Extracellular biofilm matrix leads to microbial dysbiosis and reduces biofilm susceptibility to antimicrobials on titanium biomaterial: An in vitro and in situ study.
OBJECTIVES
To test the role of exopolysaccharide (EPS) polymers matrix to modulate the composition/virulence of biofilms growing on titanium (Ti) surfaces, the effect on antibiotic susceptibility, and whether a dual-targeting therapy approach for disrupted EPS matrix could improve the antimicrobial effect.


MATERIALS AND METHODS
A microcosm biofilm model using human saliva as inoculum was used, and the microbial composition was assessed by checkerboard DNA-DNA hybridization. EPS-enriched biofilms virulence was tested using fibroblast monolayer. Povidone-iodine (PI) was used as EPS-targeting agent followed by amoxicillin + metronidazole antibiotic to reduce bacterial biomass using an in situ model.


RESULTS
An EPS-enriched environment, obtained by sucrose exposure, promoted bacterial accumulation and led to a dysbiosis on biofilms, favoring the growth of Streptococcus, Fusobacterium, and Campylobacter species and even strict anaerobic species related to peri-implant infections, such as Porphyromonas gingivalis and Tannerella forsythia (~3-fold increase). EPS-enriched biofilm transitioned from a commensal aerobic to a pathogenic anaerobic profile. EPS increased biofilm virulence promoting higher host cell damage and reduced antimicrobial susceptibility, but the use of a dual-targeting approach with PI pre-treatment disrupted EPS matrix scaffold, increasing antibiotic effect on in situ biofilms.


CONCLUSION
Altogether, our data provide new insights of how EPS matrix creates an environment that favors putative pathogens growth and shed light to a promising approach that uses matrix disruption as initial step to potentially improve implant-related infections treatment.
['Costa|Raphael Cavalcante|RC|https://orcid.org/0000-0002-2684-5488', 'Souza|João Gabriel Silva|JGS|https://orcid.org/0000-0001-5944-6953', 'Bertolini|Martinna|M|https://orcid.org/0000-0003-3619-6618', 'Retamal-Valdes|Belén|B|https://orcid.org/0000-0003-1444-991X', 'Feres|Magda|M|https://orcid.org/0000-0002-2293-3392', 'Barão|Valentim A R|VAR|https://orcid.org/0000-0002-6391-9917']
D018441:Biofilms D064806:Dysbiosis D000077317:Extracellular Polymeric Substance Matrix D006801:Humans D013295:Streptococcus mutans D014025:Titanium
biofilms titanium biomaterials antibiotic microbiology