Article
Biochemistry & Molecular Biology
Yawen Gao, Hongsu Wang, Xuening Li, Xiaodi Niu
Summary: Through virtual screening and in vitro bioactivity assays, (-)-epicatechin gallate (ECG), a polyphenol compound from green tea, was found to exhibit significant anti-Ser/Thr phosphatase (Stp1) activity against Staphylococcus aureus (S. aureus). ECG targeted S. aureus Stp1, preventing virulence gene up-regulation and antibody membrane formation, and protected mice from S. aureus infection. Molecular dynamics simulation revealed the allosteric inhibitory mechanism of ECG on Stp1.
Article
Biochemistry & Molecular Biology
Pranabesh Mandal, Priyanka Rani, Girish Chandra, Durg Vijay Singh
Summary: This study investigates the resistance development of glycopeptide antibiotics vancomycin and daptomycin in treating Gram-positive staphylococcal infections. A protein called Stp1, which is involved in the phospho-signaling system of bacterial cell wall formation, was found to have an important role in substrate regulation. Molecular dynamics simulations were used to sample the flap sub-domain of Stp1 and revealed its greater flexibility compared to other parts of the structure. The findings suggest potential implications for structure-based antibiotics discovery.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Markus Huemer, Srikanth Mairpady Shambat, Sanne Hertegonne, Judith Bergada-Pijuan, Chun-Chi Chang, Sandro Pereira, Alejandro Gomez-Mejia, Lies Van Gestel, Julian Bar, Clement Vulin, Sibylle Pfammatter, Timothy P. Stinear, Ian R. Monk, Jonathan Dworkin, Annelies S. Zinkernagel
Summary: Staphylococcus aureus infections are difficult to treat due to the occurrence of persister cells that are metabolically quiescent and tolerant to antibiotics. Acid stress-mimicking conditions in the host tissues can delay bacterial growth and alter the serine and threonine phosphoproteome, including increased phosphorylation of PknB. Deletion of stp, the only annotated serine-threonine phosphatase in S. aureus, exacerbates the growth delay and phenotypic heterogeneity under different stress challenges. This study highlights the importance of phosphoregulation in bacterial quiescence and antibiotic tolerance, suggesting potential therapeutic strategies targeting PknB or Stp to prevent persister formation in S. aureus infections.
Article
Pharmacology & Pharmacy
Yanan Yang, Xiyan Wang, Yawen Gao, Hongsu Wang, Xiaodi Niu
Summary: The eukaryotic-like serine/threonine phosphatase (Stp1) is an enzyme-dependent protein phosphatase involved in regulating various virulence factors of Staphylococcus aureus, and has been identified as a potential target for antibiotic development. Through virtual screening, a potent and effective Stp1 inhibitor, verbascoside (VBS), has been discovered. VBS exerts its inhibitory effects on Stp1 through both competitive and allosteric mechanisms, with specific binding residues identified in the enzyme.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Infectious Diseases
Jasmina Al Janabi, Staffan Tevell, Raphael Niklaus Sieber, Marc Stegger, Bo Soderquist
Summary: This study investigated the susceptibility of Staphylococcus epidermidis strains from prosthetic joint infections to dalbavancin and the genomic variation in strains with reduced susceptibility. The results suggest that exposure to dalbavancin may lead to reduced susceptibility through selection of pre-existing subpopulations, epigenetic changes, or spontaneous mutations during antibiotic exposure. Therefore, source control and adequate antibiotic concentrations are important to prevent emerging reduced susceptibility during dalbavancin treatment.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Nour Ahmad-Mansour, Mohamed Ibrahem Elhawy, Sylvaine Huc-Brandt, Nadhuma Youssouf, Linda Paetzold, Marianne Martin, Noran Abdel-Wadood, Ahmad Aljohmani, Madjid Morsli, Gabriela Krasteva-Christ, Soeren L. Becker, Daniela Yildiz, Jean-Philippe Lavigne, Laila Gannoun-Zaki, Markus Bischoff, Virginie Molle
Summary: This study demonstrates that the acid phosphatase SapS plays a significant role in Staphylococcus aureus infection by promoting intracellular survival in macrophages, inhibiting host immune responses, and influencing the bacterium's adaptation to oxidative stress. The SA564 sapS mutant shows reduced bacterial burden and pathogenicity in animal models, indicating the importance of SapS in virulence. Overall, this research provides new insights into the immune evasion mechanisms of S. aureus and highlights the potential of targeting SapS for the development of therapeutic strategies against this pathogen.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Hae-Sun Chung, Miae Lee
Summary: The methods and results obtained using commercialized automation systems for antimicrobial susceptibility testing are inconsistent. This study evaluated different testing methods and found that BMD and Etest were more reliable compared to VITEK2, Sensititre, Phoenix, and MicroScan in determining vancomycin susceptibility and minimum inhibitory concentration for SA-RVS.
