Article
Nanoscience & Nanotechnology
Henry Devlin, Stephanie Fulaz, Dishon Wayne Hiebner, James P. O'Gara, Eoin Casey
Summary: The study demonstrates that enzyme-functionalized mesoporous silica nanoparticles can significantly enhance the efficacy of three enzymes against Staphylococcus aureus cells and biofilms. The combined use of these enzymes further improves treatment efficacy, particularly for methicillin-resistant Staphylococcus aureus infections, showing potential for clinical applications.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Microbiology
Shu Chen, Pingping Zhang, Liyin Xiao, Ying Liu, Kuihai Wu, Guoying Ni, Hejie Li, Tianfang Wang, Xiaolian Wu, Guoqiang Chen, Xiaosong Liu
Summary: The study shows that two peptides isolated from an Australian frog, caerin 1.1 and 1.9, exhibit high bioactivity against various bacteria strains and can inhibit the growth of antibiotic-resistant bacteria in mice without inducing resistance.
MICROBIOLOGY SPECTRUM
(2021)
Article
Chemistry, Medicinal
Sandeep Lohan, Anastasia G. Konshina, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang
Summary: A series of short helical cationic peptides were designed and synthesized to have broad-range bactericidal activity and selectivity toward bacterial cells. The lead peptide 8b showed broad-spectrum activity against both Gram-positive and Gram-negative bacteria, as well as selectivity towards prokaryotic cells. The peptide's rapid membranolytic action was confirmed through assays and microscopy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Immunology
Jingyan Guan, Congxiao Wu, Yunfan He, Feng Lu
Summary: The skin acts as a critical barrier tissue against external pathogens, with its uppermost epidermal layer and skin barrier immunity playing a vital role in maintaining its barrier function. The integrity and effectiveness of skin barrier immunity depend on the close interaction and communication between immune cells and the skin environment. Skin-associated adipocytes have been found to modulate skin immune responses and infection through the secretion of cytokines, adipokines, and antimicrobial peptides. This review summarizes recent research on the interactions between skin-associated adipocytes and other skin cells in maintaining the integrity and effectiveness of skin barrier immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Aneta Zegar, Urszula Godlewska, Dorota Kozlowska-Chmielewska, Pawel Majewski, Brian A. Zabel, Joanna Cichy
Summary: Chemerin-derived peptide p4 can restrict the growth of methicillin-resistant Staphylococcus aureus (MRSA) and collaborates additively with LL-37 in inhibiting the growth of S. aureus, including MRSA. It has been shown to be effective in reducing MRSA burden in vivo and levels of skin-infiltrating leukocytes in S. aureus-infected AD-like skin.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Chenghua Song, Ruichao Wen, Jiaxuan Zhou, Xiaoyan Zeng, Zi Kou, Jia Zhang, Tao Wang, Pengkang Chang, Yi Lv, Rongqian Wu
Summary: The antimicrobial activity and mechanism of a novel synthetic peptide GK-19, derived from scorpion venom-derived peptide AamAP1, were evaluated. GK-19 showed inhibitory effects on bacterial growth and fungi by disrupting the microbial cell membrane. It exhibited low toxicity to mammalian cells, low hemolytic activity, high stability in plasma, and significant antimicrobial and healing effects in mice models of skin and soft tissue infections.
Article
Dermatology
Bernadetta Bilska, Aneta Zegar, Andrzej T. Slominski, Konrad Kleszczynski, Joanna Cichy, Elzbieta Pyza
Summary: The gene expression of Rarres2, Camp, and Defb1 in mouse skin was highest during high activity periods, but this rhythm was masked under constant darkness, while the gene expression of Defb3 and Defb14 showed the highest levels during sleep and were maintained under constant darkness. This indicates a correlation between specific antimicrobial peptides and different physiological states, with some being influenced by light-dark cycles and others being regulated by a circadian clock.
