Genetic Determinants Required for Biofilm Formation by Acinetobacter baumannii

Autor: Tomaras, Andrew P.
Jazyk: angličtina
Rok vydání: 2004
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Popis: Acinetobacter baumannii is an important human pathogen that causes severe respiratory diseases in compromised patients. This bacterium is capable of surviving on nutrient-limited abiotic surfaces, such as bed linens, hospital equipment, and medical devices. This survival property suggested the possibility that this pathogen could form biofilms to survive such unfavorable conditions. Biofilms are aggregates of bacterial cells that are metabolically and physiologically distinct from their planktonic counterparts. Cells composing these structures work together to acquire nutrients and survive harsh environmental conditions. This hypothesis was proven by observing biofilm formation by A. baumannii on abiotic surfaces such as plastics. This formation seems to occur independently of cell motility, as we have been unable to detect such a capability in this organism. Random insertion mutagenesis revealed the presence of a chaperone-usher secretion system, which was found to be involved in the assembly of pili on the bacterial cell surface. These pili are essential for attachment and subsequent biofilm formation on abiotic surfaces, and are assembled using a cellular machinery similar to that described previously in other gram-negative pathogenic organisms. The same mutagenesis approach allowed for the discovery of a putative two-component regulatory system, which is also involved in this attachment process. Interestingly, this regulatory circuit controls pili production by activating the transcription of the chaperone-usher system described above. Additionally, this regulatory system controls cellular morphology in a nutrient-dependent fashion. The ability of A. baumannii to form biofilms on biotic surfaces was also tested in this work. It was found that this organism could attach to two distinct biotic surfaces, Candida albicans and HeLa cells, and that the presence of pili on the bacterial cell surface was not as essential to attachment as it was for abiotic surface colonization. In addition, the successful binding of A. baumannii cells to either biotic surface led to the death of either eukaryotic cell type. Therefore, our results demonstrate that the abiotic and biotic systems described in this work can be used to identify the virulence factors produced by A. baumannii to cause serious human infections.
Databáze: Networked Digital Library of Theses & Dissertations