Article
Immunology
Karin Hjort, Pontus Juren, Juan Carlos Toro, Sven Hoffner, Dan Andersson, Linus Sandegren
Summary: Whole-genome sequencing of Mycobacterium tuberculosis from a single patient over 9 years of disease and treatment revealed that antibiotic treatment was the main driver of sequence evolution, leading to stepwise accumulation of resistance mutations to various antibiotics. The study highlighted the dynamic nature of M. tuberculosis infection, population structure, and resistance evolution, emphasizing the importance of rapid antibiotic susceptibility tests in combating this pathogen.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Pharmacology & Pharmacy
Sha Diao, Zheng Liu, Dan Liu, Xiao Cheng, Linan Zeng, Xue-Feng Jiao, Zhe Chen, Xiaofeng Ni, Siyi He, Bin Wu, Deying Kang, Chaomin Wan, Rongsheng Zhao, Huiqing Wang, Lingli Zhang
Summary: Compared with the TB-PPD test, the EC test is more cost-effective for the diagnosis of M. tuberculosis infection in the long term, according to our study.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Microbiology
Catherine Shelton, Matthew McNeil, Renee Allen, Lindsay Flint, Dara Russell, Bryan Berube, Aaron Korkegian, Yulia Ovechkina, Tanya Parish
Summary: By studying the mutations in specific genes of Mycobacterium tuberculosis, we found that triazolopyrimidines can interact with these genes and confer resistance to the bacteria. These compounds deplete intracellular ATP levels and exhibit activity against intracellular bacteria, but have no effect on human mitochondrial respiration.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Shashikant Srivastava, Tawanda Gumbo, Tania Thomas
Summary: Cefazolin-avibactam combination has shown efficacy against MDR-TB and drug susceptible TB strains in children through PK/PD principles. The optimal dosing strategy was determined based on age-specific CFR and Mtb susceptibility breakpoint, highlighting the potential of repurposing cefazolin for pediatric TB treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Immunology
Cheldon Ann Alcantara, Ira Glassman, Kevin H. Nguyen, Arpitha Parthasarathy, Vishwanath Venketaraman
Summary: Mycobacterium tuberculosis (M. tb) remains a major cause of death in developing countries. The BCG vaccine is widely used in developing countries but its efficacy is still uncertain. Neutrophils play a crucial role in the immune response against M. tb, promoting clearance of the bacteria and regulating the inflammatory response. This review highlights the role of neutrophils during M. tb infection and emphasizes the need for more research on effective vaccination.
Article
Public, Environmental & Occupational Health
Zheng Liu, Sha Diao, Linan Zeng, Dan Liu, Xuefeng Jiao, Zhe Chen, Xiao Cheng, Xiaofeng Ni, Siyi He, Bin Wu, Deying Kang, Chaomin Wan, Rongsheng Zhao, Huiqing Wang, Lingli Zhang
Summary: This study aimed to estimate the cost-utility and cost-effectiveness of recombinant Mycobacterium tuberculosis fusion protein (EC) and tuberculin pure protein derivative (TB-PPD) for the diagnosis of Mycobacterium tuberculosis infection in the Chinese population. The results showed that, compared with TB-PPD, EC was a cost-utility and cost-effective intervention in the short term.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Immunology
Wenxi Xu, Laura M. Snell, Mengdi Guo, Giselle Boukhaled, Bethany L. Macleod, Ming Li, Michael Tullius, Cynthia J. Guidos, Ming-Sound Tsao, Maziar Divangahi, Marcus A. Horwitz, Jun Liu, David G. Brooks
Summary: Chronic viral infections exacerbate the severity of Mycobacterium tuberculosis (Mtb) coinfection by increasing Mtb burden, disrupting immune surveillance, and worsening disease mortality. The study demonstrates the impact of viral infections on coinfection and highlights the mechanisms involved in disease progression.
Article
Microbiology
Denis Lagutkin, Anna Panova, Anatoly Vinokurov, Alexandra Gracheva, Anastasia Samoilova, Irina Vasilyeva
Summary: This study examined the variants associated with drug resistance in Mycobacterium tuberculosis (MTB) and the emergence of polymorphisms in MTB genomes after anti-tuberculosis treatment. The results revealed significant associations between specific genes and drug-resistant phenotypes, as well as different patterns of intra-host evolution and lineage-specific polymorphisms in post-treatment isolates. The authors propose that one specific insertion within a gene may play a role in cell wall biosynthesis and contribute to a compensatory mechanism in response to treatment.
