A new strategy of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus

As an aggressive pathogen, Staphylococcus aureus (S. aureus) poses a significant public health threat, and is becoming increasingly resistant to currently available antibiotics, including vancomycin, the drug of last resort against Gram-positive bacterial infection. S. aureus with intermediate level of resistance to vancomycin (vancomycin-intermediate S. aureus, VISA) was first identified in 1996. The resistance mechanism of VISA, however, has not been clarified, forcing us to solve this problem in order to control its spread. Here we show the occurrence of an anomalous diffusion of vancomycin through VISA cell wall, which is caused by cell wall clogging with vancomycin itself. The co-operative effect of the clogging and cell wall thickening leads VISA to obstruct vancomycin reaching its true target present in cytoplasmic membrane, exhibiting a new class of antibiotic resistance in Gram positive pathogens.