soft cover Competing interests The authors declare that they have no competing
interests. Authors’ contributions RM carried out the adhesion assays, the enzymatic treatments and the isolation and identification of OppA protein and drafted the manuscript. CM participated in GAGs extraction and in the adhesion assays. SM carried out the clonage and purification of the OppA protein. ES and LQ conceived the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.”
“Background Immune-compromised patients are Nutlin-3a clinical trial at high risk of becoming infected by opportunistic fungi, such as Candida and Aspergillus sp. Candida sp. are the fourth most frequent cause of hospital acquired blood stream infections
and up to 90% of HIV patients receive mucosal candidiasis at least once . Although infections with non-albicans Candida sp. have emerged in recent years , the species C. albicans is still responsible for the Wortmannin majority of the cases [3, 4]. Several antifungals are available in the market, yet, toxicity and/or development of resistance represent major concerns . Among these is the former “gold standard” therapeutic amphotericin B that invariably causes toxicity in patients, negating the importance of its fungicidal activity. Although azoles and echinocandins represent the most widely used treatments of candidiasis, the acquisition of resistance can occur, leading to the risk of recurrent infections [6, 7]. Thus antifungals which impact new targets and have minimal side effects are urgently needed . In fungi, two-component signal transduction (TCST) systems have been implicated in osmotic Ergoloid and oxidative stress responses, cell-cycle control, red/far-red light responses, and virulence switches from non-pathogenic to pathogenic states [8–10]. Since TCST systems are absent in mammalian cells, they are attractive targets for the development
of new antifungals with probably minimal side effects in humans . Typical TCST systems in fungi include a histidine kinase (HK), a histidine phosphotransfer protein (HPT) and a response regulator protein (RR). The best understood fungal TCST system is part of the High Osmolarity Glycerol (HOG) pathway in S. cerevisiae. In the absence of osmotic stress, the transmembrane HK ScSln1p is active. This HK activity leads to phosphorylation of a histidine residue in the catalytic domain, the so-called HisKA domain, from which the phosphate group is transferred to an aspartic acid residue in an internal receiver domain (REC). Therefore, these HKs are called hybrid HKs. The phosphate group is then shuttled through the HPT protein Ypd1p to the PKC inhibitor terminal RR proteins Skn7p and Ssk1p [8, 11]. Phosphorylated Skn7p is a direct regulator of gene expression, whereas phosphorylated Ssk1p is not able to activate downstream targets.