Review
Immunology
Wanhai Qin, Brendon P. Scicluna, Tom van der Poll
Summary: DNA methylation plays a key role in the immune response to bacteria by regulating gene expression. Despite being traditionally considered a stable modification, accumulating evidence suggests that DNA methylation patterns can change rapidly in response to different environments and pathogens. Proteins regulating DNA methylation, such as DNA methyltransferases and ten-eleven translocation methylcytosine dioxygenases, may also be modulated by bacteria during infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Alice H. Costain, Alexander T. Phythian-Adams, Stefano A. P. Colombo, Angela K. Marley, Christian Owusu, Peter C. Cook, Sheila L. Brown, Lauren M. Webb, Rachel J. Lundie, Hermelijn H. Smits, Matthew Berriman, Andrew S. MacDonald
Summary: Schistosomiasis is a globally significant disease, and the severity and pathology of the infection are directly related to the host's immune response. However, the current understanding of the immune trajectory of schistosomiasis during infection and across different tissue sites is not comprehensive and up-to-date. This study investigates the immune responses at different stages of the parasite lifecycle and in three affected tissue sites, and provides novel insights into the transcriptomic changes in the liver during schistosomiasis. The study also highlights the crucial role of CD11c(+) cells in coordinating and regulating Th2 inflammation during infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Ya-Lang Huang, Ming-Ting Huang, Pei-Shan Sung, Teh-Ying Chou, Ruey-Bing Yang, An-Suei Yang, Chung-Ming Yu, Yu-Wen Hsu, Wei-Chiao Chang, Shie-Liang Hsieh
Summary: Ya-Lang Huang et al. report a mechanism for TLR3-mediated signaling after immune simulation and influenza virus infection by way of the co-receptor CLEC18A. This study found that a single amino acid change in CLEC18A(S339R) can enhance the production of type I and type III interferons to suppress viral replication, and increase mice survival rate after flu infection infection.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Chang Hyun Song, Young Ho Kim, Manisha Naskar, Byron W. Hayes, Mathew A. Abraham, Joo Hwan Noh, Gyeongseo Suk, Min Jung Kim, Kyu Sang Cho, Minhye Shin, Eun-Jin Lee, Soman N. Abraham, Hae Woong Choi
Summary: This study found that compared to healthy women, female patients with recurrent urinary tract infections (UTIs) have significantly reduced population of Lactobacilli in the bladder. Exposing infected human bladder epithelial cells to L. crispatus in vitro greatly reduced the intracellular load of uropathogenic Escherichia coli (UPEC). The adherence of Lactobacilli to bladder epithelial cells increased the production of type I interferon (IFN), which enhanced the expression of cathepsin D within lysosomes containing UPECs, leading to their elimination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Fisheries
Lingfeng Guan, Xiaozhi Wen, Zihan Zhang, Liqun Wang, Xinyue Zhang, Min Yang, Shaowen Wang, Qiwei Qin
Summary: In this study, a novel Rab1 homolog (EcRab1) from Epinephelus coioides was cloned, and its roles during virus infection and host immune responses were investigated. The results showed that EcRab1 inhibited RGNNV infection and positively regulated interferon (IFN) immune and inflammatory responses.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Review
Microbiology
Qinglin Zhang, Qizhen Jia, Wenying Gao, Wenyan Zhang
Summary: This article summarizes the function of DUBs in modulating viral infection and highlights their importance as therapeutic targets for antiviral treatment.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Fisheries
Junrong Li, Liqun Wang, Xinyue Zhang, Xiaozhi Wen, Xinyan Wei, Qiwei Qin, Shaowen Wang
Summary: This study identified and characterized AnxA2 (EcAnxA2) in Epinephelus coioides and investigated its role in RGNNV infection. EcAnxA2 was widely expressed in different tissues and its expression was significantly increased after RGNNV infection. Overexpression of EcAnxA2 enhanced RGNNV infection, while knockdown of EcAnxA2 reduced infection. EcAnxA2 also modulated the host immune response by regulating the transcription of interferon-related and inflammatory factors. These findings provide new insights into the role of AnxA2 in fish during virus infection.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Fisheries
Mengru Jin, Jiaojiao He, Jun Li, Yonghua Hu, Dongmei Sun, Hanjie Gu
Summary: The study reveals that YccA is a novel virulence factor of E. piscicida and essential for bacterial pathogenicity through evasion of the host's innate immune functions.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Review
Cell Biology
Gerardo Manuel Corral-Ruiz, Luvia Enid Sanchez-Torres
Summary: The complex relationship between helminths, microbiota, and humans plays a crucial role in human evolution and immune system development. Understanding this relationship is vital for maintaining health and finding new therapeutic approaches.
