Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.

A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance.

Mechanistic Studies and Efficacy of an Oxadiazole-Containing Antibiotic.

Methicillin-resistant (MRSA) infections are still difficult to treat, despite the availability of many FDA-approved antibiotics. Thus, new compound scaffolds are still needed to treat MRSA. The oxadiazole-containing compound, , has been shown to reduce lipoteichoic acid (LTA) in , but the mechanism that accounts for LTA biosynthesis inhibition remains uncharacterized.

Comparative Studies to Uncover Mechanisms of Action of -(1,3,4-Oxadiazol-2-yl)benzamide Containing Antibacterial Agents.

Drug-resistant bacterial pathogens still cause high levels of mortality annually despite the availability of many antibiotics. Methicillin-resistant (MRSA) is especially problematic, and the rise in resistance to front-line treatments like vancomycin and linezolid calls for new chemical modalities to treat chronic and relapsing MRSA infections. Halogenated -(1,3,4-oxadiazol-2-yl)benzamides are an interesting class of antimicrobial agents, which have been described by multiple groups to be effective against different bacterial pathogens.

Identification of a Cyclic Dinucleotide Phosphodiesterase Inhibitor.

Immune cells sense bacteria-derived c-di-GMP and c-di-AMP as well as host-derived cGAMP, which is synthesized by cGAS upon binding to the pathogen's DNA, to mount an immunological response (cytokine production) via the STING-TBK1 pathway. Successful pathogens, such as and group B streptococcus, harbor phosphodiesterases (PDEs) that can cleave bacterial c-di-AMP as well as host-derived cGAMP to blunt the host's response to infection. Selective inhibitors of bacterial cyclic dinucleotide (CDN) PDEs are needed as tool compounds to study the role(s) of CDN PDEs during infection and they could also become bona fide antivirulence compounds, but there is a paucity of such compounds.

Antibacterial Small Molecules That Potently Inhibit Staphylococcus aureus Lipoteichoic Acid Biosynthesis.

The rise of antibiotic resistance, especially in Staphylococcus aureus, and the increasing death rate due to multiresistant bacteria have been well documented. The need for new chemical entities and/or the identification of novel targets for antibacterial drug development is high. Lipoteichoic acid (LTA), a membrane-attached anionic polymer, is important for the growth and virulence of many Gram-positive bacteria, and interest has been high in the discovery of LTA biosynthesis inhibitors.

Antibiotic Susceptibility Determination within One Cell Cycle at Single-Bacterium Level by Stimulated Raman Metabolic Imaging.

The widespread use of antibiotics has significantly increased the number of resistant bacteria, which has also increased the urgency of rapid bacterial detection and profiling their antibiotic response. Current clinical methods for antibiotic susceptibility testing (AST) rely on culture and require at least 16 to 24 h to conduct. Therefore, there is an urgent need for a rapid method that can test the susceptibility of bacteria in a culture-free manner.

Stimulated Raman Imaging Reveals Aberrant Lipogenesis as a Metabolic Marker for Azole-Resistant Candida albicans.

Candida albicans is the single most prevalent cause of fungal bloodstream infections worldwide causing significant mortality as high as 50 percent. This high mortality rate is, in part, due to the inability to initiate an effective antifungal therapy early in the disease process. Mortality rates significantly increase after 12 hours of delay in initiating the appropriate antifungal therapy following a positive blood culture.