Antimicrobial Agents and Chemotherapy

The type VI secretion system (T6SS) is a widespread bacterial nanomachine involved in interbacterial competition and environmental adaptation. Its distribution and evolutionary significance in Acinetobacter baumannii is not fully understood. Here, we investigated the ST19 lineage, revealing a near-complete absence of the T6SS across 159 genomes from diverse geographic and clinical origins. Comparative genomic analysis showed that the T6SS locus in ST19 is frequently disrupted, with some isolates...

Malaria remains a persistent global health challenge, and emerging resistance to artemisinin-based therapy threatens disease control. Here, we report the evaluation of scaffolds selected from three classes of indole hybrids. A library of 24 synthetically designed indoles was screened in vitro against Plasmodium falciparum sexual and asexual forms. The derivatives displayed a wide range of activity, from inactive to potent, with compound ARN53 exhibiting the strongest inhibition (IC₅₀ = 684.8 ±...

Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam are key therapeutic options for infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Resistance may emerge during therapy, but knowledge on mutant prevention and collateral effects remains limited. Killing kinetics assays of ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and the combination of ceftazidime-avibactam with meropenem (CZA + MER) were performed against clinical KPC-3-ST307-Kp...

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children worldwide. Safe and effective treatments for RSV remain limited. In this investigation, we screened more than 100 anti-influenza compounds from a small-molecule library using an A549 cell model. Among these drugs, lapatinib emerged as a promising candidate and demonstrated potent anti-RSV activity along with low cytotoxicity. Lapatinib not only significantly suppressed...

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a critical global health threat. CRAB is designated a WHO Priority 1st pathogen due to high mortality and limited therapeutic options. Meropenem, a first-line carbapenem, exhibits dose-dependent nephrotoxicity, hepatotoxicity, and neurotoxicity-especially in critically ill patients-necessitating strategies to reduce dosing while maintaining efficacy. Class D β-lactamase OXA23 is the predominant driver of carbapenem resistance, which is...

Putative novel β-lactamase-encoding genes are increasingly identified in whole-genome sequencing (WGS) data, often without phenotypic or biochemical characterization. Here, we characterized the chromosome-encoded GUA-1 Ambler class A β-lactamase from the clinical isolate Pseudomonas guariconensis-like 65411. Among the 40 P. guariconensis genomes available in the GenBank database, only 8 carried a bla(GUA-like) gene, whereas the others encoded an AmpC β-lactamase, suggesting the existence of two...

Staphylococcus aureus remains a major public health concern due to its capacity for colonization, transmission, and antimicrobial resistance. Both methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) serve as reservoirs for resistance determinants, including those conferring reduced susceptibility to topical decolonization agents. We analyzed 2,330 S. aureus isolates collected between 2022 and 2025 from hospitals and community clinics in New Jersey and New York City,...

No abstract

Feline infectious peritonitis (FIP), a fatal disease caused by FIP virus (FIPV), currently lacks effective vaccines and treatments. Imipramine, a tricyclic antidepressant with known broad-spectrum antiviral properties, was investigated for its efficacy against FIPV. Our in vitro studies demonstrated that imipramine inhibits FIPV infection in a dose-dependent manner, with a high selectivity index (SI = 291) and maximal effect when administered during co-treatment. Time-of-addition assays revealed...

Large-scale genomic studies have advanced our understanding of the global dissemination of antimicrobial-resistant (AMR) bacteria, yet most have been limited by inconsistent sampling periods, heterogeneous geographic coverage, and weak epidemiological linkages among isolates. Consequently, the fine-scale processes underlying the establishment and maintenance of AMR pandemics remain unclear. To address these limitations, we established a rigorously controlled community- and household-integrated...

Antimicrobial efficacy in pneumonia is strongly influenced by site-specific drug exposure; however, pharmacokinetic/pharmacodynamic (PK/PD) indices based on plasma concentrations may not adequately reflect drug exposure at the pulmonary infection site. This study evaluated how differences in pulmonary distribution influence the magnitude and interpretation of PK/PD targets by comparing three fluoroquinolones with distinct epithelial lining fluid (ELF) penetration profiles. Using a murine...

Toxoplasmosis, caused by the protozoan Toxoplasma gondii, affects nearly one-third of the global population and may result in severe congenital, ocular, and neurological manifestations. Current therapies are limited by toxicity, poor efficacy against chronic infection, and lack of activity against tissue cysts, highlighting the need for new therapeutic strategies. Aspartic proteases represent promising but underexplored drug targets in T. gondii. In this study, we evaluated the anti-T. gondii...

Candida biofilms produce an extracellular matrix that sequesters antifungals, allowing cells to proliferate despite otherwise therapeutic concentrations. A prior study found turbinmicin to inhibit the release of the extracellular vesicles (EVs) required for matrix delivery and drug resistance. Here, we show that turbinmicin also alters the cargo loaded into EVs, decreasing the relative abundance of proteins that drive production of the drug-sequestering matrix. Turbinmicin displays a new dual...

Routine susceptibility testing often misses resistance in bla(OXA-1)-producing E. coli, risking therapeutic failure. Among 165 clinical isolates from the Spanish multicenter cohort, MicroScan and disk diffusion versus reference broth microdilution yielded suboptimal categorical agreement (73.9%-86.7%) for piperacillin-tazobactam (PTZ) and cefepime (FEP). MicroScan PTZ very major errors (30%) indicate resistance underestimation; disk diffusion PTZ major errors (23%) and both methods FEP major...

Obeldesivir (GS-5245, ODV), an orally administered 5'-isobutyryl ester prodrug of GS-441524, has demonstrated anti-SARS-CoV-2 activity in preclinical and clinical settings. ODV is hydrolyzed in plasma to provide high systemic exposures of GS-441524, enabling the efficient intracellular formation of the bioactive 5'-triphosphate GS-443902, an ATP analog inhibiting the SARS-CoV-2 RNA-dependent RNA polymerases. Remdesivir (RDV), the first US FDA-approved antiviral treatment for COVID-19, is also...