Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii

Abstract

Abstract Acinetobacter baumanniihas emerged as one of the most common extensive drug resistant nosocomial bacterial pathogens that causes a diverse range of human infections. Not only can the bacteria survive in hospital settings for long periods, but they can also resist adverse conditions such as exposure to antimicrobial drugs and disinfectants and long-term desiccation. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediating its virulence are poorly understood. Here, we demonstrate that bi-stable expression of the Csu pili, along with the production of poly N-acetyl glucosamine, regulates the formation of mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and as pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells identified GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in type IV pili regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.