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2022-09-15Zeitschriftenartikel
An Unprecedented Tolerance to Deletion of the Periplasmic Chaperones SurA, Skp, and DegP in the Nosocomial Pathogen Acinetobacter baumannii
dc.contributor.authorBirkle, Karolin
dc.contributor.authorRenscher, Fabian
dc.contributor.authorAngelov, Angel
dc.contributor.authorWilharm, Gottfried
dc.contributor.authorFranz-Wachtel, Mirita
dc.contributor.authorMaček, Boris
dc.contributor.authorBohn, Erwin
dc.contributor.authorWeber, Elena
dc.contributor.authorMüller, Jennifer
dc.contributor.authorFriedrich, Lea
dc.contributor.authorSchütz, Monika
dc.date.accessioned2024-09-20T13:55:12Z
dc.date.available2024-09-20T13:55:12Z
dc.date.issued2022-09-15none
dc.identifier.other10.1128/jb.00054-22
dc.identifier.urihttp://edoc.rki.de/176904/12255
dc.description.abstractThe outer membrane (OM) of Gram-negative bacteria efficiently protects from harmful environmental stresses such as antibiotics, disinfectants, or dryness. The main constituents of the OM are integral OM β-barrel proteins (OMPs). In Gram-negative bacteria such as Escherichia coli, Yersinia enterocolitica, and Pseudomonas aeruginosa, 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 E. coli, Y. enterocolitica, and P. aeruginosa, the deletion of SurA is particularly detrimental and leads to a loss of OM integrity, sensitization to antibiotic treatment, and reduced virulence. In search of targets that could be exploited to develop compounds that interfere with OM integrity in Acinetobacter baumannii, we employed the multidrug-resistant strain AB5075 to generate single gene knockout strains lacking individual periplasmic chaperones. In contrast to E. coli, Y. enterocolitica, and P. aeruginosa, AB5075 tolerates the lack of SurA, Skp, or DegP with only weak mutant phenotypes. While the double knockout strains ΔsurAΔskp and ΔsurAΔdegP are conditionally lethal in E. coli, all double deletions were well tolerated by AB5075. Strikingly, even a triple-knockout strain of AB5075, lacking surA, skp, and degP, was viable. IMPORTANCE Acinetobacter baumannii is a major threat to human health due to its ability to persist in the hospital environment, resistance to antibiotic treatment, and ability to deploy multiple and redundant virulence factors. In a rising number of cases, infections with multidrug-resistant A. baumannii end up fatally, because all antibiotic treatment options fail. Thus, novel targets have to be identified and alternative therapeutics have to be developed. The knockout of periplasmic chaperones has previously proven to significantly reduce virulence and even break antibiotic resistance in other Gram-negative pathogens. Our study in A. baumannii demonstrates how variable the importance of the periplasmic chaperones SurA, Skp, and DegP can be and suggests the existence of mechanisms allowing A. baumannii to cope with the lack of the three periplasmic chaperones.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectacinetobacter baumanii AB075eng
dc.subjectperiplasmic chaperoneseng
dc.subjectSurAeng
dc.subjectOMP biogenesiseng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleAn Unprecedented Tolerance to Deletion of the Periplasmic Chaperones SurA, Skp, and DegP in the Nosocomial Pathogen Acinetobacter baumanniinone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/12255-9
dc.type.versionpublishedVersionnone
local.edoc.container-titleJournal of Bacteriologynone
local.edoc.container-issn1098-5530none
local.edoc.pages21none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://journals.asm.org/journal/jbnone
local.edoc.container-publisher-nameAmerican Society for Microbiologynone
local.edoc.container-volume204none
local.edoc.container-issue10none
local.edoc.container-reportyear2022none
dc.description.versionPeer Reviewednone

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