Article
Multidisciplinary Sciences
Manse Kim, Claire E. Johnson, Alan A. Schmalstig, Ayano Annis, Sarah E. Wessel, Brian Van Horn, Amanda Schauer, Agata A. Exner, Jason E. Stout, Angela Wahl, Miriam Braunstein, J. Victor Garcia, Martina Kovarova
Summary: This study develops a long-acting delivery system for the anti-tuberculosis drug rifabutin, which is made of biodegradable polymers and biocompatible solvents. The formulation shows high drug load and sustained drug release, and demonstrates translational potential in animal models.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Jees Sebastian, Anooja Thomas, Carly Levine, Riju Shrestha, Shawn Levy, Hassan Safi, Sri Ram Pentakota, Pradeep Kumar, David Alland
Summary: Tuberculosis requires continued treatment for months to achieve a durable cure. A study identified small hidden subpopulations of Mycobacterium tuberculosis that repeatedly enter a state of drug tolerance and have a predisposition to develop drug resistance. These difficult-to-eliminate subpopulations may explain why tuberculosis treatment requires extended regimens. The findings provide opportunities for genetic and therapeutic approaches to develop shorter and more effective tuberculosis treatments.
Article
Immunology
Christina M. Mingora, Wendy Bullington, Paige E. Faasuamalie, Adrah Levin, Gabriella Porter, Ryan Stadnick, Cara D. Varley, Doreen Addrizzo-Harris, Charles L. Daley, Kenneth N. Olivier, Kevin L. Winthrop, Susan E. Dorman, Patrick A. Flume
Summary: This study reports on the clinical experience with omadacycline for the treatment of Mycobacterium abscessus infections at five large nontuberculous mycobacterial disease clinics across the United States, providing data on the long-term safety and tolerability of the drug, and indicating its effectiveness in treating M abscessus infections.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Microbiology
Amit Kumar Singh, Rutuja Gangakhedkar, Hemant Singh Thakur, Sunil Kumar Raman, Shripad A. Patil, Vikas Jain
Summary: To combat drug-resistant Mycobacterium tuberculosis, alternative therapeutics are essential. Mycobacteriophages are efficient therapeutics due to their ability to infect and kill mycobacteria, including M. tuberculosis. In this study, we exploited the mycolyl-arabinogalactan esterase property of LysB encoded from mycobacteriophage D29. This research is novel as it targets multi-drug-resistant pathogenic strains of M. tuberculosis with LysB and examines the combination of anti-TB drugs and LysB. By externally administering LysB, its remarkable lytic activity overcomes the difficulty of entering the complex cell envelope of mycobacteria. Targeting intracellular M. tuberculosis with LysB and its non-toxicity to macrophages advance the development of LysB as a drug, and interaction studies with rifampicin and isoniazid help form a new treatment regimen against tuberculosis.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Mariana Herrera, Yoav Keynan, Lucelly Lopez, Diana Marin, Lazaro Velez, Paul J. McLaren, Zulma Vanessa Rueda
Summary: We studied the immune changes in newly acquired tuberculosis infection in a population deprived of liberty in Colombian prisons. We found differences in immune levels between individuals with new tuberculosis infection and those incarcerated for short and long periods of time. Certain cytokines/chemokines were associated with new tuberculosis infection and tuberculosis disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Yiwang Chen, Lecai Ji, Qingyun Liu, Jinli Li, Chuangyue Hong, Qi Jiang, Mingyu Gan, Howard E. Takiff, Weiye Yu, Weiguo Tan, Qian Gao
Summary: The study found that tuberculosis heteroresistance is common and persistent in patients with multidrug-resistant tuberculosis, potentially affecting the success of their treatment regimens.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Immunology
Amala Bhagwat, Aditi Deshpande, Tanya Parish
Summary: This article discusses various approaches and strategies to address drug resistance in tuberculosis, including developing new drugs or drug combinations, improving the efficacy of existing drugs, and understanding the importance of resistance mechanisms and cross-resistance.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Karin Hjort, Pontus Juren, Juan Carlos Toro, Sven Hoffner, Dan Andersson, Linus Sandegren
Summary: Whole-genome sequencing of Mycobacterium tuberculosis from a single patient over 9 years of disease and treatment revealed that antibiotic treatment was the main driver of sequence evolution, leading to stepwise accumulation of resistance mutations to various antibiotics. The study highlighted the dynamic nature of M. tuberculosis infection, population structure, and resistance evolution, emphasizing the importance of rapid antibiotic susceptibility tests in combating this pathogen.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Genetics & Heredity
Michael Knopp, Arianne M. Babina, Jonina S. Gudmundsdottir, Martin Douglass, M. Stephen Trent, Dan Andersson
Summary: Random sequences can generate novel antibiotic resistance determinants de novo, which act via specific peptide-protein interactions in the transmembrane domain. These peptides may potentially evolve as bona fide resistance determinants in natura.
