Explore the vast range of titles available.

Daptomycin is one of the few remaining effective antibiotics for treating vancomycin-resistant enterococcal infections but is limited by the emergence of resistance during protracted therapy. Here, we show that without a functional lafB gene, daptomycin-resistant mutants do not arise under conditions where wild-type strains readily generate daptomycin-resistant mutants. Furthermore, we show that loss of function mutation of the lafB gene in daptomycin-resistant clinical isolates renders them more susceptible to daptomycin than wild-type Enterococcus faecium . This indicates that an effective small molecule inhibitor of LafB activity or lafB gene expression would be a useful adjunctive for extending and restoring the therapeutic utility of daptomycin.

Antibiotic-resistant Pseudomonas aeruginosa is a major clinical challenge due to limited drug uptake. This study shows that exogenous glutamate restores gentamicin efficacy by reprogramming bacterial metabolism to enhance membrane permeability. The effect is mediated through increased biosynthesis of unsaturated fatty acids, which is further confirmed by oleic acid supplementation. These findings reveal a novel metabolic approach to overcome multidrug and carbapenem resistance, offering a promising adjunct strategy to improve antibiotic treatment outcomes.

The global crisis of antimicrobial resistance demands innovative strategies to revitalize existing antibiotics. Our work addresses this urgent need by demonstrating that L-arginine acts as a powerful potentiator of chloramphenicol, enhancing its bactericidal efficacy by over 100-fold against multidrug-resistant Edwardsiella tarda . More significantly, we elucidate a novel, dual-pathway mechanism: arginine concurrently disrupts the TCA cycle and phenylalanine metabolism, which collectively alter the cellular redox state and compromise the proton motive force. This study is the first to uncover this sophisticated metabolic interplay, providing not only a promising adjuvant strategy but also a new conceptual framework for combating resistant bacterial infections by targeting core metabolism. Our findings, therefore, hold substantial potential for both basic science and translational antimicrobial development.

Understanding the structure and function of efflux pumps is crucial for addressing efflux-mediated resistance. Transporters that pump out biocides or heavy metals are not uncommon. However, to date, no transport protein capable of extruding both types of substrates has been reported. Initially, it was proposed that Klebsiella pneumoniae CepA was associated with chlorhexidine resistance and subsequently considered a biocide efflux pump. That notion also hinted at a novel group of drug efflux pumps that can extrude both biocides and heavy metals, a direct mechanism of cross-resistance between the two. The findings of this study indicate that it is more plausible that K. pneumoniae CepA is involved in metal homeostasis rather than in chlorhexidine biocide resistance in the recombinant Escherichia coli .

Infections caused by carbapenem-resistant Enterobacterales (CRE) pose significant threats to patients and public health worldwide. Carbapenem resistance can occur through several molecular mechanisms, including enzymatic hydrolysis by carbapenemases and reduced influx via porin mutations. Identifying carbapenemase-producing isolates could enable tailored antibiotic selection to improve patient outcomes and infection control measures to prevent further carbapenemase transmission. In a large collection of CRE isolates, we found that only carbapenemase-producing CRE exhibited an inoculum effect, in which their measured resistance varies markedly with cell density, which risks misdiagnosis. Further, this inoculum effect occurred under conditions where bacteria released carbapenemases to the community upon exposure to antibiotics that resulted in cell death. Measuring this inoculum effect, or integrating other data from routine antimicrobial susceptibility testing, enhanced carbapenem resistance detection, paving the way for more effective strategies to combat this growing public health crisis.

The ability of bacteria such as Klebsiella pneumoniae and Escherichia coli to circumvent antimicrobial chemotherapy has become a global public health crisis. The high prevalence of β-lactamase enzymes capable of rendering our most prescribed antibiotics, the β-lactams (BLs) inactive, has left us with few available treatment options against infections caused by these bacteria. The use of small molecules that inhibit especially serine β-lactamases has substantially prolonged the lifetime of BL antibiotics. Yet, most clinically available inhibitors either do not possess or have limited ability to reverse resistance conferred by metallo-β-lactamase (MBL) enzymes. Combining chelator and transition state analog technology, our hybrid compound restores the effectiveness of BL antibiotics in cases of resistance conferred by both serine β-lactamases (SBLs) and MBLs. Our approach of covalently combining a chelator with an existing SBL inhibitor scaffold offers a promising solution for managing life-threatening infections and prolonging the use of clinically available BLs.