EXPERIMENTAL DERMATOLOGY
(2021)
Article
Microbiology
Henk Scheper, Julia M. Wubbolts, Joanne A. M. Verhagen, Adriette W. de Visser, Robert J. P. van der Wal, Leo G. Visser, Mark G. J. de Boer, Peter H. Nibbering
Summary: Prosthetic joint infection is a severe complication of arthroplasty, often caused by biofilm formation. Current treatment strategies are often ineffective, prompting the need for innovative anti-biofilm and anti-persister agents. A study developed an in vitro model for PJI using various surfaces exposed to antibiotics, with SAAP-148 showing high effectiveness against persister bacteria.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xiuhui Lin, Jian He, Wanlin Li, Yuchen Qi, Huiqun Hu, Dongxiao Zhang, Feng Xu, Xiaoyuan Chen, Min Zhou
Summary: The encapsulated lysostaphin microspheres (LyIR@MS) effectively treat MRSA-induced pneumonia by improving biofilm sensitivity to host neutrophils, enhancing survival rate, and reducing inflammatory injury.
Review
Infectious Diseases
Mohammad Asyraf Adhwa Masimen, Noor Aniza Harun, M. Maulidiani, Wan Iryani Wan Ismail
Summary: Antibiotics are a medical miracle, but bacteria quickly develop resistance, leading to MRSA becoming one of the most prominent antibiotic-resistant bacteria. Antimicrobial peptides and silver nanoparticles are considered alternative treatments for MRSA due to their broad-spectrum properties and potential synergistic effects.
Article
Chemistry, Medicinal
Jinwei Chai, Jiena Wu, Jinqiao Li, Hang Liao, Wancheng Lu, Ruiyin Guo, Zuoyan Shao, Mohamed Amine Jmel, Larissa Almeida Martins, Tilman Hackeng, Hans Ippel, Ingrid Dijkgraaf, Michail Kotsyfakis, Xueqing Xu
Summary: A novel Ranacyclin peptide called Ranacin was identified from the skin of Pelophylax nigromaculatus frog. Ranacin effectively inhibited trypsin and exhibited anticoagulant and antioxidant activities in vitro. Treatment with Ranacin significantly alleviated the severity of pancreatitis in L-Arg-induced AP mice. Structure-activity studies suggested that sequences outside the trypsin inhibitory loop (TIL) of Ranacin may play an important role in its efficacy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Brittany Woodby, Erika Pambianchi, Francesca Ferrara, Jean-Philippe Therrien, Alessandra Pecorelli, Nicolo' Messano, Mary Ann Lila, Giuseppe Valacchi
Summary: Exposure to O3 is reported to affect AMP levels in the skin, playing a role in skin inflammatory conditions, indicating a possible defensive strategy against pollution-associated skin conditions.
Review
Microbiology
Luisa Zupin, Carlos Andre Dos Santos-Silva, Aya R. Hamad Al Mughrbi, Livia Maria Batista Vilela, Ana Maria Benko-Iseppon, Sergio Crovella
Summary: Zoonoses have gained significant attention due to the emergence of new human pathogens, most of which can be classified as zoonotic infections. Efforts are needed to understand the spread and pathogenicity of zoonoses, as well as develop clinical interventions and antimicrobial drugs. Antimicrobial peptides show promise in combating infectious diseases, but further studies are required to understand their mechanism and evaluate their clinical application in humans.
Article
Engineering, Biomedical
Hui Shao, Jin Zhou, Xiaoqian Lin, Yue Zhou, Yumeng Xue, Weili Hong, Xubo Lin, Xiaoling Jia, Yubo Fan
Summary: Developing new antimicrobial agents to combat drug-resistant pathogens and biofilms is an urgent task. Cationic antimicrobial peptides (AMPs) have potential due to their unique membrane rupture mechanism, but their high toxicity and low stability limit their application. In this study, a biomimetic strategy was used to construct cationic peptide-conjugated liposomes, inspired by cell-penetrating peptides (CPPs), to enhance antibacterial efficacy and biosafety. Computational simulation and experimental investigations identified the optimal peptide-conjugated liposomes, which showed enhanced antibacterial efficacy without compromising cytotoxicity. This bio-inspired design could contribute to the development of next-generation antimicrobials.
