Both lactoferrin and iron influence aggregation and biofilm formation in Streptococcus mutans

Abstract

Streptococcus mutans, a gram-positive immobile bacterium, is an oral pathogen considered to be the principal etiologic agent of dental caries. Although some researches suggest that trace metals, including iron, can be associated with dental caries, the function of salivary iron and lactoferrin in the human oral cavity remains unclear. The data reported in this study indicates that iron-deprived saliva (Fe3+ < 0.1 microM) increases S. mutans aggregation and biofilm formation in the fluid and adherent phases as compared with saliva (Fe3+ from 0.1 to 1 microM), while iron-loaded saliva (Fe3+ > 1 microM) inhibits both phenomena. Our findings are consistent with the hypothesis that S. mutans aggregation and biofilm formation are negatively iron-modulated as confirmed by the different effect of bovine lactoferrin (bLf), added to saliva at physiological concentration (20 microg/ml) in the apo- or iron-saturated form. Even if saliva itself induces bacterial aggregation, iron binding capability of apo-bLf is responsible for the noticeable increase of bacterial aggregation and biofilm development in the fluid and adherent phases. On the contrary, iron-saturated bLf decreases aggregation and biofilm development by supplying iron to S. mutans. Therefore, the iron-withholding capability of apo-Lf or native Lf is an important signal to which S. mutans counteracts by leaving the planktonic state and entering into a new lifestyle, biofilm, to colonize and persist in the human oral cavity. In addition, another function of bLf, unrelated to its iron binding capability, is responsible for the inhibition of the adhesion of S. mutans free, aggregated or biofilm on abiotic surfaces. Both these activities of lactoferrin, related and unrelated to the iron binding capability, could have a key role in protecting the human oral cavity from S. mutans pathogenicity.

Discrete Responses to Limitation for Iron and Manganese in Agrobacterium tumefaciens: Influence on Attachment and Biofilm Formation

“…A major phenotype of interest for us is the ability of A. tumefaciens to attach to surfaces and form biofilms. Iron limitation has been demonstrated to influence biofilm formation in several other bacteria (31,36,68). The effects of iron limitation on the biofilm formation of A. tumefaciens were examined using static-culture biofilm assays with increasing concentrations of the iron chelator EDDHA and, in parallel, the commonly used iron chelator 2, 2=-dipyridyl (DIP).…”

“…Conversely, under static culture conditions, high iron levels appear to inhibit surface-associated biofilm formation by P. aeruginosa (34,35). In contrast, static biofilm formation by the oral pathogen Streptococcus mutans appears to be induced by the addition of lactoferrin and by iron limitation in general (36). In addition to altering iron availability, perturbation of P. aeruginosa iron-responsive regulators has a dramatic effect on biofilm formation.…”

Análise do sistema ativo de captação de glutamina de Streptococcus mutans.

“…Em relação ao S. mutans, estudos dos transportadores ABC restringem-se a transportadores de açúcar, metais, oligopeptídeos e aminoácidos (TAO et al, 1993;FRANCESCA et al, 2004;NEPOMUCENO et al;2007;DASHPER;RILEY;REYNOLDS, 1995). Em particular, a captação de glutamina nessa espécie está diretamente relacionada ao valor de pH intracelular e é estimulada pela presença de íons potássio (NOJI et al, 1988;SATO et al, 1989;DASHPER;RILEY;REYNOLDS, 1995 …”

Análise do papel dos transportadores ABC de oligopeptídeos, poliaminas, fosfato inorgânico, glutamato e glutamina na fisiologia e patogênese de bactérias do trato gastro-intestinal.

“…O transporte de fosfato inorgânico (Pi), em conjunto com o transporte de componentes organo-fosfatados, são essenciais para o controle e regulação interna da homeostase do fósforo, relacionado à fontes de energia, biossíntese de DNA, RNA e fofolipídeos ( VAN VEEN et al, 1993 Em relação ao S. mutans, estudos dos transportadores ABC restringem-se a transportadores de açúcar, metais, oligopeptídeos e aminoácidos (DASHPER et al, 1995;FRANCESCA et al, 2004;NEPOMUCENO et al, 2007;TAO et al, 1993a).…”

“…Sendo a capacidade de aderência/produção de biofilme a mais relevantes, por se tratar do passo inicial e essencial para o desenvolvimento da cárie dental, permitindo o contato direto da bactéria (e por conseguinte de seus produtos metabólicos) à superfície dental, e dificultando o acesso da saliva à mesma, impedindo assim a ação tamponante, que essa promove na presença do ácido láctico produzido por S. mutans (HAMADA et al, 1980). Esta capacidade de aderir à superfície dental pode ser aferida, de modo indireto in vitro, pela aderência promovida em superfícies abióticas, como placas de polipropileno (FRANCESCA et al, 2004).…”