Abstract
BackgroundA novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro. Bacterial biofilm has been considered a major virulence factor in central venous catheter-associated BSI. The mechanisms involved in biofilm formation/accumulation are multifactorial and complex. Studies have suggested that biofilm production was affected in vitro and vivo for agr-null mutants of S. aureus.ResultsThe impact of naturally occurring inhibition of agr signaling on virulence profiles and infections associated with the ST1 variant was investigated. agr dysfunction was detected in a significant percentage (13%) of the isolates with concomitant increase in biofilm accumulation in vitro and in vivo, and enhanced ability to adhere to and invade airway cells. The biofilm formed by these ST1 isolates was ica-independent and proteinaceous in nature. In fact, the improved colonization properties were paralleled by an increased expression of the biofilm-associated genes fnbA, spa and sasG. The transcription of sarA, a positive regulator of agr, was two-times reduced for the agr-dysfunctional MRSA. Remarkably, the agr inhibition was genetically stable. Indeed, agr-dysfunctional isolates succeed to colonize and cause both acute and chronic infections in hospitalized patients, and also to effectively accumulate biofilm in a mouse subcutaneous catheter implant model.ConclusionThe ability of agr-dysfunctional isolates to cause infections in humans and to form biofilm in the animal model suggests that therapeutic approaches based on agr-inactivation strategies are unlikely to be effective in controlling human-device infections caused by ST1 isolates. The increased biofilm accumulation associated with the acquisition of multiple antimicrobial resistant traits might have influenced (at least in part) the expansion of this USA400 related clone in our hospitals.
Highlights
A novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) lineage ST1- Staphylococcal cassette chromosome mec (SCCmec) IV was first reported in the 1980s among aborigines in Australia (WA-1 clone) and in the USA (MW2/USA400 clone) where cases of fatal infections were reported in Michigan, Minnesota and North Dakota [1,2,3]
Confocal laser scanning microscopy (CLSM) studies revealed that the agr-dysfunctional 08–008 accumulated a denser and compact biofilm when compared to the heterogeneous film formed by the agr-functional isolate (96/05)
Summary
A novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro. In 2005, a novel variant of the lineage ST1-SCCmecIV emerged in Rio de Janeiro city as an important cause of bloodstream infections (BSI) [12]. It is intriguing that despite the genetic relationship with Australian WA-1 and MW2/USA400, isolates of this novel clone were PVL-negative, multiresistant and mostly involved in hospital-associated BSI [12]. It is still poorly understood why isolates of CA-MRSA have become successful so quickly [13]. Extracellular DNA (eDNA) has been associated with bacterial biofilms [20]
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