Review
Microbiology
Mi Nguyen-Tra Le, Miki Kawada-Matsuo, Hitoshi Komatsuzawa
Summary: Antimicrobial peptides (AMPs) are potential therapeutic drugs against multidrug-resistant bacteria due to their high efficacy and the poor ability of microorganisms to develop resistance to them.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Nader S. Abutaleb, Ahmed Elkashif, Daniel P. Flaherty, Mohamed N. Seleem
Summary: Acetazolamide showed promising inhibitory effects against enterococci and outperformed linezolid in VRE mouse models, suggesting it as a potential treatment option for VRE infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Nader S. Abutaleb, Ahmed E. M. Elhassanny, Alessio Nocentini, Chad S. Hewitt, Ahmed Elkashif, Bruce R. Cooper, Claudiu T. Supuran, Mohamed N. Seleem, Daniel P. Flaherty
Summary: Ethoxzolamide exhibits potent anti-gonococcal activity and warrants further investigation as an effective agent against Neisseria gonorrhoeae.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mohamed A. Seleem, Nicholas A. Wood, Amanda J. Brinkworth, Srikanth Manam, Rey A. Carabeo, Ashlesh K. Murthy, Scot P. Ouellette, Martin Conda-Sheridan
Summary: This research identified compounds with enhanced anti-chlamydial potency, which were not harmful to mammalian cells and did not affect other common bacterial strains. Molecule 20 showed the highest activity, and in combination with the antibiotic azithromycin, acted synergistically to inhibit chlamydial growth.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
George A. Naclerio, Nader S. Abutaleb, Kenneth Onyedibe, Caroline Karanja, Hassan E. Eldesouky, Hsin-Wen Liang, Alexandra Dieterly, Uma K. Aryal, Tiffany Lyle, Mohamed N. Seleem, Herman O. Sintim
Summary: This study elucidates the mechanism by which HSGN-94 inhibits LTA biosynthesis and demonstrates its efficacy in reducing MRSA load and pro-inflammatory cytokines in a mouse model. HSGN-94 shows promise as a potential drug for staphylococcal infections.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ahmed E. M. Elhassanny, Nader S. Abutaleb, Mohamed N. Seleem
Summary: This study demonstrated the in vivo activity of auranofin against Neisseria gonorrhoeae, proving its potential as a promising antimicrobial agent.
Article
Biochemistry & Molecular Biology
Weiwei An, Katrina J. Holly, Alessio Nocentini, Ryan D. Imhoff, Chad. S. Hewitt, Nader S. Abutaleb, Xufeng Cao, Mohamed N. Seleem, Claudiu T. Supuran, Daniel P. Flaherty
Summary: This paper discusses the inhibition mechanism and effects of the inhibitor acetazolamide (AZM) and its analogs against vancomycin-resistant enterococci (VRE), as well as the research methods related to binding to different enzymes and selectivity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Rusha Pal, Mohamed N. Seleem
Summary: This study reports a novel natural product scaffold as a potential therapeutic choice for C. difficile infection. Six compounds with potent activity against C. difficile were identified and found to be non-toxic to human cells. These compounds also inhibited the production of key toxins and exhibited superior bactericidal activity compared to standard treatment. In a mouse model, one compound showed 100% protection against clinical manifestations of the disease.
