Two paediatric cases of skin and soft-tissue infections due to clindamycin-resistant Staphylococcus aureus carrying a plasmid-encoded vga(A) allelic variant for a putative efflux pump

Qin, Xuan; Poon, Brian; Kwong, Justin; Niles, Denver T.; Schmidt, Byron Z.; Rajagopal, Lakshmi; Gantt, Soren

doi:10.1016/j.ijantimicag.2011.03.007

Cited by 13 publications

(10 citation statements)

References 9 publications

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“…We did not observe any correlation between erm variant and inducibility of clindamycin resistance. We did not find vga (A) LC in any of the isolates (21). …”

Section: Resultscontrasting

confidence: 55%

Prediction of Staphylococcus aureus Antimicrobial Resistance by Whole-Genome Sequencing

et al. 2014

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Whole-genome sequencing (WGS) could potentially provide a single platform for extracting all the information required to predict an organism's phenotype. However, its ability to provide accurate predictions has not yet been demonstrated in large independent studies of specific organisms. In this study, we aimed to develop a genotypic prediction method for antimicrobial susceptibilities. The whole genomes of 501 unrelated Staphylococcus aureus isolates were sequenced, and the assembled genomes were interrogated using BLASTn for a panel of known resistance determinants (chromosomal mutations and genes carried on plasmids). Results were compared with phenotypic susceptibility testing for 12 commonly used antimicrobial agents (penicillin, methicillin, erythromycin, clindamycin, tetracycline, ciprofloxacin, vancomycin, trimethoprim, gentamicin, fusidic acid, rifampin, and mupirocin) performed by the routine clinical laboratory. We investigated discrepancies by repeat susceptibility testing and manual inspection of the sequences and used this information to optimize the resistance determinant panel and BLASTn algorithm. We then tested performance of the optimized tool in an independent validation set of 491 unrelated isolates, with phenotypic results obtained in duplicate by automated broth dilution (BD Phoenix) and disc diffusion. In the validation set, the overall sensitivity and specificity of the genomic prediction method were 0.97 (95% confidence interval [95% CI], 0.95 to 0.98) and 0.99 (95% CI, 0.99 to 1), respectively, compared to standard susceptibility testing methods. The very major error rate was 0.5%, and the major error rate was 0.7%. WGS was as sensitive and specific as routine antimicrobial susceptibility testing methods. WGS is a promising alternative to culture methods for resistance prediction in S. aureus and ultimately other major bacterial pathogens.

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“…We did not observe any correlation between erm variant and inducibility of clindamycin resistance. We did not find vga (A) LC in any of the isolates (21). …”

Section: Resultscontrasting

confidence: 55%

Prediction of Staphylococcus aureus Antimicrobial Resistance by Whole-Genome Sequencing

et al. 2014

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“…This evolutionary variant of vga (A) encodes for an ABC transporter and has been reported in Staphylococcus resistant to lincosamides and streptogramin (Novotna and Janata ; Qin et al . ). Failure to observe clindamycin resistance in some of our vga (A) LC ‐positive isolates can be explained by the different phenotypic methods used to determine clindamycin resistance because we used a broth microdilution method whereas agar dilution or disc diffusion was applied in previous studies.…”

Section: Discussionmentioning

confidence: 97%

Multidrug-resistant coagulase-negative Staphylococci in food animals

Bhargava

Zhang

2012

J Appl Microbiol

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Aims To study the antimicrobial resistance of coagulase‐negative staphylococci (CoNS) in animals. Methods and Results In the present study, a total of 87 CoNS recovered from food animals were characterized by antimicrobial susceptibility testing, resistance gene identification and conjugation. Of the seven species studied, Staphylococcus lentus, Staphylococcus sciuri, Staphylococcus xylosus and Staphylococcus haemolyticus accounted for over 96% of the isolates. In addition to β‐lactam resistance (100%), high percentages of CoNS were resistant to tetracycline (67·8%), erythromycin (36·7%), clindamycin (27·5%) and quinopristin/dalfopristin (14·9%). Importantly, 47 (54%) isolates were resistant to at least three antimicrobial classes, including six CoNS resistant to six antimicrobial classes. The common genes for the above‐mentioned resistance phenotypes were mec(A), tet(M), erm(A) and vga(A)LC, which were identified from 68·7%, 61%, 56·2% and 69·2% of the isolates, respectively. tet(M) was conjugatively transferable from 10 tetracycline‐resistant CoNS to a Enterococcus strain, underlining the potential of antimicrobial resistance transfer from Staphylococcus to the commensal bacteria in human. Conclusions Multidrug resistance and resistance to non‐β‐lactam antimicrobials are common in CoNS in animals. Significance and Impact of the Study The data improve our understanding on the extent to which CoNS contribute to the dissemination of antimicrobial resistance in the food production environment.

