Article
Biochemistry & Molecular Biology
Akachukwu Ibezim, Raphael Onuku, Chidalu Ottih, Ifeoma Ezeonu, Efeturi Onoabedje, Karuppasamy Ramanathan, Ngozi Nwodo
Summary: This study challenges the insusceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactam antibiotics by targeting penicillin binding protein 2a (PbP 2a). Computational strategies were employed to investigate the binding stability of two compounds with PbP 2a active and allosteric sites, and the results showed that these compounds can restore the susceptibility of certain MRSA isolates. Furthermore, the binding conformations of these compounds in PbP 2a were described, providing a rationale for structure-activity optimization.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Shu Wang, Ok-Hwa Kang, Dong-Yeul Kwon
Summary: The study demonstrates that plant-derived antimicrobial compound, TCA, significantly enhances the sensitivity of MRSA to conventional antibiotics by inhibiting specific gene and protein levels, especially showing efficacy against highly resistant biofilms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Jordy Evan Sulaiman, Lexin Long, Pei-Yuan Qian, Henry Lam
Summary: Elasnin not only exhibits excellent antibiofilm properties, but also shows antibacterial activity against growing methicillin-resistant Staphylococcus aureus (MRSA) planktonic cells. In this study, adaptive laboratory evolution (ALE) was applied to generate evolved strains with increased elasnin tolerance, which were found to be more sensitive toward daptomycin and lysostaphin. Whole-genome sequencing identified a single point mutation in a putative phosphate transport regulator in all evolved strains, resulting in increased intracellular phosphate and polyphosphate levels. Proteomics and transcriptomics analyses revealed the downregulation of proteins related to cell division, cell wall synthesis, fatty acid metabolism, glycolysis, the two-component system, RNA degradation, and ribosomal proteins following elasnin treatment. In contrast, transport proteins and proteins involved in oxidative phosphorylation and the phosphotransferase system were upregulated in the evolved strain, suggesting their importance in elasnin tolerance.
Article
Chemistry, Medicinal
Hamna Batool Hashmi, Muhammad Asad Farooq, Muhammad Hashim Khan, Abdulrahman Alshammari, Alanoud T. Aljasham, Sheikh Abdur Rashid, Nauman Rahim Khan, Irum Batool Hashmi, Muhammad Badar, Mohammad S. Mubarak
Summary: This study evaluated the efficacy of three fi-lactam drugs (meropenem, piperacillin, and tazobactam) alone and in combination against MRSA biofilms. The results showed that the combination of piperacillin and tazobactam exhibited the best removal effect on pre-formed MRSA biofilms.
Article
Infectious Diseases
Javier Campanini-Salinas, Juan Andrades-Lagos, Nicolas Hinojosa, Fabian Moreno, Pedro Alarcon, Gerardo Gonzalez-Rocha, Ian E. Burbulis, David Vasquez-Velasquez
Summary: New quinone compounds show promising inhibitory activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus, including clinical isolates. The compounds did not induce resistance in the clinical strains and were as effective as vancomycin in protecting larvae from MRSA infection. These quinone derivatives have potential as drug candidates for further development.
