Article
Biochemistry & Molecular Biology
Vidhu Agarwal, Tara Chand Yadav, Akhilesh Tiwari, Pritish Varadwaj
Summary: Antimicrobial resistance is a growing global health challenge. Bacterial infections have developed resistance against beta-lactam antibiotics through various mechanisms, including the production of novel beta-lactamase enzymes. These bacteria have also developed resistance against beta-lactamase inhibitors. Investigating the role of important residues in altering and expanding the spectrum activity of these enzymes is necessary to understand beta-lactamase-mediated resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Matthijs J. van Haren, Kamaleddin H. M. E. Tehrani, Ioli Kotsogianni, Nicola Wade, Nora C. Bruchle, Vida Mashayekhi, Nathaniel I. Martin
Summary: The increasing prevalence of metallo-beta-lactamase (MBL)-expressing bacteria is a worrying trend in antibiotic resistance. Studies have shown that zinc ions, which are essential for the hydrolytic activity of MBLs, can be targeted for inhibition. Researchers have developed a series of cephalosporin prodrugs that exhibit potent activity against MBLs and can act synergistically with specific antibiotics.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Microbiology
T. A. Alsenani, S. L. Viviani, V Kumar, M. A. Taracila, C. R. Bethel, M. D. Barnes, K. M. Papp-Wallace, R. K. Shields, M. H. Nguyen, C. J. Clancy, R. A. Bonomo, F. van den Akker
Summary: The structural study of KPC-2 D179 variants revealed destabilization of the Omega loop, contributing to ceftazidime-avibactam resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Liqiang Hu, Huixin Yang, Tao Yu, Fangfang Chen, Runqiu Liu, Shuyuan Xue, Shuangzhan Zhang, Wuyu Mao, Changge Ji, Hao Wang, Hexin Xie
Summary: This study demonstrates the effectiveness of stereochemically altered cephalosporins as potent inhibitors against NDM-1, a major cause of antibiotic resistance. The findings provide a new approach to combat antibiotic resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Tek Narsingh Malla, Kara Zielinski, Luis Aldama, Sasa Bajt, Denisse Feliz, Brendon Hayes, Mark Hunter, Christopher Kupitz, Stella Lisova, Juraj Knoska, Jose Manuel Martin-Garcia, Valerio Mariani, Suraj Pandey, Ishwor Poudyal, Raymond G. Sierra, Alexandra Tolstikova, Oleksandr Yefanov, Chung Hong Yoon, Abbas Ourmazd, Petra Fromme, Peter Schwander, Anton Barty, Henry N. Chapman, Emina A. Stojkovic, Alexander Batyuk, Sebastien Boutet, George N. Phillips, Lois Pollack, Marius Schmidt
Summary: This study used mix-and-inject serial crystallography to trace atomic positions and elucidate essential enzymatic functions at the atomic level. The results reveal detailed information about ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection from the same set of data, providing insights into the inhibition of Mycobacterium tuberculosis enzyme by sulbactam.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Severine Rangama, Ian D. E. A. Lidbury, Jennifer M. Holden, Chiara Borsetto, Andrew R. J. Murphy, Peter M. Hawkey, Elizabeth M. H. Wellington
Summary: In this study, strains of E. coli isolated downstream of a wastewater treatment plant in a river were found to carry multiple resistance genes, including bla(CTX-M-15) encoding an ESBL. E. coli strain 48 was shown to protect susceptible E. coli strain 33 from cefotaxime through secretion of a stable ESBL for at least 24 hours. CTX-M-15 was identified as the major secreted ESBL responsible for this protective effect, suggesting a public goods service for the survival of susceptible bacteria in the presence of cefotaxime.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Chemistry, Medicinal
Rong Li, Xi Chen, Cong Zhou, Qing-Qing Dai, Lingling Yang
Summary: The effectiveness of beta-lactam antibiotics is increasingly influenced by serine beta-lactamases (SBLs) and metallo beta-lactamases (MBLs). Developing effective beta-lactamase inhibitors is important to extend the use of beta-lactam antibiotics. Although SBL inhibitors have been approved for clinical use, there are currently no MBL inhibitors or MBL/SBL dual-action inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Yang Ding, Zheng Li, Chenchen Xu, Wenjing Qin, Qiong Wu, Xuchun Wang, Xiamin Cheng, Lin Li, Wei Huang
Summary: Beta-lactam antibiotics are important inventions in treating infections, but the emergence of beta-lactamase in bacteria leads to drug resistance. Various detection methods and inhibitors are available, and designing improved probes may help overcome bacterial resistance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Microbiology
T. A. Alsenani, S. L. Viviani, K. M. Papp-Wallace, R. A. Bonomo, F. van den Akker
