Akash Dutta, Peehu Sharma, Dharam Dass, Venkateswarlu Yarlagadda
The prevalence of antimicrobial resistance in Gram-negative bacteria poses a greater challenge due to their intrinsic resistance to many antibiotics. Recently, darobactins have emerged as a novel class of antibiotics originating from previously unexplored Gram-negative bacterial species such as Photorhabdus , Vibrio , Pseudoalteromonas and Yersinia . Darobactins belong to the ribosomally synthesized and post-translationally modified peptide (RiPP) class of antibiotics, exhibiting selective activity against Gram-negative bacteria...
July 19, 2024: ACS Infectious Diseases
Ashim Kumar Dubey, Deepika Sardana, Taru Verma, Parvez Alam, Avik Chattopadhyay, Santhi Sanil Nandini, Balaram Khamari, Eswarappa Pradeep Bulagonda, Sobhan Sen, Dipankar Nandi
Accurate detection of bacterial antibiotic sensitivity is crucial for theranostics and the containment of antibiotic-resistant infections. However, the intricate task of detecting and quantifying the antibiotic-induced changes in the bacterial cytoplasmic membrane, and their correlation with other metabolic pathways leading to antibiotic resistance, poses significant challenges. Using a novel class of 4-aminophthalimide (4AP)-based fluorescent dyes with precisely tailored alkyl chains, namely 4AP-C9 and 4AP-C13, we quantify stress-mediated alterations in E...
July 18, 2024: ACS Infectious Diseases
Titilade Kehinde Ayandeyi Teibo, Rubia Laine de Paula Andrade, Rander Junior Rosa, Paula Daniella de Abreu, Oluwaseyi Ademo Olayemi, Yan Mathias Alves, Reginaldo Bazon Vaz Tavares, Fernanda Bruzadelli Paulino da Costa, Heriederson Sávio Dias Moura, Letícia Perticarrara Ferezin, Ariela Fehr Tártaro, Mônica Chiodi Toscano de Campos, Natacha Martins Ribeiro, Thaís Zamboni Berra, Ricardo Alexandre Arcêncio
This study evaluated the barriers that interfere with access to diagnosis and treatment of tuberculosis (TB) from the perspective of the patient and health professionals globally. Using the PICo acronym, the question we asked was "What are the barriers that interfere with access to tuberculosis diagnosis and treatment (I) from the perspective of patients and/or health professionals (P) across countries globally (Co)?". We searched the following databases: EMBASE, Scopus, MEDLINE, Latin American and Caribbean Literature in Health Sciences (LILACS), and Web of Science...
July 18, 2024: ACS Infectious Diseases
Edubiel A Alpizar-Sosa, Flavia M Zimbres, Brian S Mantilla, Emily A Dickie, Wenbin Wei, Gabriela A Burle-Caldas, Laura N S Filipe, Katrien Van Bocxlaer, Helen P Price, Ana V Ibarra-Meneses, Francis Beaudry, Christopher Fernandez-Prada, Philip D Whitfield, Michael P Barrett, Paul W Denny
The lack of effective vaccines and the development of resistance to the current treatments highlight the urgent need for new anti-leishmanials. Sphingolipid metabolism has been proposed as a promising source of Leishmania -specific targets as these lipids are key structural components of the eukaryotic plasma membrane and are involved in distinct cellular events. Inositol phosphorylceramide (IPC) is the primary sphingolipid in the Leishmania species and is the product of a reaction mediated by IPC synthase (IPCS)...
July 18, 2024: ACS Infectious Diseases
Mark S Butler, Waldemar Vollmer, Emily C A Goodall, Robert J Capon, Ian R Henderson, Mark A T Blaskovich
There is a lack of new antibiotics to combat drug-resistant bacterial infections that increasingly threaten global health. The current pipeline of clinical-stage antimicrobials is primarily populated by "new and improved" versions of existing antibiotic classes, supplemented by several novel chemical scaffolds that act on traditional targets. The lack of fresh chemotypes acting on previously unexploited targets (the "holy grail" for new antimicrobials due to their scarcity) is particularly unfortunate as these offer the greatest opportunity for innovative breakthroughs to overcome existing resistance...
