Research project

“Molecular epidemiology and pathogenesis mechanisms of methicillin-resistant Staphylococcus aureus: colonization, infection and nosocomial transmission, Argentina”

S. aureus is one of the more relevant human pathogens, both at the hospital and the community settings, due to its virulence and its great capacity of acquiring resistance to antibiotics (ATB), even though its natural reservoir is the human host, specifically in the nostrils. Thereby, exposure to S. aureus may go from colonization all the way up to fatal infection and this progression may be influenced by specific factors of the strain, the host or the transmission in the environment. Methicillin-resistant strains (MRSA), which are also resistant to all beta-lactam antibiotics (except anti-MRSA antibiotics), have become a main cause of hospital-associated infections (HA-MRSA) since the 60’s and currently, in many countries including Argentina, infection rates are higher than 50% leading to serious complications of antimicrobial therapy. In our country, this high infection rate was associated to the dissemination of an epidemic HA-MRSA clone, the Cordobes/Chilean (ST5-SCCmec I), which was identified in our laboratory.

In the beginning of the 90s’, MRSA started to have a main role in community-associated infections (CA-MRSA), which in some cases can lead to severe illness in previously healthy patients, without prior exposure to the hospital setting. CA-MRSA strains differ from HA-MRSA strains in various aspects, such as lack of multi-resistance to antibiotics, the presence of certain toxin coding genes (especially Panton Valentin Leukocydin, PVL) and small SCCmec (IV and V). Currently, these CA-MRSA strains are also responsible for hospital infections. This has a great impact on public health, if we consider that the hospitalized population is particularly vulnerable and that these strains are highly virulent, exhibit a high attack rate, are highly transmissible and possess the genetic potential to acquire multi-resistance to antibiotics. In this manner, CA-MRSA strains have a high potential to cause increased morbidity and mortality rates, which in turn is associated to a significant increase in health-related costs.

Through molecular surveys of S. aureus infections, we have identified epidemic MRSA clones disseminated both in the hospital setting (epidemic clone HA-MRSA Cordobes/Chilean, ST5-SCCmec I) as well as in the community setting (CA-MRSA PVL+, ST5-IV). This study was carried out first in Cordoba and then in the rest of the country in collaboration with the Instituto Carlos G. Malbran-INEI. In the current stage of this project, we aim to determine the molecular evolution of MRSA infections in our country as well as the effect of CA-MRSA strains compared with HA-MRSA and MSSA in colonization and hospital transmission. This way, we will evaluate colonization as a possible reservoir of this epidemic, analyzing the effect of CA-MRSA strains dissemination in the community as well as their transmission into the hospital setting. Our aim is to contribute to control MRSA dissemination both at the hospital and community settings, leading to decreased MRSA incidence infection rates, an improvement in our health standards and finally a reduction in hospital costs. Additionally, the characterization of the pathogenic features of local MRSA clones at the molecular level will be a valuable tool to design successful therapeutic strategies.