Article
Chemistry, Multidisciplinary
Shakilur Rahman, Subham Nath, Utpal Mohan, Amit Kumar Das
Summary: This study evaluates FDA-approved drugs that can be repurposed against Staphylococcus aureus infection. The results show that Lumacaftor has high affinity, moderate bactericidal activity, and biofilm inhibition potential, making it a potential lead molecule against S. aureus.
Article
Microbiology
Nidhi Satishkumar, Li-Yin Lai, Nagaraja Mukkayyan, Bruce E. Vogel, Som S. Chatterjee
Summary: This study demonstrates that PBP4 is an important mediator of beta-lactam resistance not only in methicillin-susceptible Staphylococcus aureus (MSSA) strains but also in MRSA strains. When present together, overexpression of PBP2a and PBP4 can lead to increased beta-lactam resistance, causing treatment complications. Monitoring PBP4-associated resistance in clinical settings and understanding the mechanistic basis of this resistance are important for developing targeted treatments. Additionally, strains with increased PBP4 expression are less pathogenic, indicating a potential trade-off between beta-lactam resistance and virulence.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Michael Hort, Ute Bertsche, Senada Nozinovic, Alina Dietrich, Anne Sophie Schroetter, Laura Mildenberger, Katharina Axtmann, Anne Berscheid, Gabriele Bierbaum
Summary: The study analyzed the cell wall structures of several laboratory vancomycin-intermediate S. aureus strains and found that alterations in cell wall architecture play a crucial role in vancomycin resistance. Changes in wall teichoic acids impact autolysis and vancomycin susceptibility. A novel connection between wall teichoic acids, autolysis, and vancomycin resistance in S. aureus was identified.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
George Sakoulas, Victor Nizet
Summary: Standard methods of susceptibility testing in bacteriological media have significant shortcomings, as the media does not replicate the in vivo environment and fails to capture sub-MIC effects on bacterial virulence properties. Attempts to determine the quantitative relevance of beta-lactam MIC in Staphylococcus aureus infections using current clinical microbiology standards are likely to be unsuccessful until testing conditions better mimic the in vivo environment.
JOURNAL OF CLINICAL MICROBIOLOGY
(2023)
Article
Infectious Diseases
Won-Sik Yeo, Bohyun Jeong, Nimat Ullah, Majid Ali Shah, Amjad Ali, Kyeong Kyu Kim, Taeok Bae
Summary: FtsH plays a critical role in bacterial virulence and stress resistance in Staphylococcus aureus, sensitizing MRSA to beta-lactam antibiotics by degrading YpfP which synthesizes the anchor molecule for LTA. Overexpression of FtsH or disruption of ypfP increased sensitivity to beta-lactams, while knockout mutations in ftsH and ypfP led to thicker cell walls. The beta-lactam sensitization is associated with production of larger LTA molecules, and YpfP may be a potential target for novel anti-MRSA drugs.
Article
Microbiology
Qiang Ma, Guilai Wang, Na Li, Xin Wang, Xinyun Kang, Yanni Mao, Guiqin Wang
Summary: Andrographolide (AP), a natural active compound, restores the susceptibility of MRSA to beta-lactam antibiotics by inhibiting beta-lactamase BlaZ, downregulating the expression of critical resistance genes, disrupting cell wall homeostasis, and increasing peptidoglycan synthesis.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Delphine Coupri, Nicolas Verneuil, Axel Hartke, Axelle Liebaut, Thierry Lequeux, Emmanuel Pfund, Aurelie Budin-Verneuil
Summary: The study investigates the potential of targeting D-alanylation of teichoic acids (TAs) mediated by the dlt operon gene products as a strategy to overcome beta-lactam resistance in MRSA. Results show that genetic or chemical inhibition of the Dlt system can resensitize MRSA to beta-lactam antibiotics, especially in combination with imipenem, offering a promising therapeutic approach for combating MRSA infections.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Microbiology
Natalia Kurepina, Liang Chen, Kaelea Composto, Dalin Rifat, Eric L. Nuermberger, Barry N. Kreiswirth
Summary: In this study, we used CRISPRi assay to control the gene expressions of pbpB and cwIM in Mycobacterium abscessus and evaluated their contribution to beta-lactam susceptibility. Our results demonstrated that CRISPRi can be used as an experimental approach to study drug/target interactions in M. abscessus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(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
Microbiology
Joshua A. F. Sutton, Oliver T. Carnell, Lucia Lafage, Joe Gray, Jacob Biboy, Josie F. Gibson, Eric J. G. Pollitt, Simone C. Tazoll, William Turnbull, Natalia H. Hajdamowicz, Bartlomiej Salamaga, Grace R. Pidwill, Alison M. Condliffe, Stephen A. Renshaw, Waldemar Vollmer, Simon J. Foster
Summary: Peptidoglycan is a crucial component of Staphylococcus aureus cell wall, and its structure and dynamics during infection are not well understood. By isolating bacteria from active infections, researchers found that thicker cell walls and reduced peptidoglycan crosslinking in ex vivo cells may play a role in disease. Specific proteins involved in peptidoglycan synthesis and degradation, such as PBP4 and SagB, impact the pathogen's fitness and survival within host cells. These findings highlight the importance of understanding cell wall structure and dynamics for pathogenesis and disease control strategies.
