Smani's Lab


New therapeutic targets in the outer membrane of the bacteria associated with healthcare-related infections, through the study of host-pathogen interactions in vitro and in animal models.




Our group previously studied the host response to bacterial infections, deciphering the molecular and cellular mechanisms involved in host cell death caused by GNB such as Acinetobacter baumannii.  We have characterized for the first time a signaling pathway located in the membrane and cytosol of host cells, such as human lung epithelial cells, that regulates the adhesion and invasion of A. baumannii in host cells. We have identified the relationship between the phosphorylcholine (ChoP) present in the outer membrane of this pathogen, the platelet activating factor receptor (PAFR) present in the human lung epithelial cells, and the adherence and entry of A. baumannii in these host cells, as a mechanism for colonization and infection by A. baumannii.
Following this work, we have studied whether the outer membrane of A. baumannii harbors other adhesins involved in its adherence and invasion in the host. Three adhesins (OmpA, Omp33 and TonB) present in the outer membrane protein of A. baumannii were identified to bind to fibronectin, an extracellular matrix protein present in the host, which will allow the development of possible therapeutic approaches in the future to stop the entry of A. baumannii into the host and its escape from the immune system response.
Among these three adhesins, we have worked deeply with OmpA, characterizing its gene regulation and role in the pathogenesis of GNB, with the objective to develop and evaluate the therapeutic efficacy of OmpA inhibitors and their derivatives to inhibit the infections caused by OmpA expressing GNB. Moreover, we aimed to decipher how GNB respond to host signals, and which mechanisms used GNB to enter and persist inside host cells. To this end, we studied, using cellular and molecular techniques, the role of endosomes/lysosomes in the intracellular traffic of GNB, in particular A. baumannii. First data showed that the transcription factor EB (TFEB), well-known as inducer of the biogenesis of endosomes/lysosomes genes, participated in the entrance and persistence of A. baumannii inside human lung epithelial cells.

Selected publications on this topic



New antimicrobial resistance mechanisms.



We are also interested in deciphering new antimicrobial resistance mechanisms. We identified a new concept called ESRI (Extended Spectrum Resistance to β-lactams/β-lactamases inhibitors [BL/BLI]) in E. coli through the activation of TEM. Consequently we developed new systems to detect rapidly isolates of E. coli resistant to BL/BLI inhibitors and that develop ESRI such ESRI test (a colorimetric test) and MALDIpiptaz test (based to MALDI-TOF spectrum). Currently, we are validating these tests against a collection of clinical isolates of E. coli.


Selected publications on this topic


Non-antimicrobial approaches in the treatment of multidrug-resistant Gram-negative bacilli.

In 2016 we have registered the intellectual property of OmpA inhibitor, AOA-2, and its derivatives that showed therapeutic efficacy in monotherapy and in combination with antibiotics in murine model of infection by GNB such as
A. baumannii, Pseudomonas aeruginosa and E. coli [Ref.PCT/EP2015/072166]. This innovation was developed in collaboration with Dr. Ernest Giralt (Instituto de Investigación Biomédica, IRB de Barcelona). Thanks to the promising results, we co-founded DrugID Biotech to develop new anti-infectious agents. 
In the same way, we have evaluated another therapeutic approach based on the stimulation of the immune system by lysophosphatidylcholine. The obtained results, that showed preclinical efficacy in animal models, were registered as a patent [Ref. P201331715] and published, and opened the possibility of using lysophosphatidylcholine as an adjunctive antimicrobial treatment.
Similarly, we have demonstrated that tamoxifen, an anticancer agent that antagonize the oestrogen receptor, is able to modulate the immune response and to reduce the hyperinflammation in mice caused by the bacterial sepsis
On the other hand, we have assessed other therapeutic approaches based on repurposing drugs. Among them, we assessed the antibacterial effect of rafoxanide, oxyclozanide and niclosamide, anthelmintic drugs that showed synergy
with colistin in vitro and in animal models of infection  In addition, we assessed the antibacterial effect of tamoxifen metabolites against Gram-negative and Gram-positive bacteria.

Selected publications on this topic