Article
Infectious Diseases
Nidhi Satishkumar, J. Andrew N. Alexander, Raymond Poon, Emma Buggeln, Maria A. Argudin, Natalie C. J. Strynadka, Som S. Chatterjee
Summary: The study showed that mutations associated with the pbp4 promoter and pbp4 gene altered protein activity and mediated beta-Lactam resistance among clinically isolated strains of Staphylococcus aureus.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Artur Sargun, Timothy C. Johnstone, Hui Zhi, Manuela Raffatellu, Elizabeth M. Nolan
Summary: This study presents the synthesis and evaluation of siderophore-beta-lactam conjugates with enhanced activity against Escherichia coli, particularly highlighting the advantages of the DGE-Mem conjugate. The findings provide insights into the uptake and cell-killing activity of these conjugates and their potential for narrowing the activity spectrum of antibiotics in clinical use.
Article
Infectious Diseases
Anouk E. Muller, Marie Attwood, Sanne Van den Berg, Rajesh Chavan, Hariharan Periasamy, Alan Noel, Alasdair MacGowan
Summary: This study identified the pharmacodynamic targets of cefepime using both in vivo and in vitro models, and found that cefepime has lower requirements compared to other cephalosporins, possibly due to its better permeation properties and enhanced bactericidal action driven by multiple PBP affinities.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Zhe Ji, Steven G. Boxer
Summary: Enzyme active sites can regulate the hydrolysis of covalent bonds through electric fields, affecting the development and overcoming of resistance. Over billions of years of evolution, the change in electric fields has increased the hydrolysis rate of covalent bonds by 5 orders of magnitude, a trend that continues in current antibiotic drug development. The electric field can be used as a unified physical metric to understand protein evolution and guide drug design.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Akiko Hisada, Erino Matsumoto, Ryo Hirano, Mami Konomi, Jacques Yaacoub Bou Khalil, Didier Raoult, Yusuke Ominami
Summary: Rapid determination of drug efficacy against bacterial pathogens is crucial for detecting potentially resistant bacteria and optimizing the use of antimicrobials. This study proposes a simplified method for assessing antimicrobial efficacy by detecting immediate damage to bacterial cells using tabletop SEM. The method involves staining unaffected bacterial cell envelopes and whole affected cells, with brighter images indicating lethal damage. By quantifying single-cell images based on brightness, the efficacy of antimicrobials in causing bacterial-cell-envelope damage can be determined.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Helle Brander Eriksen, Kurt Fuursted, Anders Jensen, Christian Salgard Jensen, Xiaohui Nielsen, Jens Jorgen Christensen, Patricia Shewmaker, Ana Rita Rebelo, Frank Moller Aarestrup, Kristian Schonning, Hans-Christian Slotved
Summary: The susceptibility of Streptococcus pneumoniae to beta-lactam drugs can be predicted from the amino acid sequence of penicillin-binding proteins (PBPs). A BLAST analysis can accurately predict the susceptibility of Danish S. pneumoniae isolates and some internationally collected MGS isolates. However, the current database is not effective in predicting the susceptibility of other MGS strains.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Infectious Diseases
Mitsuyo Kawaguchiya, Noriko Urushibara, Meiji Soe Aung, Kenji Kudo, Masahiko Ito, Satoshi Habadera, Nobumichi Kobayashi
Summary: This study identified novel penicillin binding protein (PBP) profiles and mutations associated with penicillin nonsusceptibility in nonencapsulated Streptococcus pneumoniae (NESp). The results revealed that the PBP profiles 13-16-ne1 and 13-7-ne4, as well as PBP1a type-13 and-131, PBP2b type-7,-ne1, and-ne2 were closely associated with penicillin nonsusceptibility in NESp.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Gianluca Morroni, Simona Fioriti, Federica Salari, Andrea Brenciani, Lucia Brescini, Marina Mingoia, Eleonora Giovanetti, Antonella Pocognoli, Andrea Giacometti, Elisa Molinelli, Annamaria Offidani, Oriana Simonetti, Oscar Cirioni
Summary: The study revealed that ceftaroline non-susceptible MRSA isolates were found in the most common ST228 clone in Italy, as well as in the ST22 clone, confirming the increasing role of these clones in hospital infections.
