Molybdenum nanoparticle coating to reduce MRSA contamination of public and healthcare environments

Staphylococcus aureus remains a leading cause of bacterial infections worldwide, ranging from skin and soft tissue infections to more severe conditions such as bacteremia, meningitis, pneumonia, osteomyelitis, and endocarditis. The high morbidity and mortality associated to S. aureus infections is due largely to its methicillin resistant form (MRSA), which was historically associated exclusively with hospitalacquired infections, but subsequently spread also to the community posing new threats and challenges. The burden caused by MRSA infections is currently widely recognized and its prevention and control have been identified as public health priorities in the European Union. However, the situation in Portugal remains troublesome: (i) the annual report of the European Antimicrobial Resistance Surveillance Network revealed that in 2013 Portugal continues to show a MRSA nosocomial prevalence (46.8%) that largely exceeds the European mean (18%) (1); (ii) a high incidence of MRSA was recently reported from the community (22%), as a result of dissemination from the hospital (2); (iii) the first European vancomycinresistant S. aureus (VRSA) was isolated in Portugal in 2013 (11). In addition, levels of MRSA in some Portuguese speaking African countries (PALOP) have reached 60%, representing further threat to Portugal due to the important demographic relationships (3, 4). Transmission of S. aureus, including MRSA, occurs mainly by direct humantohuman skin contact. Nevertheless, since MRSA can survive for long periods on inanimate objects, environmental surfaces constitute an important reservoir for dissemination as well. We have shown that MRSA of nosocomial origin contaminate massively handtouched surfaces in public buses in Lisbon (36%) and Oporto (26%) (5, 6). More alarming is the fact that 2% of the passengers had their hands contaminated with the same MRSA (5), evidencing that public transportation constitute an indubitable reservoir of MRSA and a transmission route from the hospital to the community. It is well known that environmental surfaces in the healthcare setting also represent a source of infection and colonization for patients and healthcare workers (HCW). Therefore, efficient measures to reduce MRSA environmental surfaces contamination are urgently needed in the healthcare system as well as in the community. Nanostructure materials deserve increasing attention in the biomedical field due to their antimicrobial activity in low concentrations. Nanoparticles of molybdenum, a nontoxic element, have recently showed efficacy in the laboratory against S. aureus (24, 25). The overall purpose of this project is to develop a molybdenum coating with biocidal activity against S. aureus to reduce contamination on environment surfaces, and therefore contribute to a local and global MRSA control. Our specific aims are the following: 1) Formulate molybdenum nanoparticle paints with biocidal activity against MRSA and with optimal adherence, applicability and durability when applied on different materials that mimic environmental surfaces; 2) Evaluate the effectiveness of molybdenum nanoparticle paints against MRSA, by testing its antimicrobial activity in the laboratory against known epidemic isolates and in two real world scenarios with accentuated MRSA contamination; 3) Determine if inanimate surfaces in PALOP hospitals act as S. aureus/ MRSA reservoirs, by determining for the first time its contamination rate by this pathogen; 4) Update the prevalence of S. aureus/ MRSA nasal colonization among patients and HCW in Angola and São Tomé and Príncipe; 5) Assess the current MRSA prevalence in public buses in Lisbon; 6) Determine the population structure of S. aureus strains currently circulating in public buses in Portugal and in hospitals in Angola and São Tomé, characterizing the isolates by a combination of molecular typing techniques; 7) Elucidate the role of environmental surfaces in S. aureus transmission in the hospital setting, by comparing the clonal types found among inanimate surfaces, patients and HCW; 8) Evaluate if surfaces coated with molybdenum paints may generate isolates resistant to molybdenum and determine the resistance genes involved; 9) Alert public authorities for the need of new public health strategies. These goals will be achieved by combining the internationally recognized knowhow of the research team at CENIMAT and IPS in the synthesis of composite nanoparticles and coatings production (7), with the irrefutable expertise of the PI and ITQB team on surveillance studies and molecular typing of S. aureus (810), and with the solid network of contacts of the PI and ESSCVP/CVP with PALOP hospitals. We expect this work will lead to the development of a promising and effective public health strategy to reduce the MRSA prevalence in Portugal and in PALOP nations, in both the community and clinical settings, and therefore take one step further in the universal fight against MRSA.