Article
Microbiology
Roderich Roemhild, Dan I. Andersson
Article
Multidisciplinary Sciences
Komal Umashankar Rao, Domhnall Iain Henderson, Nitya Krishnan, Manoj Puthia, Izabela Glegola-Madejska, Lena Brive, Fanny Bjarnemark, Anna Millqvist Fureby, Karin Hjort, Dan I. Andersson, Erik Tenland, Erik Sturegard, Brian D. Robertson, Gabriela Godaly
Summary: A fungal peptide was found to effectively reduce tuberculosis load and synergize with current TB drugs. The peptide remained stable in circulation and showed efficacy against drug-resistant bacteria.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Xiaohu Guo, Annika Soderholm, Sandesh P. Kanchugal, Geir Isaksen, Omar Warsi, Ulrich Eckhard, Silvia Triguis, Adolf Gogoll, Jon Jerlstrom-Hultqvist, Johan Aqvist, Dan Andersson, Maria Selmer
Summary: Researchers have discovered three new SAMases with barely detectable similarity to T3 SAMase from environmental phages, which share the same structure and reaction mechanism as T3 SAMase.
Article
Infectious Diseases
Jessica Howard-Anderson, Michelle Davis, Alexander M. Page, Chris W. Bower, Gillian Smith, Jesse T. Jacob, Dan Andersson, David S. Weiss, Sarah W. Satola
Summary: This study investigated the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and its association with clinical outcomes. The results showed that colistin heteroresistance was present in up to 26% of CRPA patients, but it did not have a significant impact on 90-day mortality.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Immunology
Greta Zaborskyte, Erik Wistrand-Yuen, Karin Hjort, Dan I. Andersson, Linus Sandegren
Summary: Medical device-related biofilms are a major cause of hospital-acquired infections. The 3D-printed device (FlexiPeg) presented in this study is a robust and easy-to-use tool for studying biofilms, with versatile applications.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Food Science & Technology
Konstantinos Koutsoumanis, Ana Allende, Avelino Alvarez-Ordonez, Declan Bolton, Sara Bover-Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Giuseppe Ru, Marion Simmons, Panagiotis Skandamis, Elisabetta Suffredini, Dan Andersson, Vasileios Bampidis, Johan Bengtsson-Palme, Damien Bouchard, Aude Ferran, Maryline Kouba, Secundino Lopez Puente, Marta Lopez-Alonso, Soren Saxmose Nielsen, Alena Pechova, Mariana Petkova, Sebastien Girault, Alessandro Broglia, Beatriz Guerra, Matteo Lorenzo Innocenti, Ernesto Liebana, Gloria Lopez-Galvez, Paola Manini, Pietro Stella, Luisa Peixe
Summary: The EFSA collaborated with the EMA to assess specific concentrations of amoxicillin and penicillin V in non-target feed for food-producing animals. The study aimed to understand the effects on bacterial resistance and growth promotion. New assessment models were recommended for addressing antimicrobial resistance, along with the need for further data to fill the gaps in calculations.
Article
Food Science & Technology
Ana Allende, Konstantinos Koutsoumanis, Ana Allende, Avelino Alvarez-Ordonez, Declan Bolton, Sara Bover-Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Giuseppe Ru, Marion Simmons, Panagiotis Skandamis, Elisabetta Suffredini, Dan Andersson, Vasileios Bampidis, Johan Bengtsson-Palme, Damien Bouchard, Aude Ferran, Maryline Kouba, Secundino Lopez Puente, Marta Lopez-Alonso, Soren Saxmose Nielsen, Alena Pechova, Mariana Petkova, Sebastien Girault, Alessandro Broglia, Beatriz Guerra, Matteo Lorenzo Innocenti, Ernesto Liebana, Gloria Lopez-Galvez, Paola Manini, Pietro Stella, Luisa Peixe
Summary: The European Food Safety Authority and the European Medicines Agency collaborated to assess the effects of antibiotic concentrations in feed on antimicrobial resistance and growth promotion. Due to data gaps, assessments for some antibiotics could not be completed, and further studies are recommended to fill these gaps.
