Acapsular Staphylococcus aureus with a non-functional agr regains capsule expression after passage through the bloodstream in a bacteremia mouse model.

Autor: Suligoy CM; Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM UBA-CONICET), Buenos Aires, Argentina., Díaz RE; Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM UBA-CONICET), Buenos Aires, Argentina., Gehrke AK; Departamento de Investigaciones Biomédicas y Biotecnológicas, Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico (CEBBAD), Universidad Maimónides and CONICET, Buenos Aires, Argentina., Ring N; The Roslin Institute, Royal (Dick) School of Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, UK., Yebra G; The Roslin Institute, Royal (Dick) School of Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, UK., Alves J; The Roslin Institute, Royal (Dick) School of Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, UK., Gómez MI; Departamento de Investigaciones Biomédicas y Biotecnológicas, Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico (CEBBAD), Universidad Maimónides and CONICET, Buenos Aires, Argentina., Wendler S; Institute of Medical Microbiology, Jena University Hospital, Jena, Germany., Fitzgerald JR; The Roslin Institute, Royal (Dick) School of Veterinary Medicine, University of Edinburgh, Easter Bush Campus, Edinburgh, UK., Tuchscherr L; Institute of Medical Microbiology, Jena University Hospital, Jena, Germany., Löffler B; Institute of Medical Microbiology, Jena University Hospital, Jena, Germany., Sordelli DO; Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM UBA-CONICET), Buenos Aires, Argentina. dsordelli@yahoo.com., Llana MN; Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM UBA-CONICET), Buenos Aires, Argentina., Buzzola FR; Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM UBA-CONICET), Buenos Aires, Argentina.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Aug 24; Vol. 10 (1), pp. 14108. Date of Electronic Publication: 2020 Aug 24.
DOI: 10.1038/s41598-020-70671-1
Abstrakt: Selection pressures exerted on Staphylococcus aureus by host factors during infection may lead to the emergence of regulatory phenotypes better adapted to the infection site. Traits convenient for persistence may be fixed by mutation thus turning these mutants into microevolution endpoints. The feasibility that stable, non-encapsulated S. aureus mutants can regain expression of key virulence factors for survival in the bloodstream was investigated. S. aureus agr mutant HU-14 (IS256 insertion in agrC) from a patient with chronic osteomyelitis was passed through the bloodstream using a bacteriemia mouse model and derivative P3.1 was obtained. Although IS256 remained inserted in agrC, P3.1 regained production of capsular polysaccharide type 5 (CP5) and staphyloxanthin. Furthermore, P3.1 expressed higher levels of asp23/SigB when compared with parental strain HU-14. Strain P3.1 displayed decreased osteoclastogenesis capacity, thus indicating decreased adaptability to bone compared with strain HU-14 and exhibited a trend to be more virulent than parental strain HU-14. Strain P3.1 exhibited the loss of one IS256 copy, which was originally located in the HU-14 noncoding region between dnaG (DNA primase) and rpoD (sigA). This loss may be associated with the observed phenotype change but the mechanism remains unknown. In conclusion, S. aureus organisms that escape the infected bone may recover the expression of key virulence factors through a rapid microevolution pathway involving SigB regulation of key virulence factors.
Databáze: MEDLINE
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