Abstract
The mechanisms governing the epidemiology dynamics and success determinants of a specific healthcare-associated methicillin-resistant S. aureus (HA-MRSA) clone in hospital settings are still unclear. Important epidemiological changes have occurred in Europe since 2000 that have been related to the appearance of the ST22-IV clone. Between 2006 and 2010, we observed the establishment of the ST22-IV clone displacing the predominant Italian clone, ST228-I, in a large Italian university hospital. To investigate the factors associated with a successful spread of epidemic MRSA clones we studied the biofilm production, the competitive behavior in co-culture, the capacity of invasion of the A549 cells, and the susceptibility to infection in a murine model of acute pneumonia of the two major HA-MRSA clones, ST22-IV and ST228-I. We showed that persistence of ST22-IV is associated with its increased biofilm production and capacity to inhibit the growth of ST228-I in co-culture. Compared to ST228-I, ST22-IV had a significantly higher capacity to invade the A549 cells and a higher virulence in a murine model of acute lung infection causing severe inflammation and determining death in all the mice within 60 hours. On the contrary, ST228-I was associated with mice survival and clearance of the infection. ST22-IV, compared with ST228-I, caused a higher number of persistent, long lasting bacteremia. These data suggest that ST22-IV could have exploited its capacity to i) increase its biofilm production over time, ii) maintain its growth kinetics in the presence of a competitor and iii) be particularly invasive and virulent both in vitro and in vivo, to replace other well-established MRSA clones, becoming the predominant European clone.
Highlights
Infections caused by antibiotic-resistant strains of Staphylococcus aureus have risen to epidemic proportions globally [1]
Biofilm Production Selected methicillin-resistant S. aureus (MRSA) strains belonging to both epidemic (ST228-I, ST22-IV, ST8-IV) and sporadic (ST5-II, ST239-III, ST1-IV, ST8-IV USA300) clones were tested for their capacity to produce biofilm in vitro
Until the end of the 1990s, the international scenario was dominated by multidrug resistant (MDR) epidemic MRSA clones, suggesting a central role for multidrug resistance in the selection of successful MRSA clones, especially in the hospital environment where the selective antibiotic pressure is notoriously high
Summary
Infections caused by antibiotic-resistant strains of Staphylococcus aureus have risen to epidemic proportions globally [1]. Since 2003, MRSA has been isolated from livestock and humans exposed to infected animals in several countries, revealing the zoonotic potential of MRSA. Such MRSA has been dubbed livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) [5,6]. Interactions between these different reservoirs have been reported, including nosocomial infections by CA-MRSA [7,8] and LA-MRSA [9,10]
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