Article
Food Science & Technology
Konstantinos Koutsoumanis, Ana Allende, Avelino Alvarez-Ordonez, Declan Bolton, Sara Bover-Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Lieve Herman, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Giuseppe Ru, Marion Simmons, Panagiotis Skandamis, Elisabetta Suffredini, Dan Andersson, Vasileios Bampidis, Johan Bengtsson-Palme, Damien Bouchard, Aude Ferran, Maryline Kouba, Secundino Lopez Puente, Marta Lopez-Alonso, Soren Saxmose Nielsen, Alena Pechova, Mariana Petkova, Sebastien Girault, Alessandro Broglia, Beatriz Guerra, Matteo Lorenzo Innocenti, Ernesto Liebana, Gloria Lopez-Galvez, Paola Manini, Pietro Stella, Luisa Peixe
Summary: EFSA collaborated with EMA to assess the specific concentrations of lincomycin in non-target feed for their effect on resistance and growth promotion. However, due to data gaps, the assessment could not be concluded. Further studies are recommended to fill the data gaps.
Review
Microbiology
Roderich Roemhild, Tobias Bollenbach, Dan I. Andersson
Summary: This review discusses the importance of using combination antibiotics to enhance treatment efficacy and combat resistance evolution. While several promising strategies have been proposed, a deeper understanding of the physiological responses and genetic mechanisms underlying antibiotic interactions and their clinical applicability is still lacking.
NATURE REVIEWS MICROBIOLOGY
(2022)
Article
Immunology
Po-Cheng Tang, Olle Eriksson, Josefin Sjogren, Nikos Fatsis-Kavalopoulos, Johan Kreuger, Dan I. Andersson
Summary: Biofilms are a crucial mode of growth for bacteria, but how antibiotic resistance emerges and is selected in biofilms is poorly understood. This study developed and validated a microfluidic chip (Brimor) for studying the dynamics of antibiotic-resistant bacteria in biofilms. The chip was found to be easy to use and a relevant model for studying the selection of antibiotic resistance in bacterial biofilms, providing valuable insights into this area of research.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Karin Hjort, Elin Fermer, Po-Cheng Tang, Dan I. Andersson
Summary: The use and misuse of antibiotics have led to the selection of difficult-to-treat resistant bacteria. This study compared the selection of antibiotic-resistant E. coli strains during planktonic and biofilm growth. The results showed that resistant mutants were selected at sub-minimal inhibitory concentrations (MICs) in both growth conditions, emphasizing the significance of low antibiotic concentrations in driving the emergence and enrichment of resistant bacteria.
Article
Biology
Arianne M. Babina, Serhiy Surkov, Weihua Ye, Jon Jerlstrom-Hultqvist, Marten Larsson, Erik Holmqvist, Per Jemth, Dan Andersson, Michael Knopp
Summary: The origins and evolution of small proteins with diverse physiological roles remain unclear. Recent genomic sequence analyses suggest that new functions encoded by small open reading frames (sORFs) may emerge de novo from noncoding sequences. This study shows that randomly generated sORFs can rescue Escherichia coli cells by upregulating hisB expression and that they bind to the 5' end regulatory region of the his operon mRNA, promoting structural rearrangements of the RNA for increased hisB expression. This provides experimental evidence that small proteins with selective benefits can originate from the expression of nonfunctional sequences.
Article
Biology
Ramith R. Nair, Dan I. Andersson
Summary: The dynamics of nitrofurantoin resistance selection in Escherichia coli is significantly affected by interspecies interactions with Bacillus subtilis. The presence of B. subtilis slows down the selection for resistant E. coli mutants by producing extracellular compounds, particularly the YydF peptide. This study highlights the importance of considering interspecies interactions in understanding and predicting the evolution of antibiotic resistance.
COMMUNICATIONS BIOLOGY
(2023)