Article
Biochemistry & Molecular Biology
Abhishek Kumar Verma, Sk Faisal Ahmed, Md Shahadat Hossain, Ali Asger Bhojiya, Ankita Mathur, Sudhir K. Upadhyay, Abhishek K. Srivastava, Naveen Kumar Vishvakarma, Mayadhar Barik, Md Mizanur Rahaman, Newaz Mohammed Bahadur
Summary: This study aimed to find the best candidate drugs as inhibitors of Penicillin Binding Protein-2a for Methicillin-resistant Staphylococcus aureus (MRSA). The results showed that natural flavonoids have potential as adjuvant antimicrobial therapy against resistant strains, demonstrating good interactions in molecular docking and molecular dynamics simulations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Marta Woroszylo, Daria Ciecholewska-Jusko, Adam Junka, Radoslaw Drozd, Marcin Wardach, Pawel Migdal, Patrycja Szymczyk-Ziolkowska, Daniel Styburski, Karol Fijalkowski
Summary: The combination of rotating magnetic field (RMF) with beta-lactam antibiotics shows promising results in enhancing the antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA) by causing morphological alterations in bacterial cells. This study provides potential new treatment options for MRSA infections by utilizing the disruptive effect of RMF on bacterial cell walls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Infectious Diseases
Palanichamy Nandhini, Pradeep Kumar, Suresh Mickymaray, Abdulaziz S. Alothaim, Jayaprakash Somasundaram, Mariappan Rajan
Summary: Staphylococcus aureus is a harmful bacterium that becomes a superbug when it develops resistance to antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is a common superbug that presents challenges in treatment. Successful management of MRSA infection involves rapid identification of the infected site, susceptibility testing, evidence-based treatment, and preventive measures.
Article
Chemistry, Medicinal
Raj K. C. Hansa, M. M. K. Khan, M. M. Frangie, D. F. Gilmore, R. S. Shelton, A. Savenka, A. G. Basnakian, S. L. Shuttleworth, M. S. Smeltzer, M. A. Alam
Summary: A collection of potent antimicrobials has been synthesized and tested for antibacterial activity, showing low toxicity to human cells. Two compounds were highly effective against Staphylococcus aureus, with a low tendency for resistance development. In vivo mouse studies showed no harmful effects at doses up to 50 mg/kg.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Miguel Ribeiro, Sara Ceballos, Patricia Poeta, Carmen Torres, Gilberto Igrejas
Summary: A study using a proteomics approach revealed significant changes in protein expression in response to cefoxitin stress in MRSA, highlighting alterations in cellular metabolism, glycolysis, quorum sensing, and other functional pathways. These findings provide important insights for the treatment and research of MRSA and antibiotic resistance.
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
(2021)
Article
Public, Environmental & Occupational Health
Sara Quero, Marina Serras-Pujol, Noemi Parraga-Nino, Carmen Torres, Marian Navarro, Anna Vilamala, Emma Puigoriol, Javier Diez de los Rios, Elisenda Arque, Judit Serra-Pladevall, Alba Romero, Daniel Molina, Roger Paredes, Maria Luisa Pedro-Botet, Esteban Reynaga
Summary: This study investigated the prevalence of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) among workers in the pork production chain. The results showed that the prevalence of MRSA was high among workers in contact with live animals, especially in pig farms, livestock transporters, and slaughterhouses.
Review
Infectious Diseases
Sean N. Avedissian, Nathanial J. Rhodes, Christopher L. Shaffer, Lan Tran, John S. Bradley, Jennifer Le
Summary: MRSA remains a significant pathogen in children, with MRSA bacteremia closely associated with complications. Treatment options include vancomycin, oxazolidinones, semi-synthetic glycopeptides, daptomycin, tigecycline, novel cephalosporins, fosfomycin, and lefamulin, but limited data exist on usage in pediatric patients. Future studies are needed to ensure appropriate therapeutic treatment and outcomes, with phage therapy emerging as an investigational treatment option for deep-seated MRSA infections.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Stephanie Andrade, Maria J. Ramalho, Silvio B. Santos, Luis D. R. Melo, Rita S. Santos, Nuno Guimaraes, Nuno F. Azevedo, Joana A. Loureiro, Maria C. Pereira