Summary: KPC-2 is a bacterial strain that is resistant to carbapenem drugs and recent variants have developed resistance to other drugs as well. This study focuses on the structural changes in KPC-2 D179N when bound to avibactam and relebactam, providing insight into the decreased affinity of D179Y variant to avibactam and potential design of novel beta-lactamase inhibitors.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Peixin Fan, Zhengxin Ma, Arianna J. Partow, Miju Kim, Grace M. Shoemaker, Ruwen Tan, Zhaohui Tong, Corwin D. Nelson, Yeongseon Jang, Kwangcheol C. Jeong
Summary: Antimicrobial resistance poses a major global threat, especially multidrug resistant ESBL-producing pathogens. Researchers developed a novel therapy combining cephalosporin antibiotics and beta-lactamase inhibitors encapsulated in chitosan nanoparticles, effectively combating drug-resistant Enterobacteriaceae and showing promising potential for treating critically important infections.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Microbiology
Lekshmi Narendrakumar, Medha Chakraborty, Shashi Kumari, Deepjyoti Paul, Bhabatosh Das
Summary: Beta-lactam antibiotics are widely used antimicrobial agents, but their misuse has led to the emergence of resistance in clinically important bacterial pathogens. This review summarizes the success stories of beta-lactamase inhibitors and prospective beta-lactam potentiators, and discusses the challenges in translating these potentiation strategies from bench to bedside. Other mechanisms to reduce global antimicrobial resistance burden are also explored.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Catherine L. Tooke, Philip Hinchliffe, Michael Beer, Kirill Zinovjev, Charlotte K. Colenso, Christopher J. Schofield, Adrian J. Mulholland, James Spencer
Summary: KPC-2 is a carbapenemase that confers resistance to β-lactam antibiotics in Gram-negative pathogens. The flexible a-loop in KPC-2 plays a role in catalytic activity, while carbapenemase activity is mainly due to efficient deacylation of the A2-enamine acyl-enzyme tautomer. Quantum mechanics/molecular mechanics simulations reveal the specific reactivity of the two isomers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Nicola Wade, Kamaleddin H. M. E. Tehrani, Nora C. Bruchle, Matthijs J. van Haren, Vida Mashayekhi, Nathaniel I. Martin
Summary: This study elucidated the inhibitory mechanisms of a panel of structurally distinct MBL inhibitors, finding clear differences in terms of IC50 value, metal binding ability, and synergy with meropenem. The capacity of an inhibitor to strongly chelate zinc does not explicitly determine potent MBL inhibition and synergy with meropenem.
Article
Pharmacology & Pharmacy
Yuejuan Zhang, Cheng Chen, Bin Cheng, Lei Gao, Chuan Qin, Lixia Zhang, Xu Zhang, Jun Wang, Yi Wan
Summary: Carbapenem resistance caused by OXA-48 beta-lactamase is a global health threat. In this study, quercetin and its analogs were identified as potent inhibitors of OXA-48, with the ability to restore the antibacterial efficacy of certain antibiotics against OXA-48-producing bacteria. Mechanism studies revealed that these compounds interacted with OXA-48 through hydrogen bonding, leading to the inhibition of its activity. Additionally, quercetin showed antimicrobial activity in combination with certain antibiotics in a mouse infection model.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Jagir R. Hussan, Stuart G. Irwin, Brya Mathews, Simon Swift, Dustin L. Williams, Jillian Cornish
Summary: This study investigates the role of lactoferrin as an adjuvant in enhancing the efficacy of broad-spectrum antibiotics. The findings suggest that lactoferrin at optimal doses can enhance the effects of β-lactam antibiotics against Staphylococcus aureus, while sub-inhibitory doses of lactoferrin reduce the efficacy of the antibiotics.
Editorial Material
Immunology
Robert L. Atmar, Sasirekha Ramani
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Virology
Wanzhi Huang, Victoria Soeung, David M. Boragine, Liya Hu, B. V. Venkataram Prasad, Mary K. Estes, Robert L. Atmar, Timothy Palzkill
Summary: This study utilized a high-resolution method to map multiple antibody binding sites simultaneously from complex serum samples. The results indicated that a relatively small number of sites on the virus bind a large number of independently generated antibodies, suggesting that immunodominance plays a role in the humoral immune response to NoV infections.
JOURNAL OF VIROLOGY
(2021)
Article
Microbiology
Khalil Ettayebi, Victoria R. Tenge, Nicolas W. Cortes-Penfield, Sue E. Crawford, Frederick H. Neill, Xi-Lei Zeng, Xiaomin Yu, Vijayalakshmi Ayyar, Douglas Burrin, Sasirekha Ramani, Robert L. Atmar, Mary K. Estes
Summary: The study demonstrates that optimization of cultivation conditions in human intestinal enteroid cultures can effectively replicate multiple strains of human noroviruses (HuNoVs), which is crucial for research on HuNoV biology and the development of treatment methods.
