The meta-analysis integrates transcriptomic data from two independent datasets (GSE8732 and GSE84554) to elucidate Mycobacterium tuberculosis (Mtb)'s transcriptional response to iron limitation, a key host defense mechanism. The study identifies a core set of consistently differentially expressed genes (DEGs) critical for Mtb's survival under iron-restricted conditions. Key upregulated genes include those involved in siderophore biosynthesis (mbtA, mbtB, mbtE, mbtI), which are essential for iron acquisition, and components of the ESX secretion system (esxG, esxH, esxR, esxS), linking iron scavenging to virulence. Additionally, PE/PPE family genes (PPE37, PE5), implicated in immune evasion, were consistently upregulated, suggesting their role in host-pathogen interactions during iron scarcity. Conversely, downregulated genes included iron storage proteins (bfrA), regulatory factors (ideR, sigB, rpoC), and metabolic enzymes (aspC, frdA), reflecting a strategic shift away from iron-dependent processes to conserve resources. Temporal analysis revealed a dynamic adaptation process: early-phase responses prioritized iron acquisition, while prolonged starvation induced metabolic restructuring (e.g., upregulation of fadD33, kasB) and stress responses (grpE). The iron-dependent regulator IdeR emerged as a central player, derepressing iron acquisition genes under low iron but also revealing additional regulatory layers. The consistent DEGs across datasets validate their biological significance and highlight potential therapeutic targets, such as siderophore biosynthesis and ESX systems, to disrupt Mtb's adaptation during infection. This study advances insights into Mtb's pathogenicity and survival strategies under host-imposed iron restriction, offering a framework for novel anti-tuberculosis interventions.
The human pathogen Mycobacterium tuberculosis (Mtb) thrives in lipid-rich microenvironments. A strong body of evidence demonstrated that, during infection, Mtb utilizes long-chain fatty acids (LCFA) as a preferred carbon source. However, LCFA also have antimicrobial properties. Mtb must therefore employ mechanisms to utilize LCFA while mitigating their toxicity. Using transposon sequencing (TnSeq), we defined the Mtb LCFA resistome as comprising 38 genes. Surprisingly, LCFA resistance requires diverse metabolic pathways, indicating pleiotropic effects of LCFA on Mtb physiology. We investigated the function of the TnSeq top-hit, the universal stress protein TB15.3, and demonstrate that it participates in a "metabolic brake" mechanism restricting LCFA uptake and catabolism to prevent membrane hyperpolarization. TB15.3 absence caused Mtb to lose viability during chronic infection in mice and in an in vitro caseum model. Our work highlights Mtb LCFA resistance mechanisms as an important host adaptation and a promising target space for drug development.
BACKGROUND: This study aimed to investigate the incidence of latent TB infection (LTBI) and conversion rate among hospital inpatients contacts using an interferon-gamma release assay (IGRA)-based contact tracing strategy. METHODS: We conducted a retrospective study at a 2,700-bed tertiary hospital in Seoul, South Korea. Data from January 2019 to December 2024 were reviewed. Contacts were recommended to undergo IGRA testing at the time of exposure (baseline) and again at ≥6 weeks later after exposure. RESULTS: A total of 109 index cases required contact tracing, yielding 902 contacts, of whom 360 underwent IGRA testing between 1 and 6 months post-exposure (median, 48 days [interquartile range, 25-83]). At baseline, 79 (22%) tested IGRA-positive. Among 133 initially IGRA-negative individuals who underwent serial testing, 18 (14%) demonstrated IGRA conversion. Overall, 97 (27%) were diagnosed with LTBI. Multivariate analysis revealed that age (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.03-1.05; P = 0.002) and exposure in open-plan intensive care unit beds (aOR, 2.09; 95% CI, 1.19-3.70; P = 0.01) were significantly associated with LTBI. CONCLUSIONS: Hospital-based contact investigation identified a substantial burden of latent tuberculosis infection among exposed individuals. IGRA conversion, rather than baseline positivity, may serve as a more reliable indicator of recent transmission in high or intermediate-burden settings, supporting the importance of serial testing in healthcare-associated TB exposure.