Summary: Antimicrobial resistance (AMR) poses a significant threat to global health, with Methicillin-resistant Staphylococcus aureus (MRSA) being a major concern. Nanoparticles (NPs) have emerged as a promising approach for treating MRSA infections, acting as antibacterial agents or drug delivery systems. The targeted delivery of NPs to the infection site is crucial for effective treatment, allowing for high concentrations of therapeutics while minimizing toxicity to healthy cells and reducing AMR emergence and disruption of the healthy microbiota.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Karina M. S. Herrera, Gabriela F. M. Lopes, Michael E. Oliveira, Jaqueline F. Sousa, William G. Lima, Fernanda K. Silva, Julio C. M. Brito, Ana Julia P. S. Gomes, Gustavo H. R. Viana, Adriana C. Soares, Jaqueline M. S. Ferreira
Summary: This study evaluated the antibacterial activity of five 3-alkyl-pyridinic analogs against MRSA. Compound 6 showed promising antibacterial activity, exhibited a rapid bactericidal action, and had low resistance induction potential. It also showed an additive effect when combined with other antibiotics.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Marta Woroszylo, Daria Ciecholewska-Jusko, Adam Junka, Marcin Wardach, Grzegorz Chodaczek, Bartlomiej Dudek, Karol Fijalkowski
Summary: This study analyzed the impact of combining rotating magnetic field (RMF) with various classes of antibiotics on nine strains of Staphylococcus aureus. The results showed that combining RMF with antibiotics that interfere with cell walls, particularly beta-lactams, led to favorable changes in growth inhibition zones or minimal inhibitory concentration values, especially for methicillin-resistant strains. The study suggests that the application of magnetic fields could be an important strategy in combating infections caused by methicillin-resistant staphylococci due to the increased effectiveness of antibiotics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kiran V. Mahasenan, Maria T. Batuecas, Stefania De Benedetti, Choon Kim, Neha Rana, Mijoon Lee, Dusan Hesek, Jed F. Fisher, Julia Sanz-Aparicio, Juan A. Hermoso, Shahriar Mobashery
ACS CHEMICAL BIOLOGY
(2020)
Article
Cell Biology
Trung T. Nguyen, Jeffrey I. Jones, William R. Wolter, Rocio L. Perez, Valerie A. Schroeder, Matthew M. Champion, Dusan Hesek, Mijoon Lee, Mark A. Suckow, Shahriar Mobashery, Mayland Chang
WOUND REPAIR AND REGENERATION
(2020)
Article
Multidisciplinary Sciences
Kyungjin Min, Doo Ri An, Hye-Jin Yoon, Neha Rana, Ji Su Park, Jinshil Kim, Mijoon Lee, Dusan Hesek, Sangryeol Ryu, B. Moon Kim, Shahriar Mobashery, Se Won Suh, Hyung Ho Lee
NATURE COMMUNICATIONS
(2020)
Article
Microbiology
Katelyn E. Carothers, Zhong Liang, Jeffrey Mayfield, Deborah L. Donahue, Mijoon Lee, Bill Boggess, Victoria A. Ploplis, Francis J. Castellino, Shaun W. Lee
JOURNAL OF BACTERIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Richard T. Cattley, Mijoon Lee, William C. Boggess, William F. Hawse
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Tietao Wang, Zhaoyu Hu, Xiao Du, Yue Shi, Jing Dang, Mijoon Lee, Dusan Hesek, Shahriar Mobashery, Min Wu, Haihua Liang
MOLECULAR MICROBIOLOGY
(2020)
Article
Chemistry, Medicinal
Nichole K. Stewart, Marta Toth, Anastasiya Stasyuk, Mijoon Lee, Clyde A. Smith, Sergei B. Vakulenko
Summary: Avibactam is a potent irreversible mechanism-based inhibitor of class A and C beta-lactamases, with variable activity against some class D enzymes from Gram-negative bacteria. The interaction of avibactam with recently discovered class D beta-lactamases from Gram-positive bacteria has not been studied. X-ray crystallographic studies demonstrate the rapid formation of a stable CDD-1-avibactam acyl-enzyme complex and differences in anchoring of the inhibitor by class D enzymes from Gram-positive and Gram-negative bacteria.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Vijay Kumar, Snigdha A. Mathure, Mijoon Lee, Jacob Boorman, Ximin Zeng, Jun Lin, Dusan Hesek, Elena Lastochkin, Shahriar Mobashery, Focco van den Akker
Summary: Cj0843c, a soluble lytic transglycosylase from Campylobacter jejuni, has both exolytic and endolytic activities and shows a preference for substrates with anhMurNAc ends and peptide stems. Mutation studies revealed the critical roles of catalytic E390, as well as R388 and K505 in the positively charged pocket. Interestingly, positively charged residues in the pocket play different roles in binding the predominantly negatively charged PG. X-ray crystallography and molecular dynamics simulations demonstrated that the active site of Cj0843c can bind GlcNAc containing di- and trisaccharides without MurNAc moieties, peptide stems, and anhMurNAc ends.