Letter
Medicine, General & Internal
Elizabeth F. Eisenmenger, Emmanuel Guajardo, Natalie Finch, Robert L. Atmar, Zaven Sargsyan
AMERICAN JOURNAL OF MEDICINE
(2021)
Article
Immunology
Hana M. El Sahly, Robert L. Atmar, Eli Sendra, Ashley Wegel, Wendy A. Keitel
Summary: The study concluded that the combination of topical imiquimod with ID MIV A/H5N1 was safe but did not result in improved serologic responses to the vaccine.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Immunology
Elizabeth Wenqian Wang, Jacqueline G. Parchem, Robert L. Atmar, Eva H. Clark
Summary: Despite the lack of data on vaccine safety in pregnant and breastfeeding individuals, the known risks of COVID-19 during pregnancy likely outweigh the potential risks of SARS-CoV-2 vaccines, which have demonstrated reassuring safety and efficacy profiles in nonpregnant populations.
OPEN FORUM INFECTIOUS DISEASES
(2021)
Review
Virology
Victoria R. Tenge, Kosuke Murakami, Wilhelm Salmen, Shih-Ching Lin, Sue E. Crawford, Frederick H. Neill, B. V. Venkataram Prasad, Robert L. Atmar, Mary K. Estes
Summary: Laboratory cultivation of viruses is essential for studying viral replication, detection methods, drug development, and antiviral research. Some viruses, such as human noroviruses and hepatitis B and C viruses, have difficulties replicating in cell lines, with tropism for the intestine and liver. Understanding the role of bile acids and receptors in virus replication is crucial for developing and optimizing culture systems for these viruses.
Article
Primary Health Care
Larissa Grigoryan, Roger Zoorob, George Germanos, Mohamad Sidani, Matthew Horsfield, Fareed Khan, Mohammad Zare, Melanie Goebel, Robert Atmar, Barbara Trautner
Summary: The multifaceted stewardship intervention significantly increased guideline adherence for antibiotic choice and duration in the treatment of uncomplicated cystitis, compared to the control group. Future research is needed to further explore the scalability and sustainability of similar interventions in primary care settings.
FAMILY MEDICINE AND COMMUNITY HEALTH
(2021)
Article
Medicine, General & Internal
R. L. Atmar, K. E. Lyke, M. E. Deming, L. A. Jackson, A. R. Branche, H. M. El Sahly, C. A. Rostad, J. M. Martin, C. Johnston, R. E. Rupp, M. J. Mulligan, R. C. Brady, R. W. Frenck, M. Backer, A. C. Kottkamp, T. M. Babu, K. Rajakumar, S. Edupuganti, D. Dobrzynski, R. N. Coler, C. M. Posavad, J. Archer, S. Crandon, S. U. Nayak, D. Szydlo, J. A. Zemanek, C. P. Dominguez Islas, E. R. Brown, M. S. Suthar, M. J. McElrath, A. B. McDermott, D. C. Montefiori, A. Eaton, K. M. Neuzil, D. S. Stephens, P. C. Roberts, J. H. Beigel
Summary: This study investigated the efficacy of homologous and heterologous booster vaccines in adults who had completed a primary Covid-19 vaccine regimen. The results showed that both types of booster vaccines were safe and immunogenic.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Letter
Medicine, General & Internal
Rolando Pajon, Nicole A. Doria-Rose, Xiaoying Shen, Stephen D. Schmidt, Sijy O'Dell, Charlene McDanal, Wenhong Feng, Jin Tong, Amanda Eaton, Maha Maglinao, Haili Tang, Kelly E. Manning, Venkata-Viswanadh Edara, Lilin Lai, Madison Ellis, Kathryn M. Moore, Katharine Floyd, Stephanie L. Foster, Christine M. Posavad, Robert L. Atmar, Kirsten E. Lyke, Tongqing Zhou, Lingshu Wang, Yi Zhang, Martin R. Gaudinski, Walker P. Black, Ingelise Gordon, Mercy Guech, Julie E. Ledgerwood, John N. Misasi, Alicia Widge, Nancy J. Sullivan, Paul C. Roberts, John H. Beigel, Bette Korber, Lindsey R. Baden, Hana El Sahly, Spyros Chalkias, Honghong Zhou, Jing Feng, Bethany Girard, Rituparna Das, Anne Aunins, Darin K. Edwards, Mehul S. Suthar, John R. Mascola, David C. Montefiori
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Virology
Victoria R. Tenge, Liya Hu, B. V. Venkataram Prasad, Goran Larson, Robert L. Atmar, Mary K. Estes, Sasirekha Ramani
Summary: Recognition of cell-surface glycans is crucial for virus attachment to host cells. Studies on HuNoVs show that HBGA glycan structures are important for infection, and the antibody-mediated neutralization mechanism has been explored. The use of novel culture systems has confirmed the necessity of fucosylated HBGAs for HuNoV infection.