July 17, 2024: ACS Infectious Diseases
Paige R Gruenke, Miles D Mayer, Rachna Aneja, William J Schulze, Zhenwei Song, Donald H Burke, Xiao Heng, Margaret J Lange
The HIV-1 capsid protein (CA) assumes distinct structural forms during replication, each presenting unique, solvent-accessible surfaces that facilitate multifaceted functions and host factor interactions. However, functional contributions of individual CA structures remain unclear, as evaluation of CA presents several technical challenges. To address this knowledge gap, we identified CA-targeting aptamers with different structural specificities, which emerged through a branched SELEX approach using an aptamer library previously selected to bind the CA hexamer lattice...
July 17, 2024: ACS Infectious Diseases
Asma Akter, George Firth, Afnan M F Darwesh, Margaret S Cooper, Hataichanok Chuljerm, Agostino Cilibrizzi, Philip J Blower, Robert C Hider, Oliver Lyons, Silke Schelenz, Varun Mehra, Vincenzo Abbate
Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([68 Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation...
July 16, 2024: ACS Infectious Diseases
Isabela A A Bessa, Dayenny L D'Amato, Ana Beatriz C Souza, Daniel P Levita, Camille C Mello, Aline F M da Silva, Thiago C Dos Santos, Célia M Ronconi
Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts...
July 13, 2024: ACS Infectious Diseases
Hao Wu, Zhe Ji, Xin Huang, Liping Li, Sijin Hang, Jinhua Yu, Hui Lu, Yuanying Jiang
Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo...
July 12, 2024: ACS Infectious Diseases
Damilohun Samuel Metibemu, Olawale Samuel Adeyinka, John Falode, Olamide Crown, Ifedayo Victor Ogungbe
The Alphavirus genus includes viruses that cause encephalitis due to neuroinvasion and viruses that cause arthritis due to acute and chronic inflammation. There is no approved therapeutic for alphavirus infections, but significant efforts are ongoing, more so in recent years, to develop vaccines and therapeutics for alphavirus infections. This review article highlights some of the major advances made so far to identify small molecules that can selectively target the structural and the nonstructural proteins in alphaviruses with the expectation that persistent investigation of an increasingly expanding chemical space through a variety of structure-based design and high-throughput screening strategies will yield candidate drugs for clinical studies...
July 11, 2024: ACS Infectious Diseases
Ning Gao, Xiaoyan Ju, Xiting Jiao, Yuanyuan Qi, Ye Tian, Shidong Jiang, Zhongwei Niu, Shaozhen Zhao, Ruibo Yang
Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK13 peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma...
July 11, 2024: ACS Infectious Diseases
Mohammad Sadik Ali, Hima Sree Buddhiraju, Mounika Gubige, Apoorva Basa, Gnaneshwar Gupta K, Bantal Veeresh, Aravind Kumar Rengan
Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site...
July 11, 2024: ACS Infectious Diseases
F Ifthiha Mohideen, Lara K Mahal
Glycans play critical roles in the host-pathogen interactions leading to infection. However, we still understand very little about the dynamic nature of glycosylation in response to infection and its function in modulating host immunity. Many of the host proteins involved in immune defense are glycoproteins. Furthermore, the innate immune system recognizes glycans. The glycoform of a protein can impact proteolytic stability, receptor interactions, serum half-life, and other aspects. New, cutting-edge chemical biology tools are shedding light on the interplay between infection and the host glycome...
July 11, 2024: ACS Infectious Diseases
Wen Chao, Lijuan Qiu, Lu Gao, Jia Feng, Yu Liu, Lan Yan, Yuanying Jiang, Quanzhen Lv
The development of new effective antifungal agents is essential to combat fungal infections. Tetrahydrocarbazole has been exploited as a promising skeleton against various pathogenic microorganisms and is used to search for novel active antifungal compounds. In this study, a library composed of small tetrahydrocarbazole compounds was screened, and a potent antifungal agent, CAR-8, was identified with a minimum inhibitory concentration of 2-4 μg/mL against Candida albicans . CAR-8 showed strong fungicidal activities and killed almost all C...
