The role of the periplasmic chaperones SurA, Skp and DegP for fitness, outer membrane integrity, antibiotic susceptibility and virulence of Acinetobacter baumannii AB5075: same-same, but different?

ABSTRACT: The outer membrane (OM) of Gram-negative bacteria efficiently protects from harmful environmental stresses such as antibiotics, disinfectants or dryness. Main constituents of the OM are integral OM β-barrel proteins (OMPs). In Gram-negative bacteria such as Escherichia coli (Ec), Yersinia enterocolitica (Ye) and Pseudomonas aeruginosa (Pa), the insertion of OMPs depends on a sophisticated biogenesis pathway. This comprises the SecYEG translocon, which enables inner membrane (IM) passage, the chaperones SurA, Skp and DegP, which facilitate the passage of β-barrel OMPs through the periplasm, and the β-barrel assembly machinery (BAM) which facilitates insertion into the OM. In Ec, Ye and Pa the deletion of SurA is particularly detrimental and leads to a loss of OM integrity, sensitization to antibiotics, and hypovirulence. In search of targets that could be exploited to develop compounds that interfere with OM integrity in Acinetobacter baumannii (Ab), we employed the multidrug-resistant strain AB5075 to generate single gene knockout strains lacking individual periplasmic chaperones. In contrast to Ec, Ye and Pa, AB5075 tolerates the lack of SurA, Skp or DegP with only weak mutant phenotypes. While the double knockout strains surAskp and surAdegP are conditionally lethal in Ec, all double deletions were well tolerated by AB5075. Strikingly, even a triple knockout strain of AB5075, lacking surA, skp and degP, was viable. Our findings underline the extreme adaptibility of Ab and suggest the existence of mechanisms bypassing or acting redundantly to the known OMP biogenesis pathway comprising SurA, Skp and DegP.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Acinetobacter Baumannii

SUBMITTER: Nicolas Nalpas  

LAB HEAD: Monika Schütz

PROVIDER: PXD022004 | Pride | 2022-08-29

REPOSITORIES: Pride