Article
Chemistry, Multidisciplinary
Payton M. Thomas, Margaret A. Deming, Aurijit Sarkar
Summary: The fi-lactamase enzyme renders early fi-lactam antibiotics ineffective against MRSA, but penicillin G can overcome this resistance by blocking the activity of fi-lactamase. This article presents a method using pyrimidine-2-amines (P2As) to reduce the activity of fi-lactamase, enhancing the effectiveness of penicillin G against MRSA without directly inhibiting the enzyme.
Article
Biochemistry & Molecular Biology
Natalia Stach, Abdulkarim Karim, Przemyslaw Golik, Radoslaw Kitel, Katarzyna Pustelny, Natalia Gruba, Katarzyna Groborz, Urszula Jankowska, Sylwia Kedracka-Krok, Benedykt Wladyka, Marcin Drag, Adam Lesner, Grzegorz Dubin
Summary: By studying the substrate specificity and structure of SplF, it was found that the enzyme has a strict preference for long aliphatic sidechains at the P1 subsite and significant selectivity for aromatic residues at P3, with its crystal structure defining the structural basis of this substrate specificity. Comparisons with other Spl proteases suggest that the spl operon encodes a unique extracellular proteolytic system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yifan Rao, Huagang Peng, Weilong Shang, Zhen Hu, Yi Yang, Li Tan, Ming Li, Renjie Zhou, Xiancai Rao
Summary: The WalK(S221P) mutation enhances vancomycin resistance and decreases virulence in Staphylococcus aureus.
JOURNAL OF ADVANCED RESEARCH
(2022)
Review
Parasitology
Jenny Nancy Gomez-Sandoval, Alma Reyna Escalona-Montano, Abril Navarrete-Mena, M. Magdalena Aguirre-Garcia
Summary: Protein phosphatases in parasites exhibit diverse functions and characteristics, some of which could serve as potential targets for therapy or diagnostic markers. Understanding their involvement in parasite cell cycle, metabolism, virulence, and immune response evasion is crucial for medical and veterinary purposes.
PARASITOLOGY RESEARCH
(2021)
Article
Microbiology
Yi Li, Fengli Zhu, Adhar C. Manna, Liang Chen, Jason Jiang, Jong-In Hong, Richard A. Proctor, Arnold S. Bayer, Ambrose L. Cheung, Yan Q. Q. Xiong
Summary: Persistent endovascular infections caused by MRSA strains susceptible to anti-MRSA antibiotics represent a unique variant of antibiotic resistance mechanisms and a significant therapeutic challenge. Prophage, a mobile genetic element carried by MRSA isolates, provides metabolic advantages and resistance mechanisms to bacterial hosts. This study demonstrates that the gp05 gene of the novel prophage & phi;SA169 significantly impacts MRSA virulence factors, host immune responses, and vancomycin treatment efficacy, leading to persistent outcomes in MRSA endovascular infection.
MICROBIOLOGY SPECTRUM
(2023)
Article
Pharmacology & Pharmacy
Mengli Jin, Shuyue Zhu, Yating Tang, Xiangri Kong, Xingye Wang, Yufen Li, Shuang Jiang, Lin Wei, Chunjie Hu, Bingmei Wang, Wu Song
Summary: Antimicrobial resistance (AMR) is a global health threat, and there is a need for new anti-infective agents. Ayanin, a flavonoid extracted from Callicarpa nudiflora, was found to be an inhibitor of MRSA ClpP, suggesting its potential therapeutic effect against MRSA infections.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Nadine Prust, Saar van der Laarse, Henk van den Toorn, Nina M. van Sorge, Simone Lemeer
Summary: This study utilized an optimized protocol for efficient phosphopeptide enrichment and LC-MS/MS to investigate protein phosphorylation in Staphylococcus aureus, resulting in a comprehensive phosphoproteome dataset that sheds light on signaling pathways in bacteria. The research significantly increased the number of phosphosite identifications compared to previous studies and identified downstream targets of a key Ser/Thr kinase in S. aureus, indicating a greater abundance of Ser/Thr kinase signaling in this bacterium.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Review
Infectious Diseases
Mohammad Ejaz, Muhammad Ali Syed, Charlene R. Jackson, Mehmoona Sharif, Rani Faryal
Summary: Staphylococcus aureus is a multidrug-resistant pathogen, with vancomycin often used as the last resort treatment for infections. However, overuse and misuse of vancomycin have led to resistance among S. aureus strains. South Asia, with its large population and limited healthcare infrastructure, is prone to the emergence of antibiotic resistance. This article briefly discusses the mechanism of vancomycin resistance, its emergence in S. aureus, and the molecular epidemiology of non-susceptible S. aureus to vancomycin in the South Asian region.
