Article
Microbiology
Vidar Sorum, Emma L. Oynes, Anna S. Moller, Klaus Harms, Orjan Samuelsen, Nicole L. Podnecky, Pal J. Johnsen
Summary: This study investigates the stability of collateral networks in ciprofloxacin-resistant Escherichia coli strains. The results show that the collateral effects caused by resistance development are not stable, complicating the general applicability and clinical implementation of collateral effects in treatment strategies.
Article
Microbiology
Richard C. Allen, Katia R. Pfrunder-Cardozo, Alex R. Hall
Summary: The study found that local environmental conditions (such as pH, temperature, and bile salts) can influence collateral sensitivity of antibiotics against bacteria, potentially by promoting different sets of mutants during resistance evolution or modifying the expression of collateral effects for individual mutants.
Article
Multidisciplinary Sciences
Helen S. Mueller, Colin E. Fowler, Simona Dalin, Enrico Moiso, Tee Udomlumleart, Salil Garg, Michael T. Hemann, Jacqueline A. Lees
Summary: Epigenetic regulators are crucial in cancer treatment, but resistance mechanisms to their inhibition are not well understood. A study on PRMT5 inhibitors in lung adenocarcinoma cell lines revealed a drug-induced transcriptional switch leading to rapid resistance. The resistant state, stabilized across LUAD variants, also showed vulnerabilities to other chemotherapeutics like paclitaxel, due to the presence of STMN2. This gene was found to be essential for both PRMT5 inhibition resistance and sensitivity to paclitaxel, highlighting a potential therapeutic combination for cancer treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Adam G. Stewart, Michael J. Satlin, Sanmarie Schlebusch, Burcu Isler, Brian M. Forde, David L. Paterson, Patrick N. A. Harris
Summary: Despite the widespread belief that antibiotic use is the primary cause of antimicrobial resistance and disruption of the human microbiome, our understanding of the specific effects of antibiotics on the microbiome is still limited. Detecting associations between different antibiotics and specific AMR burdens is currently inconsistent. Utilizing various microbiome analysis tools and conducting microbiome analysis in antibiotic clinical trials could significantly enhance antibiotic development and clinical decision-making.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Nurseda Danisik, Kubra Celikbas Yilmaz, Ahmet Acar
Summary: This study investigated the mechanism of drug resistance in colorectal cancer cell lines and identified effective second-line drugs using barcoding technology. Results showed the presence of polyclonal evolution and de novo mutations in drug resistance, and collateral drug testing revealed a number of effective drugs.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Microbiology
Sara Hernando-Amado, Carla Lopez-Causape, Pablo Laborda, Fernando Sanz-Garcia, Antonio Oliver, Jose Luis Martinez
Summary: Collateral sensitivity (CS) is an evolutionary trade-off where resistance to one antibiotic leads to increased susceptibility to another. This study analyzed the robustness of CS in clinical strains of Pseudomonas aeruginosa, identifying a robust CS pattern associated with short-term evolution in the presence of ciprofloxacin. The findings suggest that identification of robust CS patterns can form the basis for developing evolutionary strategies to tackle bacterial infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Automation & Control Systems
Josephine N. A. Tetteh, Sorin Olaru, Hans Crauel, Esteban A. A. Hernandez-Vargas
Summary: Drug resistant pathogens pose a global public health threat and their control is a challenging task. A new health paradigm called sequential use of drugs has been proposed, where resistance to one drug leads to sensitivity to another drug, known as collateral sensitivity. Tailoring the order and time of drug cycling to the pathogen population in the host is crucial. Through abstracting mutation networks of collateral sensitivity based on switched systems, this study explores the control theoretical aspects and implications of collateral sensitivity on the eradication of drug-resistant pathogens. Numerical simulations demonstrate the potential of this approach to mitigate drug resistance or even eradicate pathogenic populations.
INTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL
(2023)
Article
Multidisciplinary Sciences
Sara Hernando-Amado, Pablo Laborda, Jose Ramon Valverde, Jose Luis Martinez
Summary: Collateral sensitivity, a trade-off in evolution where resistance to one antibiotic leads to increased susceptibility to another, can be utilized in designing evolutionary-based approaches for treating bacterial infections. This study investigates the conservation of collateral sensitivity in different antibiotic-resistant mutants, and suggests alternating certain antibiotics as an effective strategy to eliminate these mutants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Simen Fredriksen, Stef de Warle, Peter van Baarlen, Jos Boekhorst, Jerry M. Wells
Summary: This study re-analyzed human gut microbiome data from 26 case-control studies and found that diseases commonly treated with antibiotics, such as cystic fibrosis and diarrhea, are associated with significantly elevated antibiotic resistance gene (ARG) abundances in patient microbiomes compared to controls. The association between disease and the resistome exists even in the absence of large taxonomic differences. A trend for increased ARG abundance was also found in cases from some studies on diseases that are not treated with antibiotics, such as colorectal cancer.
Review
Chemistry, Multidisciplinary
Matthew D. Surette, Peter Spanogiannopoulos, Gerard D. Wright
Summary: Rifamycin antibiotics, including rifampin, rifabutin, and rifapentine, are derived from natural rifamycins and primarily used to treat mycobacterial infections such as tuberculosis. These antibiotics inhibit bacterial RNA polymerase by binding to the beta-subunit, leading to cell death. Resistance to rifamycin antibiotics mainly arises from point mutations in RNA polymerase among clinical strains, while environmental mycobacteria and actinomycetes show a richer and diverse rifamycin resistome with various enzymatic mechanisms.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Engineering, Environmental
Chunxia Jiang, Zelong Zhao, Dong Zhu, Xiong Pan, Yuyi Yang
Summary: This study analyzed the occurrence and distribution of antibiotic resistance genes (ARGs) in different environmental media of the Yangtze River using metagenomics. Core resistome dominated by multidrug resistance genes was found in all samples, while rare resistome dominated by various resistance genes was more prevalent in plasmids. Specific bacteria were identified as hosts for both core and rare resistomes, with high clinical concern ARGs found in the rare resistome. Particle-associated environment provided the most ideal conditions for resistome hosts. This study provided insights into the genetic locations of ARGs and the community assembly mechanisms of ARG hosts in freshwater environments.
Article
Microbiology
Mari C. Rodriguez de Evgrafov, Marius Faza, Konstantinos Asimakopoulos, Morten O. A. Sommer
Summary: The study identified universal cross-resistance and global collateral sensitivity relationships among evolved bacterial lineages, along with drug-dependent divergent and conserved evolutionary trajectories among pathogens. These findings suggest that collateral responses may be preserved across species, which could contribute to the development of treatment strategies to address antibiotic resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Kihyun Lee, Sebastien Raguideau, Kimmo Siren, Francesco Asnicar, Fabio Cumbo, Falk Hildebrand, Nicola Segata, Chang-Jun Cha, Christopher Quince
Summary: The authors investigate the population-level impact of antimicrobial resistance genes (ARGs). By analyzing 8972 metagenomes and 3096 gut microbiomes from healthy individuals not taking antibiotics, they find significant correlations between the total ARG abundance and diversity and per capita antibiotic usage rates across ten countries spanning three continents. Using a collection of 154,723 human-associated metagenome assembled genomes (MAGs), they link these ARGs to microbial taxa and detect horizontal gene transfer.
NATURE COMMUNICATIONS
(2023)
Article
Infectious Diseases
Jakob J. Malin, Christian J. H. von Wintersdorff, John Penders, Paul H. M. Savelkoul, Petra F. G. Wolffs
Summary: This study investigated the longitudinal fluctuations in prevalent antimicrobial resistance genes (ARGs) in non-travelling healthy volunteers and found that the abundance changes of prevalent ARGs were independent of travel behavior.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Microbiology
Hua-le Chen, Yan Jiang, Mei-Mei Li, Yao Sun, Jian-Ming Cao, Cui Zhou, Xiao-Xiao Zhang, Yue Qu, Tie-Li Zhou
Summary: This study investigated the acquisition of collateral hypersensitivity by carbapenem-resistant Klebsiella pneumoniae under tigecycline induction. The results showed that while developing tigecycline resistance, stable hypersensitivities to aminoglycosides and other antibiotics were noticed, which might be caused by the loss of an antimicrobial resistance plasmid. This study suggested the rationalized combination of tigecycline with aminoglycosides for the treatment of CRKP infections.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Pablo Laborda, Jose L. Martinez, Sara Hernando-Amado
Summary: This study reveals a robust pattern of collateral sensitivity to fosfomycin in Pseudomonas aeruginosa antibiotic-resistant mutants, characterized by reduced expression of genes related to peptidoglycan synthesis preservation. Understanding these molecular mechanisms could provide valuable information for designing evolution-based strategies to treat bacterial infections.
