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Antimicrobial Agents and Chemotherapy, October 2009, p. 4096-4102, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00484-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Impact of sarA on Daptomycin Susceptibility of Staphylococcus aureus Biofilms In Vivo {triangledown}

Elizabeth C. Weiss,1 Agnieszka Zielinska,1 Karen E. Beenken,1 Horace J. Spencer,2 Sonja J. Daily,1 and Mark S. Smeltzer1,3*

Department of Microbiology and Immunology,1 Department of Biostatistics,2 Department of Orthopaedic Surgery and Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722053

Received 13 April 2009/ Returned for modification 20 July 2009/ Accepted 25 July 2009

We used a murine model of catheter-associated biofilm formation to determine whether the mutation of the staphylococcal accessory regulator (sarA) has an impact on the susceptibility of established Staphylococcus aureus biofilms to treatment with daptomycin in vivo. The experiments were done with two clinical isolates, one of which (UAMS-1) was obtained from the bone of a patient suffering from osteomyelitis, while the other (UAMS-1625) is an isolate of the USA300 clonal lineage of community-acquired methicillin (meticillin)-resistant S. aureus. UAMS-1625 had a reduced capacity to form a biofilm in vivo compared to that of UAMS-1 (P = 0.0015), but in both cases the mutation of sarA limited biofilm formation compared to that of the corresponding parent strain (P ≤ 0.001). The mutation of sarA did not affect the daptomycin MIC for either strain, but it did result in increased susceptibility in vivo in the context of an established biofilm. Specifically, daptomycin treatment resulted in the clearance of detectable bacteria from <10% of the catheters colonized with the parent strains, while treatment with an equivalent daptomycin concentration resulted in the clearance of 46.4% of the catheters colonized with the UAMS-1 sarA mutant and 69.1% of the catheters colonized with the UAMS-1625 sarA mutant. In the absence of daptomycin treatment, mice with catheters colonized with the UAMS-1625 parent strain also developed skin lesions in the region adjacent to the implanted catheter. No such lesions were observed in any other experimental group, including untreated mice containing catheters colonized with the UAMS-1625 sarA mutant.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W. Markham, Mail Slot 511, Little Rock, AR 72205. Phone: (501) 686-7958. Fax: (501) 686-5359. E-mail: smeltzermarks{at}uams.edu

{triangledown} Published ahead of print on 3 August 2009.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4096-4102, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00484-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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