July 11, 2024: ACS Infectious Diseases
Sucharita Bhowmick, Subhadeep Gupta, Samiran Mondal, Amirul Islam Mallick
Low-pathogenic avian influenza virus (LPAIV) remains the most common subtype of type-A influenza virus that causes moderate to severe infection in poultry with significant zoonotic and pandemic potential. Due to high mutability, increasing drug resistance, and limited vaccine availability, the conventional means to prevent intra- or interspecies transmission of AIV is highly challenging. As an alternative to control AIV infections, cytokine-based approaches to augment antiviral host defense have gained significant attention...
July 6, 2024: ACS Infectious Diseases
Akanksha, Sarika Mehra
Antibiotic resistance is a pressing health issue, with the emergence of resistance in bacteria outcompeting the discovery of novel drug candidates. While many studies have used Adaptive Laboratory Evolution (ALE) to understand the determinants of resistance, the influence of the drug dosing profile on the evolutionary trajectory remains understudied. In this study, we employed ALE on Mycobacterium smegmatis exposed to various concentrations of Norfloxacin using both cyclic constant and stepwise increasing drug dosages to examine their impact on the resistance mechanisms selected...
July 3, 2024: ACS Infectious Diseases
Valeria Francesconi, Marco Rizzo, Cecilia Pozzi, Lorenzo Tagliazucchi, Claude U Konchie Simo, Giulia Saporito, Giacomo Landi, Stefano Mangani, Anna Carbone, Silvia Schenone, Nuno Santarém, Joana Tavares, Anabela Cordeiro-da-Silva, Maria Paola Costi, Michele Tonelli
Folate enzymes, namely, dihydrofolate reductase (DHFR) and pteridine reductase (PTR1) are acknowledged targets for the development of antiparasitic agents against Trypanosomiasis and Leishmaniasis. Based on the amino dihydrotriazine motif of the drug Cycloguanil (Cyc), a known inhibitor of both folate enzymes, we have identified two novel series of inhibitors, the 2-amino triazino benzimidazoles ( 1 ) and 2-guanidino benzimidazoles ( 2 ), as their open ring analogues. Enzymatic screening was carried out against PTR1, DHFR, and thymidylate synthase (TS)...
July 2, 2024: ACS Infectious Diseases
Charmante Registre, Luciana Miranda Silva, Farah Registre, Rodrigo Dian de Oliveira Aguiar Soares, Karina Taciana Santos Rubio, Simone Pinto Carneiro, Orlando David Henrique Dos Santos
Millions of people worldwide are affected by leishmaniasis, caused by the Leishmania parasite. Effective treatment is challenging due to the biological complexity of the parasite, drug toxicity, and increasing resistance to conventional drugs. To combat this disease, the development of specific strategies to target and selectively eliminate the parasite is crucial. This Review highlights the importance of amino acids in the developmental stages of Leishmania as a factor determining whether the infection progresses or is suppressed...
July 1, 2024: ACS Infectious Diseases
Tingting Guo, Liying Yang, Na Zhou, Zichen Wang, Changchao Huan, Jun Zhou, Tao Lin, Guangyu Bao, Jian Hu, Guocai Li
Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased...
July 1, 2024: ACS Infectious Diseases
Napon Nilchan, Romchat Kraivong, Prasit Luangaram, Anunyaporn Phungsom, Mongkhonphan Tantiwatcharakunthon, Somchoke Traewachiwiphak, Tanapan Prommool, Nuntaya Punyadee, Panisadee Avirutnan, Thaneeya Duangchinda, Prida Malasit, Chunya Puttikhunt
The envelope protein of dengue virus (DENV) is a primary target of the humoral immune response. The domain III of the DENV envelope protein (EDIII) is known to be the target of multiple potently neutralizing antibodies. One such antibody is 3H5, a mouse antibody that binds strongly to EDIII and potently neutralizes DENV serotype 2 (DENV-2) with unusually minimal antibody-dependent enhancement (ADE). To selectively display the binding epitope of 3H5, we strategically modified DENV-2 EDIII by shielding other known epitopes with engineered N-glycosylation sites...
June 29, 2024: ACS Infectious Diseases
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