Article
Chemistry, Medicinal
Luana Janaina de Campos, Mohamed A. . Seleem, Jiachen Feng, Kelly Mari Pires de Oliveira, Joao Victor de Andrade dos Santos, Shivdeep Hayer, Jonathan B. Clayton, Sharvath Kathi, Derek J. Fisher, Scot P. Ouellette, Martin Conda-Sheridan
Summary: Chlamydia trachomatis (CT) is the main cause of sexually transmitted bacterial disease in the United States. The lack of drug selectivity poses a challenge for current antichlamydial pharmacotherapy. By studying the disruption of CT-ClpXP by dihydrothiazepines, we synthesized a library of these compounds and evaluated their antichlamydial activity. We also demonstrated the inhibitory effect of our lead compound on ClpX ATPase activity and its promising selectivity, cytotoxicity, mutagenic potential, and in vitro stability. We generated a 2D QSAR model to aid in the identification of more potent antichlamydial molecules. This study suggests that dihydrothiazepines are a promising starting point for the development of selective antichlamydial drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Anil Kumar Marapaka, Alessio Nocentini, Molly S. Youse, Weiwei An, Katrina J. Holly, Chittaranjan Das, Ravi Yadav, Mohamed N. Seleem, Claudiu T. Supuran, Daniel P. Flaherty
Summary: Drug-resistant Neisseria gonorrhoeae poses a serious threat to public health. The research team solved the structure of carbonic anhydrase inhibitors bound to the essential alpha-carbonic anhydrase isoform from N. gonorrhoeae, revealing differences compared to the human enzyme.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Microbiology
Yehia Elgammal, Ehab A. Salama, Mohamed N. Seleem
Summary: We have identified atazanavir as a potent drug that can resensitize clinical isolates of C. auris to azole antifungal drugs. Atazanavir is capable of inhibiting efflux pumps, glucose transport, and ATP synthesis in all tested isolates of C. auris. Furthermore, the combination of itraconazole with atazanavir-ritonavir significantly reduces the burden of azole-resistant C. auris in murine kidneys.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Nader S. Abutaleb, Annadka Shrinidhi, Aloka B. Bandara, Mohamed N. Seleem, Daniel P. Flaherty
Summary: Vancomycin-resistant enterococci (VRE) are drug-resistant pathogens that require new therapeutic approaches. Decolonization of VRE from carriers can reduce the risk of infections in healthcare settings. This study found that carbonic anhydrase inhibitors showed better efficacy in VRE gut decolonization compared to linezolid.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Materials Science, Biomaterials
Alexander Roth, Akshay Krishnakumar, Robyn R. R. McCain, Murali Kanaan Maruthamuthu, MacKenzie McIntosh, Yue Xiang Chen, Abigail D. D. Cox, Amber S. S. Jannasch, Juliane Nguyen, Mohamed N. N. Seleem, Rahim Rahimi
Summary: Recent studies have demonstrated that combining gaseous ozone and antibiotics through portable systems is a promising approach to eradicating antibiotic-resistant Gram-negative bacteria in wound infections. An optimized combination delivery of 4 mg/h of ozone and 200 μg/cm2 of topical antibiotics was found to effectively eliminate bacteria in just 6 hours, with minimal cytotoxicity to human fibroblast cells. Furthermore, in vivo studies on pig models showed no signs of adverse effects even after 5 days of continuous administration.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Infectious Diseases
Ehab A. Salama, Hassan E. Eldesouky, Yehia Elgammal, Nader S. Abutaleb, Mohamed N. Seleem
Summary: This study found that the HIV protease inhibitors lopinavir and ritonavir, when used in combination with azole antifungals, can effectively treat Candida auris infections that have developed resistance to antifungal drugs. The study demonstrated the synergistic interactions between lopinavir, ritonavir, and azole antifungals, and the potential of ritonavir to interfere with fungal efflux pumps. In a mouse model, ritonavir enhanced the activity of lopinavir and significantly reduced the fungal burden in the kidneys.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Immunology
Babatomiwa Kikiowo, Aloka B. Bandara, Nader S. Abutaleb, Mohamed N. Seleem
Summary: Gonococcal resistance to antibiotics is increasing, necessitating the development of novel drugs. In this study, streptomycin-resistant mutants of azithromycin and ceftriaxone-resistant Neisseria gonorrhoeae were constructed and their colonization efficacy in mouse models was determined, providing a basis for evaluating the effectiveness of new agents.
PATHOGENS AND DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Hanzada T. Nour T. El-Din, Mohamed M. Elsebaie, Nader S. Abutaleb, Ahmed M. M. Kotb, Ahmed S. Attia, Mohamed N. Seleem, Abdelrahman S. Mayhoub
Summary: In this study, a series of structurally related acetylenic-diphenylurea derivatives carrying the aminoguanidine moiety were tested for their antibacterial efficacy against multidrug-resistant Gram-positive clinical isolates. Compound 18 showed superior bacteriological characteristics compared to the lead compound I. In addition, compound 18 demonstrated excellent in vitro antibacterial profile, high tolerability towards mammalian cells, and significant effectiveness in controlling MRSA infection in an animal model.
RSC MEDICINAL CHEMISTRY
(2023)