Article
Biochemistry & Molecular Biology
Siseth Martinez-Caballero, Kiran Mahasenan, Choon Kim, Rafael Molina, Rhona Feltzer, Mijoon Lee, Renee Bouley, Dusan Hesek, Jed F. Fisher, Ines G. Munoz, Mayland Chang, Shahriar Mobashery, Juan A. Hermoso
Summary: This study provides a comprehensive analysis of the structure and function of Staphylococcus aureus PBP1, revealing important mechanistic insights into its role in cell division. The research highlights the mobility and interaction of the PASTA domains in coordination with other domains, shedding light on the coordination of transpeptidation and polymerization processes in bacterial divisome.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
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
Biochemistry & Molecular Biology
Douglas S. Prado, Richard T. Cattley, Corey W. Shipman, Cassandra Happe, Mijoon Lee, William C. Boggess, Matthew L. MacDonald, William F. Hawse
Summary: CD4+ T cells differentiate into Th17 and Treg cells, which are regulated by different signaling pathways including TCR, TGF-beta R, and IL-6R signals. The study found that Treg induction promotes the formation of the SMAD3/4 trimer through SMAD3-mediated TGF-beta R signaling, suppressing TCR signaling, while Th17 induction inhibits the formation of the SMAD3/4 trimer by activating STAT3, leading to elevated TCR and PI3K signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Microbiology
Thomas E. Smith, Mijoon Lee, Maria D. Person, Dusan Hesek, Shahriar Mobashery, Nancy A. Moran
Summary: Enzymes can undergo shifts in preferred substrates or catalytic activities during evolution, and the function of enzymes may change following horizontal gene transfer, especially for bacterial genes that have moved to animal genomes. Some insects have acquired genes encoding enzymes for bacterial cell wall components, which appear to play a role in influencing bacterial cell wall metabolism.
Article
Biochemistry & Molecular Biology
James Hentig, Leah J. Campbell, Kaylee Cloghessy, Mijoon Lee, William Boggess, David R. Hyde
Summary: Approximately 2 million individuals experience traumatic brain injury (TBI) each year in the United States. Post-traumatic seizures (PTS) are a common and difficult to treat complication in TBI patients. The Sonic hedgehog signaling pathway may play a role in regulating glutamate excitotoxicity and TBI sequelae.
Meeting Abstract
Biochemistry & Molecular Biology
Focco van den Akker, Vijay Kumar, Snigdha Mathure, Mijoon Lee, Jacob Boorman, Ximin Zeng, Jun Lin, Dusan Hesek, Shahriar Mobashery
Article
Chemistry, Medicinal
Zhihong Peng, Trung T. Nguyen, Wei Song, Bowen Anderson, William R. Wolter, Valerie A. Schroeder, Dusan Hesek, Mijoon Lee, Shahriar Mobashery, Mayland Chang
Summary: DFUs, common complication of diabetes, are difficult to heal due to persistent inflammation. Infection control with antibiotics is necessary before treatment of the wound. MMPs play roles in the pathology and repair of DFUs, with active MMP-9 levels found to prevent diabetic wounds from healing. The small-molecule MMP-9 inhibitor (R)-ND-336 shows efficacy in improving wound healing by inhibiting MMP-9 and reducing inflammation.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)