MICROBIAL BIOTECHNOLOGY
(2022)
Article
Infectious Diseases
Andres Ceballos-Garzon, Lucia Monteoliva, Concha Gil, Carlos Alvarez-Moreno, Nelson E. Vega-Vela, David M. Engelthaler, Jolene Bowers, Patrice Le Pape, Claudia M. Parra-Giraldo
Summary: This study identified the mechanism of caspofungin resistance, evaluated the proteomic response to caspofungin, and found that calmodulin inhibition can restore caspofungin susceptibility, reduce stress response, biofilm formation, and pathogenicity in vivo.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Microbiology
Norida Velez, Lucia Monteoliva, Zilpa-Adriana Sanchez-Quitian, Ahinara Amador-Garcia, Rocio Garcia-Rodas, Andres Ceballos-Garzon, Concha Gil, Patricia Escandon, Oscar Zaragoza, Claudia-Marcela Parra-Giraldo
Summary: This study found that the combination of iron and copper can enhance the pathogenicity of Cryptococcus neoformans and increase the abundance of proteins related to virulence factors. This suggests that the uptake of metals may affect the pathogenicity of fungi.
Article
Microbiology
Raquel Martinez-Lopez, Maria Luisa Hernaez, Esther Redondo, Guillermo Calvo, Sonja Radau, Mercedes Pardo, Concha Gil, Lucia Monteoliva
Summary: This first analysis of HEVs of C. albicans has revealed distinct differences between them and the YEVs of C. albicans, indicating their importance and potential use in identifying new diagnostic markers and treatment targets for C. albicans infections. The data suggest different mechanisms of YEVs and HEVs biogenesis, as well as different roles in cell biology and host interaction. YEVs play a significant role in cell wall maintenance, while HEVs are more closely associated with virulence, exerting greater effects on human immune cells. Notably, an active 20S proteasome complex is exclusively secreted by HEVs. Further investigation into the functions of proteins exclusively found in HEVs could open up new research avenues in combating C. albicans.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Claudia Saralegui, Carmen Garcia-Duran, Eduardo Romeu, Maria Luisa Hernaez-Sanchez, Ainhize Maruri, Natalia Baston-Paz, Adelaida Lamas, Saioa Vicente, Estela Perez-Ruiz, Isabel Delgado, Carmen Luna-Paredes, Juan de Dios Caballero, Javier Zamora, Lucia Monteoliva, Concepcion Gil, Rosa del Campo
Summary: In recent years, various techniques have been used to study microbial ecosystems, with 16S rRNA gene sequencing being the most common method. Metaproteomics can identify the interaction between microorganisms and human cells, but the available databases are limited and imprecise. This study compares the differences between 16S rRNA amplicon sequencing and metaproteomics in identifying microorganisms and analyzing alpha diversity. Additionally, the study explores the establishment of intestinal ecosystems in newborns with cystic fibrosis, characterized by host inflammation and enrichment of Ruminococcus gnavus.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Sara Hernando-Amado, Carla Lopez-Causape, Pablo Laborda, Fernando Sanz-Garcia, Antonio Oliver, Jose Luis Martinez
Summary: Collateral sensitivity (CS) is an evolutionary trade-off where resistance to one antibiotic leads to increased susceptibility to another. This study analyzed the robustness of CS in clinical strains of Pseudomonas aeruginosa, identifying a robust CS pattern associated with short-term evolution in the presence of ciprofloxacin. The findings suggest that identification of robust CS patterns can form the basis for developing evolutionary strategies to tackle bacterial infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Roberta Genova, Pablo Laborda, Trinidad Cuesta, Jose Luis Martinez, Fernando Sanz-Garcia
Summary: Understanding the consequences of drug resistance in bacterial physiology is crucial for exploiting its weaknesses. Collateral sensitivity, a potentially exploitable phenotype, may not be conserved among different isolates. Identifying robust and conserved collateral sensitivity patterns is important for translating this knowledge into clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Microbiology