CELLULAR IMMUNOLOGY
(2022)
Article
Immunology
Tanvir Bamra, Taj Shafi, Sushmita Das, Manjay Kumar, Manas Ranjan Dikhit, Ajay Kumar, Ashish Kumar, Kumar Abhishek, Krishna Pandey, Abhik Sen, Pradeep Das
Summary: Leishmania parasite secretes numerous proteins during in vitro cultivation, with Mevalonate kinase playing a significant role in infection. Visceral Leishmaniasis is a persistent infection caused by Leishmania donovani, partly due to immune evasion. The novel secretory protein MVK aids in parasite internalization and modulation of the host immune response through signal transduction pathways.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rafael de Freitas e Silva, Gabriela Bassi, Niels Olsen Saraiva Camara, Nilmar Silvio Moretti
Summary: Global warming is altering the global distribution of pathogens, making humans more vulnerable to new infections. The human response to microbes involves complex immune mechanisms, including regulation of gene expression and metabolism of immune cells. Protein lysine acetylation plays a crucial role in immunity, with lysine acetyltransferases promoting acetylation and lysine deacetylases reducing it. These enzymes, known as HDACs and Sirtuins, are present in various cellular compartments and impact cellular pathways such as metabolism, gene expression, and cell proliferation. Understanding the role of Sirtuins in host responses to infections can provide insights into pathogen manipulation and potential therapeutic targets for preventing infections.
MOLECULAR IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wenjie Yang, Yang Li, Diana Boraschi
Summary: Plastic pollution is a global problem that poses risks to the environment and human health. Discarded plastic degrades into microplastics (MPs) in the environment, which can interact with microorganisms and biomolecules. These interactions can modify the characteristics of microbes and biomolecules, potentially affecting the immune response and leading to risks to human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Weitao Shen, Yu Chen, Ning Wang, Ping Wan, Zhenyan Peng, Huajin Zhao, Wei Wang, Lilin Xiong, Shenghu Zhang, Ran Liu
Summary: This study analyzed the removal capacity of antibiotics, antibiotic resistance determinants, and bacteria in sewage treatment plants and their impact on environmental waters. The results showed that the removal capacity of bacteria was poor in summer, and the concentration of fluoroquinolone was higher in the effluent. Furthermore, the study found that the relationship between these pollutants differed between summer and winter.
JOURNAL OF ENVIRONMENTAL MANAGEMENT
(2022)
Article
Biochemistry & Molecular Biology
Boaz Kalmovich, Daniella Rahamim-Cohen, Shirley Shapiro Ben David
Summary: Antibiotic overuse and underuse are common issues in urgent care settings due to diagnostic uncertainty. Previous clinical validation of a host-based test called MeMed BV, which distinguishes bacterial and viral infections, has prompted an examination of its impact on antibiotic prescription in a real-world setting. Results showed that physicians were more likely to prescribe antibiotics in accordance with the BV result, leading to a reduction in antibiotic prescriptions for patients with viral BV results and better antibiotic use overall.
Article
Oncology
Laura M. Chambers, Chad M. Michener, Peter G. Rose, Ofer Reizes, Meng Yao, Roberto Vargas
Summary: This retrospective cohort study aimed to investigate the impact of antibiotics (ABX) on immunotherapy (ICI) response rate (RR), progression-free survival (PFS), and overall survival (OS) in women with recurrent endometrial (EC), cervical (CC) and ovarian cancer (OC). The results showed that the use of antibiotics had different effects on ICI RR, PFS, and OS in these women, with some ABX significantly reducing RR, PFS, and OS.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Biology
George H. Youlden, Vito Ricci, Xuan Wang-Kan, Laura J. V. Piddock, Sara Jabbari, John R. King
Summary: Efflux pumps are mechanisms of resistance in bacteria that can expel antibiotics to confer resistance. Overexpression of efflux pumps can lead to multi-drug resistance. By studying the gene regulation network associated with efflux, a mathematical model is presented and analyzed using time-dependent asymptotic analysis.
