In Vitro Selection Identifies Staphylococcus aureus Genes Influencing Biofilm Formation

Staphylococcus aureus generates biofilms during many chronic human infections, which contributes to its growth and persistence in the host. Multiple genes and pathways necessary for S. aureus biofilm production have been identified, but knowledge is incomplete, and little is known about spontaneous mutations that increase biofilm formation as infection progresses. Here, we performed in vitro selection of four S. aureus laboratory strains (ATCC 29213, JE2, N315, and Newman) to identify mutations associated with enhanced biofilm production. Biofilm formation increased in passaged isolates from all strains, exhibiting from 1.2- to 5-fold the capacity of parental lines. Whole-genome sequencing identified nonsynonymous mutations affecting 23 candidate genes and a genomic duplication encompassing sigB. Six candidate genes significantly impacted biofilm formation as isogenic transposon knockouts: three were previously reported to impact S. aureus biofilm formation (icaR, spdC, and codY), while the remaining three (manA, narH, and fruB) were newly implicated by this study. Plasmid-mediated genetic complementation of manA, narH, and fruB transposon mutants corrected biofilm deficiencies, with high-level expression of manA and fruB further enhancing biofilm formation over basal levels. This work recognizes genes not previously identified as contributing to biofilm formation in S. aureus and reveals genetic changes able to augment biofilm production by that organism.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:91

Enthalten in:

Infection and immunity - 91(2023), 3 vom: 15. März, Seite e0053822

Sprache:

Englisch

Beteiligte Personen:

Long, Dustin R [VerfasserIn]
Penewit, Kelsi [VerfasserIn]
Lo, Hsin-Yu [VerfasserIn]
Almazan, Jared [VerfasserIn]
Holmes, Elizabeth A [VerfasserIn]
Bryan, Andrew B [VerfasserIn]
Wolter, Daniel J [VerfasserIn]
Lewis, Janessa D [VerfasserIn]
Waalkes, Adam [VerfasserIn]
Salipante, Stephen J [VerfasserIn]

Links:

Volltext

Themen:

Adaptation
Biofilm
Cystic fibrosis
Evolution
Genomics
Infection
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Staphylococcus aureus

Anmerkungen:

Date Completed 20.03.2023

Date Revised 30.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1128/iai.00538-22

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM353536083