Fernando Sanz-Garcia, Teresa Gil-Gil, Pablo Laborda, Paula Blanco, Luz-Edith Ochoa-Sanchez, Fernando Baquero, Jose Luis Martinez, Sara Hernando-Amado
Summary: In this Review, the authors discuss how eco-evolutionary-based approaches can contribute to the development of successful antibiotic therapies. They explore the exploitation of evolutionary trade-offs, targeting bacterial metabolism, and studying the ancestral functions of antibiotic resistance determinants. These approaches are crucial for tackling the urgent problem of antibiotic resistance and preserving the efficacy of current antibiotics.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sara Hernando-Amado, Pablo Laborda, Jose Luis Martinez
Summary: In this study, the authors induced ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa and found transient collateral sensitivity to tobramycin. This non-inherited induction of antibiotic resistance allows for the eradication of antibiotic-resistant strains when combined with tobramycin. These results suggest that transient collateral sensitivity could be a new evolutionary strategy to combat antibiotic-resistant infections.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Ada Munoz-Cazalla, Jose L. Martinez, Pablo Laborda
Summary: Efflux pumps are important determinants of antibiotic resistance in Pseudomonas aeruginosa, and they are also involved in other bacterial activities such as quorum sensing-mediated regulation of virulence. However, the interconnection between efflux pumps and bacterial metabolism remains unclear. This study found that phenylethylamine acts as both an inducer and substrate of the MexCD-OprJ efflux pump, which is involved in antibiotic resistance and extrusion of quorum-sensing signal precursors in P. aeruginosa. While phenylethylamine did not increase antibiotic resistance, it reduced the virulence potential by suppressing the production of toxins and inhibiting swarming motility through the downregulation of quorum sensing signaling molecules.
MICROBIAL BIOTECHNOLOGY
(2023)
Editorial Material
Microbiology
Sara Hernando-Amado, Jose Luis Martinez
Review
Biology
Fernando Baquero, Jose-Luis Martinez, Alvaro Sanchez, Miguel D. Fernandez-de-Bobadilla, Alvaro San-Millan, Jeronimo Rodriguez-Beltran
Summary: This study proposes the concept of structural epistasis to highlight the role of physical interactions between molecules located in specific spaces inside the bacterial cell in the emergence of novel phenotypes.
Article
Biochemistry & Molecular Biology
Teresa Gil-Gil, Trinidad Cuesta, Sara Hernando-Amado, Jose Antonio Reales-Calderon, Fernando Corona, Juan F. Linares, Jose L. Martinez
Summary: Pseudomonas aeruginosa is a widespread nosocomial opportunistic pathogen with many virulence determinants. The lack of Crc in Pseudomonas aeruginosa leads to a defective Type III Secretion System (T3SS) activity, which is caused by reduced expression of T3SS genes and impaired protein secretion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biotechnology & Applied Microbiology
Jose L. Martinez, Fernando Baquero
Summary: Antibiotic resistance is a major concern for human health, and further research is needed to understand the mechanisms of resistance and its impact on bacterial physiology. Novel strategies are necessary to address this problem, beyond the development of new antibiotics or restrictions on their use, in order to effectively treat infections.
MICROBIAL BIOTECHNOLOGY
(2023)
Article
Microbiology
Teresa Gil-Gil, Jose Ramon Valverde, Jose Luis Martinez, Fernando Corona
Summary: Pseudomonas aeruginosa utilizes carbon sources in a hierarchical way, and its carbon catabolic repression is regulated by Hfq and Crc at the post-transcriptional level. The small RNA CrcZ plays a role in sequestering the Crc-Hfq complex to enable translation of target mRNAs under no catabolic repression conditions. Crc and Hfq not only regulate carbon source utilization but also impact P. aeruginosa virulence and antibiotic resistance.
MICROBIOLOGY SPECTRUM
(2023)