With the remarkable success of antiretroviral programmes for the prevention of vertical HIV transmission, there has been a notable reduction in the proportion of children born with HIV and, subsequently, a corresponding increase in the population of children who are HIV-exposed but uninfected (CHEU). There is growing appreciation for the increased risk of childhood morbidity and mortality among CHEU compared with children who are HIV-unexposed, particularly from infectious diseases. Given the high prevalence of tuberculosis in populations with high HIV prevalence, the effect of HIV exposure on tuberculosis is therefore of particular interest. In this Review, we contextualise and reflect on the existing literature for CHEU with regard to prevention, prevalence, and outcomes of tuberculosis infection and tuberculosis disease. In so doing, we identify gaps in reported knowledge on CHEU to guide future research.
BACKGROUND: Several studies have examined host and pathogen genetic influences on tuberculosis (TB) susceptibility separately, but relatively few studied their combined effects. However, host-pathogen interactions or co-evolution may explain the inability to replicate many reported human genetic effects across global populations and provide additional insight into TB risk. In this study, we address such possible interactions by focusing on the outcome of infection with the L4-Uganda M. tuberculosis sub-lineage and human genetic variants as independent variables. This is possible because the L4-Uganda sub-lineage is both restricted to Uganda and nearby locations and is recent there, compared to other more ancestral L4 lineages. METHODS: Our study consisted of 276 culture-confirmed adult TB cases from a long-standing household contact study. We conducted a genome-wide association study, with infection with L4-Uganda versus L4-NonUganda as the outcome. RESULTS: Multiple loci with results suggestive of association (p<10-5) also demonstrated convergent relevant evidence for strain specific infection via: evidence of gene expression in relevant cells and lung tissue, signatures of natural selection, eQTL expression, and CRISPR screens for immunity-related genes. We also replicated previously published host-pathogen interaction effects, demonstrating that effects seen for other sub-lineages were also present for L4-Uganda. CONCLUSIONS: These results provide evidence for host-pathogen co-evolution in TB, consistent with our previous work, and indicate these interactions involve genes highly relevant to the host immune response to Mycobacterium infection.
OBJECTIVES: Liver transplantation is a life-saving treatment for end-stage liver disease and acute liver failure. This study examines infections that develop within 1 year after liver transplantation, their risk factors, and patient prognoses. MATERIALS AND METHODS: This study retrospectively reviewed the follow-up files and hospital computer records of patients who underwent liver transplantation at our hospital between 2010 and 2024. Patients information were recorded. After data analysis, statistical significance was accepted as p < .05. RESULTS: Of the 106 patients included in the study,0000-0002-7491-2710 the mean age at transplantation was 47.61 ± 12.17 (20-67), and 56 (52.8%) were male. The most common indication for transplantation was cryptogenic liver cirrhosis (26.4%). Nineteen (17.9%) patients died within the first 48 hours after transplantation. Of the 87 patients who survived after transplantation, 68 (78.2%) experienced at least 1 episode of infection, resulting in a total of 135 infections. Intra-abdominal infection (28.1%) was the most common post-transplantation infection. In the 1-year post-transplant period, the most common infections were bacterial (57.8% Gram-negative microorganisms) in 71.5% of cases, followed by fungal (16.5%), viral (6.5%), parasitic (5.5%), and M. tuberculosis (0.9%). Klebsiella spp. was the most common bacterial agent in 32 (29.3%) cases, and carbapenem resistance was detected in 64.9%. Enterococcus spp. was the most common Gram-positive microorganism in 12 (11%) cases. The duration of surgical prophylaxis was longer in patients who did not develop infection than in patients who did (p = .014). The length of intensive care unit stays in patients who developed infection was longer than in patients who did not (p = .033). Five patients (8.9%) died due to infection. CONCLUSION: Although bacterial infections are the most common, opportunistic viral, fungal, and parasitic infections can also occur in liver transplant patients. Because these infections can lead to patient death, rapid diagnosis and early initiation of treatment are crucial.
Host-derived biomarkers are high-priority targets for development and could play important roles in diagnosis of various states of () infection and disease, prediction of outcomes, and might guide vaccine and drug regimen evaluation. We discuss the need for priority tuberculosis (TB) biomarkers, including markers of immune sensitization, prediction of progression, diagnosis of asymptomatic and symptomatic TB, including extrapulmonary TB, and treatment monitoring. The focus of the review is on ex vivo transcriptomic and proteomic markers as these are amenable to the development of field-near test formats, which are the most appropriate tests for future incorporation into TB management programs in resource-scarce settings, where the need for new tools is the greatest. The performance of candidate markers is measured against World Health Organization (, www.who.int/publications/i/item/9789240113572)-devised target product profiles, and challenges for harmonized research approaches to secure strong clinical data, coupled with sample repositories, and biomedical resources are discussed.