JOURNAL OF MATHEMATICAL BIOLOGY
(2021)
Article
Microbiology
Christopher A. Darlow, Fernando Docobo-Perez, Nicola Farrington, Adam Johnson, Laura McEntee, Jennifer Unsworth, Ana Jimenez-Valverde, Silke Gastine, Ruwanthi Kolamunnage-Dona, Renata M. A. de Costa, Sally Ellis, Francois Franceschi, Joseph F. Standing, Mike Sharland, Michael Neely, Laura Piddock, Shampa Das, William Hope
Summary: Antimicrobial resistance in neonatal sepsis is a global issue, with high mortality rates in low- and middle-income countries. A combination therapy of fosfomycin and amikacin shows enhanced bactericidal activity and synergy against resistant strains. Monte Carlo simulations support the efficacy of this combination regimen for the treatment of neonatal sepsis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Elena Carrara, Alessia Savoldi, Laura J. Piddock, Francois Franceschi, Sally Ellis, Mike Sharland, Adrian John Brink, Patrick N. A. Harris, Gabriel Levy-Hara, Anusha Rohit, Constantinos Tsioutis, Hiba Zayyad, Christian Giske, Margherita Chiamenti, Damiano Bragantini, Elda Righi, Anna Gorska, Evelina Tacconelli
Summary: The optimal treatment for carbapenem-resistant Gram-negative bacteria infections varies globally, with dual combination therapy being the preferred treatment scheme. However, there is disagreement among clinicians regarding the definition of 'combination therapy.'
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Review
Infectious Diseases
Luigia Scudeller, Elda Righi, Margherita Chiamenti, Damiano Bragantini, Giulia Menchinelli, Paolo Cattaneo, Christian G. Giske, Thomas Lodise, Maurizio Sanguinetti, Laura J. Piddock, Francois Franceschi, Sally Ellis, Elena Carrara, Alessia Savoldi, Evelina Tacconelli
Summary: The efficacy of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro studies suggest that combinations of polymyxins and carbapenems show high or moderate synergism against CR-GNB. Well-designed in vitro studies are crucial for guiding the selection of combination therapies in clinical trials and improving the armamentarium against carbapenem-resistant bacteria.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Immunology
Laura J. Piddock, Jean-Pierre Paccaud, Seamus O'Brien, Michelle Childs, Rohit Malpani, Manica Balasegaram
Summary: Antibiotics are crucial for modern medicine, but commercial developers do not see sufficient profitability to address public need. Nonprofit research and development organizations have the potential to collaborate and provide new antibiotics.
CLINICAL INFECTIOUS DISEASES
(2022)
Editorial Material
Infectious Diseases
Laura J. Piddock
Summary: The discovery of antibiotics revolutionized medicine, but now antimicrobial resistance is becoming a greater problem than the development of new antimicrobials. New political and economic models are needed to address this escalating crisis. This article examines the challenges and proposes strategies to overcome them.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Maria Laura Ciusa, Robert L. Marshall, Vito Ricci, Jack W. Stone, Laura J. Piddock
Summary: The study found that inhibiting the AcrB efflux pump in Escherichia coli did not significantly increase the expression of other efflux pump genes, indicating that there is no compensatory mechanism to overcome efflux inhibition.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Christopher A. Darlow, Nicola Farrington, Adam Johnson, Laura McEntee, Jennifer Unsworth, Ana Jimenez-Valverde, Ruwanthi Kolamunnage-Dona, Renata M. A. Da Costa, Sally Ellis, Francois Franceschi, Mike Sharland, Michael Neely, Laura J. Piddock, Shampa Das, William Hope
Summary: This study assessed the efficacy of flomoxef and fosfomycin as a potential alternative treatment for neonatal sepsis in low- and middle-income countries. The combination therapy showed synergy in terms of bacterial killing and prevention of fosfomycin resistance. The findings suggest that flomoxef/fosfomycin could be an effective regimen for neonatal sepsis in settings with antimicrobial resistance.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Editorial Material
Public, Environmental & Occupational Health