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.
Article
Microbiology
Elizabeth V. K. Ledger, Andrew M. Edwards
Summary: Most bactericidal drugs require bacterial replication and/or metabolic activity for their killing activity, but the lipopeptide antibiotic daptomycin has been reported to efficiently kill growth-arrested bacteria. However, a prolonged growth arrest can lead to daptomycin tolerance in Staphylococcus aureus, requiring glucose and increased production of certain cell wall polymers. This active cell wall remodelling sets daptomycin tolerance apart from other forms of antibiotic tolerance in nonreplicating bacteria.
Article
Biotechnology & Applied Microbiology
Nicolas Ripari, Ana Flavia Marques Pereira, Ary Fernandes Junior, Vera Lucia Mores Rall, Jennyfer A. Aldana-Mejia, Jairo Kenupp Bastos, Jose Mauricio Sforcin
Summary: The antibacterial activity of red and brown propolis extracts, as well as their synergistic effects with cefoxitin, imipenem, and ertapenem, were evaluated against MRSA strains. The results showed that the combination of red propolis extract and imipenem had the strongest inhibitory effect and the greatest impact on biofilm formation and membrane conductivity. Computational analyses suggested that the constituents of red propolis extract may interact with PBP2a.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiaoduo Li, Zhengcai Ma, Qin Tang, Zhenwei Gui, Biao Zhang, Guang Sun, Jingwei Li, Juan Li, Mengmeng Li, Xuegang Li, Hang Ma, Xiaoli Ye
Summary: This research uncovered the antimicrobial properties of a novel compound called 8-octyl berberine (OBBR) against Staphylococcus aureus. OBBR showed promising results with minimum inhibitory concentration (MIC) similar to levofloxacin, but with lower chances of inducing resistance. Mechanistically, OBBR induced morphological alterations in the bacteria, disrupted the bacterial cell wall and membrane, and inhibited the enzymatic activity of the protein MraY, ultimately inhibiting peptidoglycan synthesis. OBBR emerges as a potential alternative antibiotic against S. aureus with limited drug resistance development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Lorina Badger-Emeka, Promise Madu Emeka, Hairul Islam M. Ibrahim
Summary: This study evaluated the synergistic effects of Nigella sativa with beta-lactam antibiotics on MRSA isolates, showing inhibition and significant differences in antimicrobial susceptibility and time-kill assays. Results from SEM and TEM revealed cell wall disruption as the mechanism of action leading to bacterial lysis.
