Participation of membrane pumps (MDR) in the resistance of clinical strains of Stenotrophomonas maltophilia to antibiotics and chemotherapeutic agents

The aim of the planned research is to link the activity of the pump systems responsible for multidrug resistance (MDR) with the drug resistance profiles of clinical strains of Stenotrophomonas maltophilia and to search for new efflux systems present in this species. Currently, the main research on the pathogenicity of Gram-negative rods concerns strains of the Enterobacteriaceae family. However, the role of strains of other species in pathogenicity is also growing rapidly. Stenotophomonas maltophilia is one of the most frequently isolated Gram-negative rods responsible for nosocomial infections. It is an opportunistic pathogen, especially dangerous for patients with immunodeficiency, extensive burns, long-term hospitalization, and patients with cystic fibrosis. S. maltophilia strains cause many serious infections, including pneumonia, meningitis, and septicemia with a fatality rate of up to 69%, as in the case of bacteremia. S. maltophilia infections are a very serious therapeutic problem due to the widespread resistance of these strains to various types of antibiotics and chemotherapeutic agents. The presence of MDR (multi-drug resistance) pumps is one of the most important mechanisms of S. maltophilia resistance. MDR pumps are capable of removing various classes of antibiotics, chemotherapeutic agents, and disinfectants outside of the bacterial cells. In preliminary studies, the prevalence of ABC family efflux systems and some RND pumps among the tested S. maltophilia isolates was demonstrated. Taking into account the multiplicity of multi-drug resistance pump systems in the closely related species Pseudomonas aeruginosa, new multi-drug resistance systems should also be sought in S. maltophilia strains. The research will include a group of over 100 strains of S. maltophilia isolated from patients hospitalized in Warsaw hospitals. As part of the research, genes encoding pump systems from the RND family will be searched and the participation of selected systems in the resistance of strains will be determined using drug susceptibility tests and the real-time RT-qPCR method. Sequencing of genomic DNA of selected strains with atypical resistance phenotype will reveal new efflux systems present in S. maltophilia. Every year, an increasing number of S. maltophilia strains resistant to compounds used in the treatment of infections are observed. There is also an increasing number of immunocompromised people susceptible to S. maltophilia infections. These are very worrying phenomena that require a continuous improvement in knowledge of opportunistic pathogens, as well as genes and resistance mechanisms. So far, no studies have been conducted in Poland on MDR pumps occurring in clinical S. maltophilia isolates, global studies are fragmentary. In the presented project, they will be carried out for the first time, what is more, on such a large scale - they will cover all the MDR pump systems described so far from the RND and ABC families, and they will be performed with the participation of a large group of strains. The proposed research will enable an in-depth characterization of strains and will provide knowledge on the epidemiological situation and resistance of strains in Poland. They will also make it possible to compare the characteristics of Polish strains with strains isolated in various regions of the world. The performed genomic DNA sequencing of selected strains enabling the discovery of new efflux systems will expand the world knowledge about the resistance mechanisms of S. maltophilia strains. Moreover, the obtained data will broaden the knowledge useful in the treatment of S. maltophilia infections not only in Poland, but will also be an indication of the probability of the percentage of MDR system overexpression in drug resistance of strains of this bacilli in other regions of the world.