Isaac Weldon, Susan Rogers Van Katwyk, Gian Luca Burci, Thana C. de Campos, Mark Eccleston-Turner, Helen R. Fryer, Alberto Giubilini, Thomas Hale, Mark Harrison, Stephanie Johnson, Claas Kirchhelle, Kelley Lee, Kathleen Liddell, Marc Mendelson, Gorik Ooms, James Orbinski, Laura Iv Piddock, John-Arne Rottingen, Julian Savulescu, Andrew C. Singer, A. M. Viens, Clare Wenham, Mary E. Wiktorowicz, Shehla Zaidi, Steven J. Hoffman
AMERICAN JOURNAL OF PUBLIC HEALTH
(2022)
Article
Infectious Diseases
Jessica M. A. Blair, Pauline Siasat, Helen E. McNeil, Abigail Colclough, Vito Ricci, Amelia J. Lawler, Hind Abdalaal, Michelle M. C. Buckner, Alison Baylay, Stephen J. Busby, Laura J. Piddock
Summary: In this study, it was found that EnvR is a potent repressor of acrAB transcription in Salmonella, and can override binding by RamA, thus preventing multidrug resistance to clinically useful drugs. Finding novel tools to increase EnvR expression may form the basis of a new way to prevent or treat multidrug-resistant infections.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Christopher A. Darlow, Laura McEntee, Adam Johnson, Nicola Farrington, Jennifer Unsworth, Ana Jimenez-Valverde, Bhavana Jagota, Ruwanthi Kolamunnage-Dona, Renata M. A. Da Costa, Sally Ellis, Francois Franceschi, Mike Sharland, Michael Neely, Laura Piddock, Shampa Das, William Hope
Summary: The combination of flomoxef and amikacin shows synergistic effects in bacterial killing and prevention of amikacin resistance. It effectively kills a majority of Enterobacterales isolates with a range of flomoxef/amikacin MICs, making it a potentially clinically effective regimen for the empirical treatment of neonatal sepsis in LMIC settings. Further assessment in a clinical trial is recommended.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Editorial Material
Infectious Diseases
Laura Piddock
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2023)
Article
Microbiology
Alistair D. Middlemiss, James R. J. Haycocks, Anne M. Stringer, Laura J. V. Piddock, Joseph T. Wade, David C. Grainger
Summary: The transcription factors MarA, SoxS, Rob and RamA control overlapping stress responses in enteric bacteria and their constitutive expression is linked to antibiotic resistance. The study mapped the binding sites of these factors across the Salmonella Typhimurium genome and identified changes in transcription start sites. This information helps disentangle direct and indirect gene regulation effects and deduce promoter architecture within the regulon. The control of csgD, which is involved in biofilm formation, is particularly sensitive to SoxS repression in Salmonella Typhimurium unlike in Escherichia coli where MarA indirectly regulates csgD expression.
Article
Infectious Diseases
Alasdair P. Macgowan, M. L. G. Attwood, Alan R. Noel, R. Barber, Zachary Aron, Timothy J. Opperman, Elizabeth Grimsey, Jack Stone, Vito Ricci, L. J. Piddock
Summary: This study investigated the pharmacodynamic characteristics of efflux pump inhibitors (EPIs) in Escherichia coli through in vitro experiments and gene sequencing. The results showed that the AUC of chlorpromazine and PA beta N was most closely related to the reduction in bacterial load, while the T > threshold of MBX-4191 was the driver for bacterial load reduction. No changes in population profiles were observed with the combination of ciprofloxacin + EPIs, but mutations were detected in gyrA, gyrB, and marR.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Biotechnology & Applied Microbiology
Ursula Theuretzbacher, Benjamin Blasco, Maelle Duffey, Laura J. V. Piddock
Summary: Advances in genomics, systems biology, protein structure determination, and artificial intelligence provide new opportunities for target-based antibacterial drug discovery. Multiple criteria, including target essentiality, conservation, homology with human genes, and drug-like binding potential, need to be considered in selecting a suitable target. Subcellular location and the risk of drug resistance also play important roles in the process. This review highlights promising targets and inhibitors for Gram-negative bacteria and lessons learned from past drug discovery programs.
NATURE REVIEWS DRUG DISCOVERY
(2023)