APPLIED SCIENCES-BASEL
(2021)
Article
Immunology
Hong Zhang, Libo Zheng, Dermot P. B. McGovern, Ariel M. Hamill, Ryan Ichikawa, Yoshitake Kanazawa, Justin Luu, Kotaro Kumagai, Marianne Cilluffo, Masayuki Fukata, Stephan R. Targan, David M. Underhill, Xiaolan Zhang, David Q. Shih
JOURNAL OF IMMUNOLOGY
(2017)
Article
Microbiology
Joseph H. Skalski, Jose J. Limon, Purnima Sharma, Matthew D. Gargus, Christopher Nguyen, Jie Tang, Ana Lucia Coelho, Cory M. Hogaboam, Timothy R. Crother, David M. Underhill
Review
Gastroenterology & Hepatology
Jose J. Limon, Kathleen M. Kershaw, David M. Underhill
CURRENT OPINION IN GASTROENTEROLOGY
(2018)
Article
Microbiology
Jose J. Limon, Jie Tang, Dalin Li, Andrea J. Wolf, Kathrin S. Michelsen, Vince Funari, Matthew Gargus, Christopher Nguyen, Purnima Sharma, Viviana Maymi, Iliyan D. Iliev, Joseph H. Skalski, Jordan Brown, Carol Landers, James Borneman, Jonathan Braun, Stephan R. Targan, Dermot Pb McGovern, David M. Underhill
CELL HOST & MICROBE
(2019)
Article
Cell Biology
Andrea J. Wolf, Jose J. Limon, Christopher Nguyen, Alexander Prince, Anthony Castro, David M. Underhill
Summary: Malassezia spp. yeasts are commonly found on mammalian skin, but can also be found in the intestines in certain diseases. They induce inflammatory responses by activating proinflammatory cytokine production, mainly through the Dectin2 and CARD9 signaling pathways, and stimulate NLRP3 inflammasome activation.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Umang Jain, Aaron M. Ver Heul, Shanshan Xiong, Martin H. Gregory, Elora G. Demers, Justin T. Kern, Chin-Wen Lai, Brian D. Muegge, Derek A. G. Barisas, J. Steven Leal-Ekman, Parakkal Deepak, Matthew A. Ciorba, Ta-Chiang Liu, Deborah A. Hogan, Philip Debbas, Jonathan Braun, Dermot P. B. McGovern, David M. Underhill, Thaddeus S. Stappenbeck
Summary: The study revealed that Debaryomyces hansenii fungus inhabits incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD patients, impairing colonic healing. Mechanistically, D. hansenii affects mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis.
Article
Cell Biology
Seeun Oh, Kai Li, Alexander Prince, Matthew L. Wheeler, Hussein Hamade, Christopher Nguyen, Kathrin S. Michelsen, David M. Underhill
Summary: Dectin-1 recognizes beta-glucan in fungal cell walls, and the size of the target influences dendritic cell activation and cytokine production, leading to differentiation of T helper cell subsets.
Article
Immunology
Sung Hoon Baik, V. Krishnan Ramanujan, Courtney Becker, Sarah Fett, David M. Underhill, Andrea J. Wolf
Summary: NLRP3 inflammasome activation is a highly regulated process that controls the release of inflammatory cytokines IL-1 beta and IL-18 during various infections and diseases. The activation involves the dissociation of the glycolytic enzyme hexokinase 2 from the voltage-dependent anion channel (VDAC) in mitochondria, leading to calcium release from the ER and calcium influx into mitochondria. This influx triggers the oligomerization of VDAC, allowing proteins and mitochondrial DNA to exit the mitochondria and associate with NLRP3 during inflammasome assembly.
SCIENCE IMMUNOLOGY
(2023)
Review
Medicine, Research & Experimental
David M. Underhill, Jonathan Braun
Summary: The gut microbiome, specifically the fungal community, plays a crucial role in the development and progression of inflammatory bowel disease (IBD). Recent studies have identified a strong association between certain fungal taxa and the cellular and molecular pathways of IBD. Furthermore, it has been found that disease-contributing bacteria and fungi may interact indirectly through their fungal-bacterial ecological interactions. These insights and research strategies provide a foundation for including the fungal community in both basic and translational IBD research.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Immunology
Andrea J. Wolf, David M. Underhill
NATURE REVIEWS IMMUNOLOGY
(2018)
Review
Microbiology
Marissa J. Paterson, Seeun Oh, David M. Underhill
CURRENT OPINION IN MICROBIOLOGY
(2017)
Article
Microbiology
Marisel Sanchez, Stacey L. Kolar, Sabrina Mueller, Christopher N. Reyes, Andrea J. Wolf, Chihiro Ogawa, Rajat Singhania, Daniel D. De Carvalho, Moshe Arditi, David M. Underhill, Gislaine A. Martins, George Y. Liu
CELL HOST & MICROBE
(2017)
Review
Microbiology
Jose J. Limon, Joseph H. Skalski, David M. Underhill
CELL HOST & MICROBE
(2017)
Review
Oncology
A. Lenore Ackerman, David M. Underhill
ANNALS OF TRANSLATIONAL MEDICINE
(2017)