Tuberculosis (TB), caused by infection with (MTB), represents an important cause of morbidity and mortality worldwide for which an improved vaccine and immunodiagnostics are urgently needed. CD4 and CD8 T cells play an important role in host defense to TB. Definition of the immunodominant antigens recognized by these T cells is critical for improved understanding of the immunobiology of TB and for development of vaccines and diagnostics. Herein, we review antigens and epitopes recognized by classically human leukocyte antigen (HLA) class I- and class II-restricted CD4 and CD8 T cells in humans infected with MTB, as defined using either targeted or genome-wide approaches. We address the extent to which these antigens have been defined as immunodominant, protective, and/or specific to disease stages in humans and, with particular relevance to CD8 T-cell recognition, whether these antigens are displayed by MTB-infected cells.
Our ability to cope with () infection requires activated macrophages to help confer host defense. The extent to which these cells directly eliminate or restrain varies not only within different human populations but also within a given individual at different times following infection and in different lesions. Genetic studies of susceptible people reveal macrophage-activating cytokines like interferon (IFN)-γ and tumor necrosis factor (TNF) are key determinants of protective immunity against tuberculosis. Both cytokines mobilize macrophage effector programs to kill or restrict the bacterium. Among the downstream agents responsible for this inhibition are reactive nitrogen species (RNS) and reactive oxygen species (ROS); lysosomal and autophagic defense; and antimicrobial peptides, metabolites, and metal ion-binding proteins. Together these cell-autonomous effector pathways furnish toxic products or withhold essential micronutrients. It is a testament to the evolutionary fitness of that immune sterilization is often incomplete, although sufficient to ensure that most people infected with this airborne pathogen remain disease-free.
BACKGROUND: We estimated the incidence, viral aetiology and risk factors of acute lower respiratory infection (ALRI) and severe ALRI among community-dwelling older adults at four sites in India. METHODS: Adults ≥60 years were recruited and followed between July 2018 and March 2023. Each week, trained nurses screened all participants for ALRI using modified British Thoracic Society criteria. ALRI was further categorised as severe ALRI if the respiratory rate was >30 breaths per minute or the SPO was <94% or the patient was hospitalised with respiratory symptoms. Combined nasal and throat swabs from ALRI cases were tested for multiple viral pathogens. The incidence of ALRI, severe ALRI and respiratory hospitalisation per 1000 person-years (TPY) was estimated. Adjusted rate ratios (aRR) were calculated by multilevel Poisson regression to identify risk factors for ALRI and severe ALRI. RESULTS: We followed 7240 participants for 19 914 person-years; 59.5% were women. Their mean age was 66.2 years. The incidence of ALRI, severe ALRI and respiratory hospitalisation was 98.0/TPYs, 22.1/TPYs and 12.1/TPYs, respectively. Males (aRR: 1.2), those with body mass index <18.5 kg/m (aRR: 1.6) or ≥30 (aRR: 1.5), coronary artery disease (aRR: 1.5), current or past tuberculosis (aRR: 2.4), chronic respiratory disease (aRR: 5.4) and the use of solid fuel in the household (aRR: 2.0) had higher risk of severe ALRI. Viruses were detected in 16.8% of ALRI cases, influenza (8.8%) was the most detected viral pathogen followed by rhinovirus (2.7%). CONCLUSION: Rates of ALRI and severe ALRI were high; malnutrition, chronic morbidities and the use of solid fuel were important risk factors for severe ALRI.
Researchers report 87% efficacy in phase II trials of new combination therapy targeting drug-resistant TB strains.
Environmental sampling identified previously unknown mycobacterium with potential bioremediation applications.
New AI tool demonstrates 92% accuracy in predicting resistance profiles from genomic sequences.
New Publications
Growth from April
Active Researchers
The Journal of Infectious Diseases published a special issue examining how climate change affects mycobacterium transmission, virulence, and treatment challenges.
Hot TopicNovel diagnostic tool using CRISPR technology achieves detection sensitivity of 10 CFU/mL in clinical samples.
Comprehensive analysis reveals novel antigens for next-generation vaccine development.
Global database reveals geographic patterns in antimicrobial resistance evolution.
Phase I clinical trials show promising results for phage therapy against resistant mycobacterial infections.
Loading personalised statistics...
Help us improve the summary