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Antimicrobial Agents and Chemotherapy, December 2006, p. 4070-4076, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00799-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A New Evolutionary Variant of the Streptogramin A Resistance Protein, Vga(A)LC, from Staphylococcus haemolyticus with Shifted Substrate Specificity towards Lincosamides{triangledown}

G. Novotna* and J. Janata

Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Received 3 July 2006/ Returned for modification 26 August 2006/ Accepted 21 September 2006

We found a new variant of the streptogramin A resistance gene, vga(A)LC, in clinical isolates of Staphylococcus haemolyticus resistant to lincomycin and clindamycin but susceptible to erythromycin and in which no relevant lincosamide resistance gene was detected. The gene vga(A)LC, differing from the gene vga(A) at the protein level by seven amino acid substitutions, was present exclusively in S. haemolyticus strains resistant to both lincosamides and streptogramin A (LSA phenotype). Antibiotic resistance profiles of the ATP-binding cassette (ABC) proteins Vga(A)LC and Vga(A) in the antibiotic-susceptible host S. aureus RN4220 were compared. It was shown that Vga(A)LC conferred resistance to both lincosamides and streptogramin A, while Vga(A) conferred significant resistance to streptogramin A only. Detailed analysis of the seven amino acid substitutions, distinguishing the two related ABC proteins with different substrate specificities, identified the substrate-recognizing site: four clustered substitutions (L212S, G219V, A220T, and G226S) in the spacer between the two ATP-binding cassettes altered the substrate specificity and constituted the lincosamide-streptogramin A resistance phenotype. A transport experiment with radiolabeled lincomycin demonstrated that the mechanism of lincosamide resistance in S. haemolyticus was identical to that of the reported macrolide-streptogramin B resistance conferred by Msr(A).

* Corresponding author. Mailing address: Institute of Microbiology AVCR, Videnska 1083, 14420 Prague, Czech Republic. Phone: 420 2 41 06 23 70. Fax: 420 2 41062347. E-mail: gnovotna{at}biomed.cas.cz.

{triangledown} Published ahead of print on 2 October 2006.

Antimicrobial Agents and Chemotherapy, December 2006, p. 4070-4076, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00799-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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