It seems to be a freak of nature that in M. hominis, OppA has gained an additional ATPase NU7441 activity which raises the question as to its function. To date ecto-ATPase activity of OppA is unique to M. hominis among substrate-binding proteins of ABC-transporters of all three kingdoms. Thus it seems illogical that the ecto-ATPase is required for optimized peptide import. The findings of this study clearly demonstrate

that the OppA ecto-ATPase is essential for maximal cytoadhesion of M. hominis. In studying bacterial adhesion to polymer surfaces Stollenwerk and coworkers found that under conditions of starvation – by incubation in nutrient-poor buffer – the ATP content of adherent bacteria decreased after 24 h to 96 h whereas that of planktonic bacteria remained stable for up to 20 days [28]. This suggests that cytoadhesion is an energy-consuming process. Similar to our results presented here an ecto-ATPase-dependent cytoadherence has already been suggested

for Trypanosoma cruzi whose ATPase activity was strongly inhibited by using DIDS or suramin attended by a reduced adhesion to mouse resident macrophages [25]. Early work of Bredt and coworkers in the 1980′s demonstrated that cytoadhesion of the cell wall-less mollicutes is modulated by ATP. By monitoring the ATP content in the supernatant attachment of M. pneumoniae to glass surfaces was shown to depend on an intact energy metabolism [29]. In using a glucose-inhibitor, the ATP content declined and attachment was abrogated. In using cAMP inhibitor an ATPase inhibitor, ATP content accumulates leading

https://www.selleckchem.com/products/pi3k-hdac-inhibitor-i.html to a decreased cytoadherence. Bredt and coworkers hypothesized that the first step of colonization is energy dependent either to energize the CP-690550 solubility dmso membrane thus increasing some binding sites on the surface, or to modulate the contractile cytoskeleton [29]. The free energy of ATP hydrolysis by P-loop NTPases is typically utilized to introduce conformational changes in other molecules [30]. As adhesion of mycoplasmal cytoadhesins does not depend on ATP-hydrolysis at all, as demonstrated in this study for the P60/P80 membrane complex of M. hominis, ATPase dependent adhesion of OppA is predicted to play a special role in M. hominis. In 2008 OppA was shown to mediate apoptosis, to induce ATP-efflux and a concomitant ATP-depletion of the M. hominis-colonized host cell [15]. This is in accordance to the recent findings that the cytoadherence of M. pneumoniae induces an ATP-efflux from the colonized host [31]. ATP- efflux was considered as a stress-associated danger signal as it stimulates P2X7-receptors of the host leading to the expression of pro-inflammatory cytokines. It is well known that extracellular ATP signals through P2 receptors to modulate the immune and inflammatory response in a variety of host cells, including immune and non-immune cells, sometimes leading to apoptosis or necrosis of the cells [32].