Survival protein A is essential for virulence in Yersinia pestis

Abstract

Plague is a highly pathogenic disease caused by the bacterium Yersinia pestis. There is currently no vaccine available for prophylaxis and antibiotic resistant strains have been isolated, thus there is a need for the development of new countermeasures to treat this disease. Survival protein A (SurA) is a chaperone that has been linked to virulence in several species of bacteria, including the close relative Yersinia pseudotuberculosis. In this study, we aimed to evaluate the role of SurA in virulence of the highly pathogenic Y. pestis by creating an unmarked surA deletion mutant. The Y. pestis ΔsurA mutant was found to be more susceptible to membrane perturbing agents and was completely avirulent in a mouse infection model when delivered up to 2.1 × 10(5) CFU by the subcutaneous route. This provides strong evidence that SurA would make a promising antimicrobial target.

Identifying components required for OMP biogenesis as novel targets for antiinfective drugs

“… 62,75 A key role of SurA for virulence was reported also for Salmonella enterica , 76,77 Shigella flexneri , 78 uropathogenic E. coli , 79,80 Yersinia pseudotuberculosis 15,81 and Yersinia pestis . 82 Thus the spectrum of pathogens that could be treated by new drugs that aim at reduction of virulence and impairment of OM barrier could be extended or adapted to a large range of Gram-negatives. In fact, the sequence homology of BamB and SurA in a variety of enteropathogens is quite high, particularly in the family of Enterobacteriaceae comprising e.g.…”

Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria

“…In Yersinia sp. the σ E -regulated chaperone SurA is required for Y. pseudotuberculosis adhesion to HeLa cells (Obi and Francis, 2013) and a Y. pestis surA mutant is attenuated in mice (Southern et al, 2016). The vast array of studies highlighted in this review demonstrate that σ E is of extreme importance to not only survival of Gram-negative bacteria, through the maintenance of the extracytoplasmic OM, but also to the ability to cause such successful and varied infections.…”

Environmental Regulation of Yersinia Pathophysiology

“…SurA is implicated in most phenotypic characteristics associated with this protein family (Behrens-Kneip, 2010 ). In Yersinia lacking the surA allele, outer membrane perturbations result that include aberrant cellular morphology, drastic alterations in OMP profile, susceptibility to detergents and antibiotics, altered fatty acid and phospholipid composition and leakiness of LPS into the extracellular environment (Obi et al, 2011 ; Southern et al, 2015 ). Not surprisingly therefore, the SurA PPIase and chaperone is essential for the virulence of Yersinia in a mouse infection models (Obi et al, 2011 ; Southern et al, 2015 ).…”

“…In Yersinia lacking the surA allele, outer membrane perturbations result that include aberrant cellular morphology, drastic alterations in OMP profile, susceptibility to detergents and antibiotics, altered fatty acid and phospholipid composition and leakiness of LPS into the extracellular environment (Obi et al, 2011 ; Southern et al, 2015 ). Not surprisingly therefore, the SurA PPIase and chaperone is essential for the virulence of Yersinia in a mouse infection models (Obi et al, 2011 ; Southern et al, 2015 ). Critically though, SurA + Yersinia are also avirulent if they lack all four remaining periplasmic PPIases (i.e., PpiA, PpiD, FkpA, and FklB) (Obi et al, 2011 ).…”