The unusual mode of action of the polyketide glycoside antibiotic cervimycin C.

Cervimycins A-D are bis-glycosylated polyketide antibiotics produced by HKI 0179 with bactericidal activity against Gram-positive bacteria. In this study, cervimycin C (CmC) treatment caused a spaghetti-like phenotype in 168, with elongated curved cells, which stayed joined after cell division, and exhibited a chromosome segregation defect, resulting in ghost cells without DNA. Electron microscopy of CmC-treated (3 × MIC) revealed swollen cells, misshapen septa, cell wall thickening, and a rough cell wall surface.

Staphylococcus epidermidis bacteriocin A37 kills natural competitors with a unique mechanism of action.

Many bacteria produce antimicrobial compounds such as lantibiotics to gain advantage in the competitive natural environments of microbiomes. Epilancins constitute an until now underexplored family of lantibiotics with an unknown ecological role and unresolved mode of action. We discovered production of an epilancin in the nasal isolate Staphylococcus epidermidis A37.

Determination of Bacterial Membrane Impairment by Antimicrobial Agents.

The bacterial cytoplasmic membrane separates the cell from its environment and acts as a selective permeability barrier. In addition, it functions in energy conservation, transport, signaling, and biosynthesis processes. Antimicrobial agents disrupting these functions may lead to pleiotropic effects, including leakage of low molecular weight compounds such as ions, amino acids, and ATP and subsequent membrane depolarization.

Identification of 5-(Aryl/Heteroaryl)amino-4-quinolones as Potent Membrane-Disrupting Agents to Combat Antibiotic-Resistant Gram-Positive Bacteria.

Nosocomial infections caused by resistant Gram-positive organisms are on the rise, presumably due to a combination of factors including prolonged hospital exposure, increased use of invasive procedures, and pervasive antibiotic therapy. Although antibiotic stewardship and infection control measures are helpful, newer agents against multidrug-resistant (MDR) Gram-positive bacteria are urgently needed. Here, we describe our efforts that led to the identification of 5-amino-4-quinolone with exceptionally potent Gram-positive activity with minimum inhibitory concentrations (MICs) ≤0.

Cervimycin-Resistant Staphylococcus aureus Strains Display Vancomycin-Intermediate Resistant Phenotypes.

Resistance to antibiotics is an increasing problem and necessitates novel antibacterial therapies. The polyketide antibiotics cervimycin A to D are natural products of Streptomyces tendae HKI 0179 with promising activity against multidrug-resistant staphylococci and vancomycin-resistant enterococci. To initiate mode of action studies, we selected cervimycin C- and D-resistant (CmR) Staphylococcus aureus strains.