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“…Since the first report of Vga(A) as a streptogramin A (SgA) resistance determinant (5), several variants differing in their ability to confer resistance to SgA, lincosamides (L), and/or pleuromutilins (P) were reported ( Fig. 1) (4,(6)(7)(8)(9)(10)(11). For clarity in this paper, we refer to unspecified Vga(A) variants as Vga(A)*, use Vga(A) only for the originally described Vga(A) protein (NCBI protein database accession number AAA26684) conferring resistance to SgA (5), and use Vga(A) LC (the LC subscript indicates resistance to lincomycin and clindamycin) for the variant with NCBI protein database accession number ABH10964 that confers resistance to both L and SgA (4).…”

mentioning

confidence: 99%

Detailed Mutational Analysis of Vga(A) Interdomain Linker: Implication for Antibiotic Resistance Specificity and Mechanism

Lenart

Vimberg

Veselá

et al. 2015

Antimicrob Agents Chemother

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Detailed mutational analysis examines the roles of individual residues of the Vga(A) linker in determining the antibiotic resistance phenotype. It defines a narrowed region of residues 212 to 220 whose composition determines the resistance specificity to lincosamides, pleuromutilins, and/or streptogramins A. From the analogy with the recently described function of the homologous ABC-F protein EttA as a translational factor, we infer that the Vga(A) linker interacts with the ribosome and directly or indirectly affects the binding of the respective antibiotic.T he ABC-F family of ABC transporters comprises soluble proteins with two nucleotide binding domains (NBD) (Pfam accession number PF00005) separated by a flexible linker of approximately 80 amino acid residues. In contrast to typical ABC transporters, ABC-F proteins do not have any transmembrane domain. They usually participate in nontransport cellular functions, including translation regulation and DNA excision, and are also involved in antibiotic resistance. Antibiotic resistance ABC-F proteins are collectively referred to as ARE (antibiotic resistance) proteins (1). The mechanism of resistance conferred by ARE proteins is not well understood.Vga(A) is one of the most-studied ARE proteins (2-4). Since the first report of Vga(A) as a streptogramin A (SgA) resistance determinant (5), several variants differing in their ability to confer resistance to SgA, lincosamides (L), and/or pleuromutilins (P) were reported ( Fig. 1) (4, 6-11). For clarity in this paper, we refer to unspecified Vga(A) variants as Vga(A)*, use Vga(A) only for the originally described Vga(A) protein (NCBI protein database accession number AAA26684) conferring resistance to SgA (5), and use Vga(A) LC (the LC subscript indicates resistance to lincomycin and clindamycin) for the variant with NCBI protein database accession number ABH10964 that confers resistance to both L and SgA (4).Comparison of the Vga(A) and Vga(A) LC proteins showed that the shift in resistance between SgA and L is determined by amino acid substitutions L212S, G219V, A220T, and G226S clustered in a sequence only 15 amino acids long within the interdomain linker, which is the main source of polymorphism for all Vga(A)* proteins ( Fig. 1) (4). Nothing is known about how these individual variable residues contribute to antibiotic specificity. We set out to decipher the relationship between the linker variability of Vga(A)* variants and the resistance phenotype using detailed mutational study of the Vga(A) and Vga(A) LC linkers. Implications of our results for the proposed resistance mechanism are discussed.We have mutated amino acid residues of the linker in positions 212, 219, 220, and 226 to create a set of mutant forms of Vga(A)* that contain all but one of the possible combinations of Vga(A)-and Vga(A) LC -specific residues in their respective positions. Sitedirected mutagenesis was performed using two complementary primers according to the QuikChange site-directed mutagenesis kit protocol (Stratagene). The construct pB...

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Two paediatric cases of skin and soft-tissue infections due to clindamycin-resistant Staphylococcus aureus carrying a plasmid-encoded vga(A) allelic variant for a putative efflux pump

Cited by 13 publications

References 9 publications

Prediction of Staphylococcus aureus Antimicrobial Resistance by Whole-Genome Sequencing

Prediction of Staphylococcus aureus Antimicrobial Resistance by Whole-Genome Sequencing

Multidrug-resistant coagulase-negative Staphylococci in food animals

Detailed Mutational Analysis of Vga(A) Interdomain Linker: Implication for Antibiotic Resistance Specificity and Mechanism

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