A Universal Stress Protein upregulated by hypoxia may contribute to chronic lung colonisation and intramacrophage survival in cystic fibrosis

Abstract

SummaryUniversal stress proteins (USPs) are ubiquitously expressed in bacteria, plants and eukaryotes and play a lead role in adaptation to environmental conditions. In Gram negative bacteria they enable adaption of bacterial pathogens to the conditions encountered in the human niche, including hypoxia, oxidative stress, osmotic stress, nutrient deficiency or acid stress, thereby facilitating colonisation. We previously reported that all six USP proteins encoded within a low-oxygen responsive locus in Burkholderia cenocepacia showed increased abundance during chronic colonisation of the CF lung. However, the role of USPs in chronic infection is not known. Using mutants derived from B. cenocepacia strain, K56-2, we show that USP76 is required for growth and survival in many conditions associated with the CF lung including, hypoxia, acidic conditions, oxidative stress. Moreover, it is involved in attachment to host epithelial cells, but not virulence. It also has a role in survival in macrophages isolated from people with CF. In contrast, another USP encoded in the same locus, USP92 had no effect on host cell attachment or oxidative stress, but was responsible for a 3-fold increase in virulence. Overall this shows that these USPs, both upregulated during chronic infection, have distinct roles in Burkholderia pathogenesis and may support the survival of B. cenocepacia in the CF lung. Specifically, USP76 is involved in its survival within CF macrophages, a hallmark of Burkholderia infection.

Parasite Survival and Disease Persistence in Cystic Fibrosis, Schistosomiasis and Pathogenic Bacterial Diseases: A Role for Universal Stress Proteins?

“…Burkholderia cepacia complex (Bcc) is an opportunistic pathogen not only present among CF patients but also in immunocompromised individuals, pharmaceutical plants, products and disinfectants, whose eradication becomes difficult to undertake once colonization has been established [ 54 ]. B. cenocepacia , one of the B. cepacia strains, is considered more virulent than P. aeruginosa because it is associated with a terminal illness known as “cepacia syndrome” that is typified by high temperatures, septicemia, confluent bronchopneumonia and a general decline in pulmonary function, which leads to patient death within days of infection in comparison to the months after which P. aeruginosa patients eventually succumb to it [ 55 , 56 ].…”

“…All the proteins exhibited an increase (of up to 40-fold) in production during chronic lung infection. Subsequent studies then showed that Usp76 and Usp92 displayed different functions showcasing the functional variety of these proteins [ 54 ]. Usp76 was, however, highlighted as the most significant contributor to B. cenocepacia survival owing to the changes in phenotype observed in Δusp76 mutants in comparison to the wild type and its role in protecting against oxidative stress and attachment to host cells in comparison to Usp92.…”

Comprehensive Analysis of Universal Stress Protein Family Genes and Their Expression in Fusarium oxysporum Response of Populus davidiana × P. alba var. pyramidalis Louche Based on the Transcriptome

“…Universal stress proteins (USPs) were first discovered in 1990 [ 1 , 2 ]. They are typical stress-inducible proteins that are essential in various cellular responses under biotic or abiotic stress conditions such as nutrient deficiency [ 3 ], heat or cold stimulation [ 4 ], oxidative stress [ 5 ], and osmotic stress [ 4 ].…”