Review
Infectious Diseases
Kelly A. Cairns, Iain J. Abbott, Michael J. Dooley, Anton Y. Peleg, Trisha N. Peel, Andrew A. Udy
Summary: This study aimed to determine whether daptomycin therapeutic drug monitoring (TDM), including dose adjustment, improves the clinical outcomes of adult patients with Gram-positive infections. A systematic review found no studies exploring the efficacy of routine daptomycin TDM in comparison with fixed dosing regimens. Further well-designed, comparative studies are needed to determine the role of daptomycin TDM in patients with Gram-positive infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Iain J. Abbott, Elke van Gorp, Hugh Cottingham, Nenad Macesic, Steven C. Wallis, Jason A. Roberts, Joseph Meletiadis, Anton Y. Peleg
Summary: The study found that high-dose oral ciprofloxacin therapy (750 mg 12 hourly) has good antibacterial activity against ceftriaxone-resistant Escherichia coli, especially with ciprofloxacin MIC <= 1 mg/L.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Infectious Diseases
Theresa Maria Wagner, Benjamin Peter Howden, Arnfinn Sundsfjord, Kristin Hegstad
Summary: The acquisition and expression of antimicrobial resistance (AMR) mechanisms in bacteria are often associated with a fitness cost. Transiently silent acquired AMR (tsaAMR) refers to acquired antimicrobial resistance genes with a corresponding phenotype within the wild-type distribution or below the clinical breakpoint for susceptibility, for which genetic alterations can mediate expression to a clinically relevant level of resistance. The phenomenon of tsaAMR is likely to increase due to the overall expansion of acquired AMR in bacterial pathogens and the use of genotypic methods in combination with conventional phenotypic antimicrobial susceptibility testing (AST).
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Microbiology
Benjamin P. Howden, Stefano G. Giulieri, Tania Wong Fok Lung, Sarah L. Baines, Liam K. Sharkey, Jean Y. H. Lee, Abderrahman Hachani, Ian R. Monk, Timothy P. Stinear
Summary: Invasive Staphylococcus aureus infections are common and often result in high mortality due to drug resistance. This review examines recent advances in understanding the interactions between S. aureus and its host, including immune responses, metabolism, and genomic plasticity. The authors also discuss the challenges in vaccine development and the role of other bacteria in shaping S. aureus colonization.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Virology
Ashleigh F. Porter, Damian F. J. Purcell, Benjamin P. Howden, Sebastian Duchene
Summary: The study investigates the genetic adaptations of SARS-CoV-2 in mink hosts. The evolutionary rate of the virus increased upon introduction into minks before returning to the normal range in humans. The study also identified specific mutations in mink-associated lineages, highlighting the importance of ongoing surveillance of zoonotic infections.
Article
Microbiology
Jacqueline M. M. Morris, Karolina Mercoulia, Mary Valcanis, Claire L. L. Gorrie, Norelle L. L. Sherry, Benjamin P. P. Howden
Summary: Our study demonstrates that Vibrio alginolyticus isolated from cooked prawn is capable of harboring antimicrobial resistance genes of public health concern, specifically a chromosomally located bla(NDM-1) gene, and there is the potential for transmission of resistance genes.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Micaela Mossop, Luca Robinson, Jhih-Hang Jiang, Anton Y. Peleg, Luke Blakeway, Nenad Macesic, Audrey Perry, Stephen Bourke, Fatima R. Ulhuq, Tracy Palmer
Summary: One third of CF patients in the UK are co-infected with both Staphylococcus aureus and Pseudomonas aeruginosa, which contribute to lung tissue destruction and respiratory failure. This study aims to characterize twenty-five clinical S. aureus isolates from CF patients, including those with mono- and coinfection with P. aeruginosa, using molecular and phenotypic tools.
