Achromobacter xylosoxidans Cellular Pathology Is Correlated with Activation of a Type III Secretion System

Abstract

Achromobacter xylosoxidans is increasingly recognized as a colonizer of cystic fibrosis (CF) patients, but the role that A. xylosoxidans plays in pathology remains unknown. This knowledge gap is largely due to the lack of model systems available to study the toxic potential of this bacterium. Recently, a phospholipase A2 (PLA2) encoded by a majority of A. xylosoxidans genomes, termed AxoU, was identified. Here, we show that AxoU is a type III secretion system (T3SS) substrate that induces cytotoxicity to mammalian cells. A tissue culture model was developed showing that a subset of A. xylosoxidans isolates from CF patients induce cytotoxicity in macrophages, suggestive of a pathogenic or inflammatory role in the CF lung. In a toxic strain, cytotoxicity is correlated with transcriptional activation of axoU and T3SS genes, demonstrating that this model can be used as a tool to identify and track expression of virulence determinants produced by this poorly understood bacterium.

Achromobacter xylosoxidans and Stenotrophomonas maltophilia: Emerging Pathogens Well-Armed for Life in the Cystic Fibrosis Patients’ Lung

“…T3SS and T6SS mediate an effector transport by direct contact with the target cells [ 64 ] and T6SS has been shown to deliver lethal toxins into bacterial cells [ 65 , 66 ]. A complete T3SS locus has been observed in 72% of the 65 Axc genomes examined [ 67 ]. An important T3SS substrate is the phospholipase A2 AxoU, similar to the ExoU of P. aeruginosa , encoded by 98% of T3SS-positive Axc strains [ 67 , 68 ].…”

“…A complete T3SS locus has been observed in 72% of the 65 Axc genomes examined [ 67 ]. An important T3SS substrate is the phospholipase A2 AxoU, similar to the ExoU of P. aeruginosa , encoded by 98% of T3SS-positive Axc strains [ 67 , 68 ]. AxoU exhibits toxicity against eukaryotic cells by cleavage of membrane phospholipids, leading to lysis of the host cells, particularly phagocytic cells, and inhibits the innate immune response [ 67 , 68 ].…”

“…An important T3SS substrate is the phospholipase A2 AxoU, similar to the ExoU of P. aeruginosa , encoded by 98% of T3SS-positive Axc strains [ 67 , 68 ]. AxoU exhibits toxicity against eukaryotic cells by cleavage of membrane phospholipids, leading to lysis of the host cells, particularly phagocytic cells, and inhibits the innate immune response [ 67 , 68 ]. AxoU/T3SS-mediated cytotoxicity should thus be considered as an important virulence trait of Axc ; however, further investigation is still required to fully elucidate this virulence mechanism, as bacterial internalization appears to be required for cytotoxicity [ 67 ].…”

“…AxoU exhibits toxicity against eukaryotic cells by cleavage of membrane phospholipids, leading to lysis of the host cells, particularly phagocytic cells, and inhibits the innate immune response [67,68]. AxoU/T3SS-mediated cytotoxicity should thus be considered as an important virulence trait of Axc; however, further investigation is still required to fully elucidate this virulence mechanism, as bacterial internalization appears to be required for cytotoxicity [67]. First of all, Axc and Sm harbor T2SS, which contributes to virulence in many pathogens; as examples, T2SS-dependent substrates include the cholera toxin from Vibrio cholerae and exotoxin A from P. aeruginosa [51].…”

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“…выявляют гены систем секреции 3 и 6 типов, гены основной субъединицы пилей yagZ/ ecpA, гены ферментов синтеза пиоцианина и пиовер дина [10]. Появляются сообщения о новых факторах вирулентности у Achromobacter xylosoxidans, таких как колицин V, фосфолипаза C, экзотоксин AxoU [3,11]. Опасность Achromobacter spp.…”