building for animal adaptive capacity.

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is an emerging threat to TB control in Ukraine, a country with the third highest XDR TB burden globally. We used whole-genome sequencing of a convenience sample to identify bacterial genetic and patient-related factors associated with MDR/XDR TB in this country. MDR/XDR TB was associated with 3 distinct Mycobacterium tuberculosis complex lineage 2 (Beijing) clades, Europe/Russia W148 outbreak, Central Asia outbreak, and Ukraine outbreak, which comprised 68.9% of all MDR/XDR TB strains from southern Ukraine. MDR/XDR TB was also associated with previous treatment for TB and urban residence. The circulation of Beijing outbreak strains harboring broad drug resistance, coupled with constraints in drug supply and limited availability of phenotypic drug susceptibility testing, needs to be considered when new TB management strategies are implemented in Ukraine.