JOURNAL OF MEDICAL MICROBIOLOGY
(2023)
Article
Pathology
Xenia Kostoulias, Christina C. Chang, Jessica Wisniewski, Iain J. Abbott, Helen Zisis, Amanda Dennison, Denis W. Spelman, Anton Y. Peleg
Summary: We investigated the effectiveness of ceftolozane-tazobactam (C/T) in a high-risk population for antimicrobial resistance, specifically patients with cystic fibrosis (CF) and lung transplantation (LTx). Out of 163 clinical Pseudomonas aeruginosa isolates collected from a tertiary hospital in Melbourne, Australia, 81.6% were susceptible to C/T. Among the multidrug resistant (MDR) and extensively drug resistant (XDR) isolates, C/T showed susceptibility in 88.3% and 28.1% of cases, respectively. In conclusion, C/T maintained its activity against a significant portion of MDR and XDR P. aeruginosa isolates from CF and post-LTx patients.
Article
Microbiology
Yao Sun, Xenia Kostoulias, Yue Qu
Summary: Recurrent vulvovaginal candidiasis (RVVC) is a difficult-to-treat Candida infection that affects the morbidity of many otherwise healthy women. Biofilm formation of Candida has been identified as an important factor in the pathogenesis and treatment failure of RVVC. This review discusses the roles of Candida biofilms in RVVC.
MICROBIOLOGY AUSTRALIA
(2023)
Article
Multidisciplinary Sciences
Jessica E. Stockdale, Kurnia Susvitasari, Paul Tupper, Benjamin Sobkowiak, Nicola Mulberry, Anders Goncalves da Silva, Anne E. Watt, Norelle L. Sherry, Corinna Minko, Benjamin P. Howden, Courtney R. Lane, Caroline Colijn
Summary: This article introduces a method for estimating serial intervals using virus sequences and applies it to case clusters of SARS-CoV-2 in Victoria, Australia.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Charlie Higgs, Lamali Sadeesh Kumar, Kerrie Stevens, Janet Strachan, Norelle L. Sherry, Kristy Horan, Josh Zhang, Timothy P. Stinear, Benjamin P. Howden, Claire L. Gorrie
Summary: Streptococcus pneumoniae, a major human pathogen, has undergone significant changes in its epidemiology and distribution in Australia following the introduction of pneumococcal conjugate vaccines. This study used whole-genome sequencing and antimicrobial susceptibility data to examine the population structure and prevalence of antimicrobial resistance in Victoria, Australia. The results showed high diversity among isolates, with multiple serotypes and sequence types identified. Antimicrobial resistance, particularly to penicillin, was also observed. High-risk sub-populations with specific serotypes were identified. The study provides insights for IPD surveillance and prevention strategies.
MICROBIAL GENOMICS
(2023)
Article
Infectious Diseases
Jipan Yi, Yao Sun, Chenghong Zeng, Xenia Kostoulias, Yue Qu
Summary: Biofilm formation is crucial for fungal pathogens to cause keratitis in patients wearing contact lenses. However, current contact lens care systems and solutions do not specifically target fungal biofilms. This review aims to explore the link between fungal biofilms and contact lens-associated fungal keratitis, and enhance our understanding of its importance in infection pathogenesis and persistence.
Article
Microbiology
Charles Nunez, Xenia Kostoulias, Anton Peleg, Francesca Short, Yue Qu
Summary: This study compares the contributory roles of biofilm formation and capsule production in bacterial survival on hospital surfaces. The results show that biofilm formation plays a crucial role in bacterial survival, while encapsulation plays a minor role and may even negatively impact bacterial biofilm formation and hospital survival.
Review
Microbiology
Jhih-Hang Jiang, David R. Cameron, Cara Nethercott, Marta Aires-de-Sousa, Anton Y. Peleg
Summary: This review focuses on the mechanisms that trigger the establishment and maintenance of current, dominant MRSA lineages across the globe. Factors that influence MRSA's ability to colonize and cause disease within a host are discussed, with an emphasis on colonization and niche adaptation. Understanding these mechanisms may lead to the development of targeted therapies.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
