ModernAcinetobacter baumanniiclinical isolates replicate inside spacious vacuoles and egress from macrophages

Autor: Le Nguyen-Hung, Mariana G Sartorio, Mario F. Feldman, Gisela Di Venanzio, Nichollas E. Scott, Wandy L. Beatty, Gabriela Sycz
Rok vydání: 2021
Předmět:
DOI: 10.1101/2021.04.08.439081
Popis: Multidrug-resistantAcinetobacter baumanniiinfections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat theseA. baumanniiinfections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pathobiology, which remains poorly understood.A. baumanniiis regarded as an extracellular opportunistic pathogen. However, research onAcinetobacterhas largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modernA. baumanniiclinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication ofA. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance ofA. baumannii.
Databáze: OpenAIRE