Review
Virology
Boyang Zhao, Liya Hu, Yongcheng Song, Ketki Patil, Sasirekha Ramani, Robert L. Atmar, Mary K. Estes, B. V. Venkataram Prasad
Summary: Human norovirus (HuNoV) infection is a global health and economic burden with no licensed vaccines or antiviral drugs available. Developing HuNoV protease inhibitors by targeting the enzyme's active site faces challenges due to subtle differential conformational flexibility and structural differences in the active site and substrate-binding pockets. Further comparative analysis of available HuNoV protease structures is needed to identify novel strategies for effective inhibitor design and development.
Article
Critical Care Medicine
Andre C. Kalil, Aneesh K. Mehta, Thomas F. Patterson, Nathaniel Erdmann, Carlos A. Gomez, Mamta K. Jain, Cameron R. Wolfe, Guillermo M. Ruiz-Palacios, Susan Kline, Justino Regalado Pineda, Anne F. Luetkemeyer, Michelle S. Harkins, Patrick E. H. Jackson, Nicole M. Iovine, Victor F. Tapson, Myoung-don Oh, Jennifer A. Whitaker, Richard A. Mularski, Catharine Paules, Dilek Ince, Jin Takasaki, Daniel A. Sweeney, Uriel Sandkovsky, David L. Wyles, Elizabeth Hohmann, Kevin A. Grimes, Robert Grossberg, Maryrose Laguio-Vila, Allison A. Lambert, Diego Lopez de Castilla, EuSuk Kim, LuAnn Larson, Claire R. Wan, Jessica J. Traenkner, Philip O. Ponce, Jan E. Patterson, Paul A. Goepfert, Theresa A. Sofarelli, Satish Mocherla, Emily R. Ko, Alfredo Ponce de Leon, Sarah B. Doernberg, Robert L. Atmar, Ryan C. Maves, Fernando Dangond, Jennifer Ferreira, Michelle Green, Mat Makowski, Tyler Bonnett, Tatiana Beresnev, Varduhi Ghazaryan, Walla Dempsey, Seema U. Nayak, Lori Dodd, Kay M. Tomashek, John H. Beigel
Summary: This study compared the efficacy of interferon beta-1a in combination with remdesivir versus remdesivir alone in hospitalised COVID-19 patients. The results showed no significant difference in time to recovery and mortality rate between the interferon beta-1a plus remdesivir group and the placebo plus remdesivir group, with patients requiring high-flow oxygen at baseline having poorer outcomes after interferon beta-1a treatment.
LANCET RESPIRATORY MEDICINE
(2021)
Article
Public, Environmental & Occupational Health
Gabriela Paz-Bailey, Laura Adams, Joshua M. Wong, Katherine A. Poehling, Wilbur H. Chen, Veronica McNally, Robert L. Atmar, Stephen H. Waterman
Summary: Dengue is a vectorborne infectious disease caused by closely related dengue viruses, transmitted mainly by Aedes mosquitoes. The Dengvaxia vaccine is recommended by ACIP for children aged 9-16 with previous dengue infection in endemic areas, as it is safe and effective in preventing severe dengue. Prior natural infection is important, as vaccination may increase the risk of severe dengue in individuals experiencing their first natural infection after vaccination.
MMWR RECOMMENDATIONS AND REPORTS
(2021)
Article
Public, Environmental & Occupational Health
Mary J. Choi, Caitlin M. Cossaboom, Amy N. Whitesell, Jonathan W. Dyal, Allison Joyce, Rebecca L. Morgan, Doug Campos-Outcalt, Marissa Person, Elizabeth Ervin, Yon C. Yu, Pierre E. Rollin, Brian H. Harcourt, Robert L. Atmar, Beth P. Bell, Rita Helfand, Inger K. Damon, Sharon E. Frey
Summary: This report summarizes the recommendations for the use of the Ervebo Ebola vaccine in the United States, highlighting the contraindication for individuals with severe allergic reactions to rice protein. The vaccine is the first and only one licensed by the FDA for preventing EVD, with recommendations for preexposure vaccination for adults at highest risk.
MMWR RECOMMENDATIONS AND REPORTS
(2021)