Transposon-sequencing across multiple isolates reveals significant functional genomic diversity among strains.

Unlabelled: ) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in have been primarily performed on reference strains. Given the growing public health threat of infections, understanding the functional genomic differences among clinical isolates can provide more insight into how its genetic diversity influences gene essentiality, clinically relevant phenotypes, and importantly, potential drug targets.

Durlobactam in combination with β-lactams to combat .

() presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies.

Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance in .

is a pulmonary pathogen that exhibits intrinsic resistance to antibiotics, but the factors driving this resistance are incompletely understood. Insufficient intracellular drug accumulation could explain broad-spectrum resistance, but whether antibiotics fail to accumulate in and the mechanisms required for drug exclusion remain poorly understood. We measured antibiotic accumulation in using mass spectrometry and found a wide range of drug accumulation across clinically relevant antibiotics.

Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System.

Background: Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections.

Objective: To describe the analysis and mitigation of a cluster of infections in cardiac surgery patients.

Design: Descriptive study.

Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection.

Mycobacterium abscessus is an emerging pathogen causing lung infection predominantly in patients with underlying structural abnormalities or lung disease and is resistant to most frontline antibiotics. As the pathogenic mechanisms of M. abscessus in the context of the lung are not well-understood, we developed an infection model using air-liquid interface culture and performed a transposon mutagenesis and sequencing screen to identify genes differentially required for bacterial survival in the lung.

Reporter Assays for Ebola Virus Nucleoprotein Oligomerization, Virion-Like Particle Budding, and Minigenome Activity Reveal the Importance of Nucleoprotein Amino Acid Position 111.

For highly pathogenic viruses, reporter assays that can be rapidly performed are critically needed to identify potentially functional mutations for further study under maximal containment (e.g., biosafety level 4 [BSL-4]).

Parallel Evolution of Host-Attachment Proteins in Phage PP01 Populations Adapting to O157:H7.

The emergence of antibiotic resistance has sparked interest in phage therapy, which uses virulent phages as antibacterial agents. Bacteriophage PP01 has been studied for potential bio-control of O157:H7, its natural host, but in the laboratory, PP01 can be inefficient at killing this bacterium. Thus, the goal of this study was to improve the therapeutic potential of PP01 through short-term experimental evolution.