Article
Microbiology
Shannon G. Murphy, Andrew N. Murtha, Ziyi Zhao, Laura Alvarez, Peter Diebold, Jung-Ho Shin, Michael S. VanNieuwenhze, Felipe Cava, Tobias Doerr
Summary: In Vibrio cholerae, endopeptidases are essential for proper cell elongation and division, while aPBPs become crucial for maintaining structural integrity during endopeptidase insufficiency, and the Rod system remains active but contributes minimally to cell expansion under these conditions.
Article
Multidisciplinary Sciences
Michael D. Sacco, Shaohui Wang, Swamy R. Adapa, Xiujun Zhang, Eric M. Lewandowski, Maura Gongora, Dimitra Keramisanou, Zachary D. Atlas, Julia A. Townsend, Jean R. Gatdula, Ryan T. Morgan, Lauren R. Hammond, Michael T. Marty, Jun Wang, Prahathees J. Eswara, Ioannis Gelis, Rays H. Y. Jiang, Xingmin Sun, Yu Chen
Summary: β-lactam antibiotics inhibit bacterial cell wall synthesis by targeting PBPs. This study reveals the unique structural features of PBPs in C. difficile and sheds light on the mechanisms underlying beta-lactam resistance in this pathogen, providing new insights for the treatment of Clostridioides difficile infection.
NATURE COMMUNICATIONS
(2022)
Article
Infectious Diseases
Kamonwan Lunha, Wiyada Chumpol, Surasak Jiemsup, Sukuma Samngamnim, Pornchalit Assavacheep, Suganya Yongkiettrakul
Summary: The study aims to investigate the genetic basis for the decrease in susceptibility to penicillin and other beta-lactams among Streptococcus suis. The findings suggest a growing trend of reduced susceptibility to beta-lactams and the presence of substitutions within penicillin-binding proteins (PBPs) associated with this decrease. The study highlights the importance of genetic mutations in mediating antibiotic resistance in S. suis.
Article
Microbiology
Marta Toth, Mijoon Lee, Nichole K. Stewart, Sergei B. Vakulenko
Summary: Resistance to beta-lactams is a major problem in treating bacterial infections. In the case of Acinetobacter baumannii, resistance to beta-lactam antibiotics has resulted in the spread of multidrug-resistant isolates. This study found that PBP3 is essential for the survival of A. baumannii, and inhibiting PBP1a and PBP2, or PBPs in combination with LdtJ, could be potential strategies for designing new drugs against this pathogen.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Claretta J. J. Sullivan, Kennedy Brown, Chia-Suei Hung, Joseph Kuo-Hsiang Tang, Mark DeSimone, Vincent Chen, Pamela F. F. Lloyd, Maneesh Gupta, Abby Juhl, Wendy Crookes-Goodson, Milana Vasudev, Patrick B. B. Dennis, Nancy Kelley-Loughnane
Summary: Nature provides examples of materials with exceptional properties due to hierarchical assembly. This study demonstrates the potential of using Cellulophaga lytica bacteria for large-scale biomanufacturing of ordered materials, overcoming current challenges in industrial production.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Caroline Midonet, Sean Bisset, Irina Shlosman, Felipe Cava, David Z. Rudner, Thomas G. Bernhardt
Summary: The peptidoglycan layer protects bacteria and defines their shape. How class A penicillin-binding proteins (aPBPs) are controlled in Gram-positive bacteria is unclear. MacP, a regulator in Streptococcus pneumoniae, promotes PG polymerization by altering the TM-polymerase domain interface in PBP2a. Proper aPBP regulation is important for cell morphogenesis.
Article
Microbiology
Katarzyna Wacnik, Vincenzo A. Rao, Xinyue Chen, Lucia Lafage, Manuel Pazos, Simon Booth, Waldemar Vollmer, Jamie K. Hobbs, Richard J. Lewis, Simon J. Foster
Summary: Bacterial cell wall peptidoglycan synthesis is essential for bacterial growth and division and is targeted by clinically important antibiotics. Staphylococcus aureus, a human pathogen, has only two essential penicillin-binding proteins (PBPs) that are required for growth and division. Our recent studies have revealed a complex peptidoglycan architecture in S. aureus during division. PBP1 plays multiple essential roles in cell division, both as an enzyme and as a regulator.