A significant opportunistic pathogen, Acinetobacter baumannii (A. baumannii) has evolved mechanisms of resistance to a wide variety of antimicrobials, including carbapenems. In this article, we assessed the prevalence, risk factors, antimicrobial sensitivity, and resistance mechanisms among A. baumannii in several locations in Saudi Arabia. Hospital-acquired infections caused by A. baumannii were prevalent in the country due to a variety of reasons, such as the high number of critically ill patients, the frequency of gastrointestinal colonization, and the widespread use of antimicrobial medications. There has been an increase in the frequency of A. baumannii strains that are resistant to several antimicrobials, including carbapenems. Hospitals are a breeding ground for multidrug-resistant A. baumannii due to the widespread use of broad-spectrum antibiotics, the potential for patient-to-patient transmission of the bacteria, the high risk of infection during invasive intensive care unit procedures, and the high frequency with which diabetic and cancer patients in hospitals undergo invasive diagnostic and therapeutic procedures. Combinations of colistin and tigecycline with carbapenems or other antibiotics remain the best treatment option and are relatively safe to treat patients with multidrug resistance (MDR) A. baumannii infections, despite the rising incidence of resistance to these drugs observed in many hospitals. The prevalence of multidrug-resistant A. baumannii in Saudi hospitals calls for in-depth research into the underlying molecular mechanisms of multidrug resistance. In addition, a better understanding of A. baumannii resistance patterns and the establishment of a treatment protocol to reduce the infection burden in Saudi Arabia could benefit from the implementation of a local antibiogram database in tandem with a national antimicrobial stewardship and infection prevention program.

Antibiotics are among the most important discoveries of the 20th century, having saved millions of lives from infectious diseases. Microbes have developed acquired antimicrobial resistance (AMR) to many drugs due to high selection pressure from increasing use and misuse of antibiotics over the years. The transmission and acquisition of AMR occur primarily via a human–human interface both within and outside of healthcare facilities. A huge number of interdependent factors related to healthcare and agriculture govern the development of AMR through various drug-resistance mechanisms. The emergence and spread of AMR from the unrestricted use of antimicrobials in livestock feed has been a major contributing factor. The prevalence of antimicrobial-resistant bacteria has attained an incongruous level worldwide and threatens global public health as a silent pandemic, necessitating urgent intervention. Therapeutic options of infections caused by antimicrobial-resistant bacteria are limited, resulting in significant morbidity and mortality with high financial impact. The paucity in discovery and supply of new novel antimicrobials to treat life-threatening infections by resistant pathogens stands in sharp contrast to demand. Immediate interventions to contain AMR include surveillance and monitoring, minimizing over-the-counter antibiotics and antibiotics in food animals, access to quality and affordable medicines, vaccines and diagnostics, and enforcement of legislation. An orchestrated collaborative action within and between multiple national and international organizations is required urgently, otherwise, a postantibiotic era can be a more real possibility than an apocalyptic fantasy for the 21st century. This narrative review highlights on this basis, mechanisms and factors in microbial resistance, and key strategies to combat antimicrobial resistance.

The global rise of vancomycin-resistant enterococci (VRE) poses serious challenges in clinical treatment due to limited therapeutic options and rapid resistance development. This study identifies bunamidine hydrochloride (BUN), a previously approved antiparasitic agent, as a potent membrane-targeting antimicrobial with rapid bactericidal activity against both planktonic and biofilm-associated VRE. By selectively interacting with bacterial phosphatidylglycerol, BUN disrupts membrane integrity and inhibits persister cells, while maintaining low cytotoxicity and high in vivo efficacy in murine infection models. Our findings highlight the potential of drug repurposing strategies to accelerate the discovery of effective antibiotics and provide a promising candidate for future clinical management of multidrug-resistant bacterial infections.

Candidozyma auris is a global human health threat because of its near-universal resistance to the antifungal fluconazole as well as a predisposition to multidrug resistance among clinical isolates. The underlying mechanisms of antifungal drug resistance in this species are still largely under investigation, and these efforts are significantly supported by research that increase our understanding of unique aspects of C. auris biology. We have identified a correlation between C. auris isolates’ susceptibility to fluconazole and intracellular drug accumulation in which drug-resistant isolates have significantly reduced intracellular fluconazole compared to isolates that are susceptible to fluconazole. We have proposed a mechanism for this phenomenon and demonstrated important roles for mutations in ERG11, TAC1B, and CDR1 gene sequences for drug resistance.