Sequence of a staphylococcal gene, vat, encoding an acetyltransferase inactivating the A-type compounds of virginiamycin-like antibiotics

Allignet, Jeanine; Loncle, V.; Simenel, Catherine; Delepierre, Murielle; Solh, Névine El

doi:10.1016/0378-1119(93)90350-c

Cited by 102 publications

(60 citation statements)

References 22 publications

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“…The following PCR primers were used for the detection of streptogramin resistance genes: the acetyltransferase gene vatA was amplified with primers vatA1 (5Ј-CAA TGA CCA TGG ACC TGA TC) and vatA2 (5Ј-AGC ATT TCG ATA TCT CC), vatB was amplified with primers vatB1 (5Ј-CCT GAT CCA AAT AGC ATA TAT CC) and vatB2 (5Ј-CTA AAT CAG AGC TAC AAA GTG), and vatC was amplified with primers vatC1 (5Ј-TGG CAA AAT CAG CAA GG) and vatC2 (5Ј-TCG TCT CTA TCT CTA GGT CC), the genes encoding efflux pumps vgaA were amplified with primers vgaA1 (5Ј-AGT GGT GGT GAA GTA ACA CG) and vgaA2 (5Ј-CTT GTC TCC TCC GCG AAT AC), and those encoding vgaB were amplified with primers vgaB1 (5Ј-TCT CTC AAT TAG AAG AAC C) and vgaB2 (5Ј-TTA TCT ATT CGT GTT TCC) (except for the primers for vgaB [3,4,6]). The streptogramin B resistance determinants vgbA and vgbB were amplified using primers vgbA1 (5Ј-CCA GAT TCA GCA CCC TAC G) and vgbA2 (5Ј-CCC CCC ATT CAG TAA ACC), as well as vgbB1 (5Ј-CAG CAG TCT AGA TCA GAG TGG) and vgbB2 (5Ј-CAT ACG GAT CCA TCT TTT CC) (1,6).…”

Section: Bacterial Isolatesmentioning

confidence: 99%

“…Two kinds of mechanisms are known to mediate resistance to the A compound: inactivation of the drug by acetylation and efflux. In staphylococci, three acetyltransferase genes, vatA, vatB, and vatC (3,4,6) and two genes for efflux pumps (ABC porters), vgaA and vgaB (2, 5), have been described. These streptogramin A and B resistance genes are often located on the same plasmids (6).…”

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Methicillin-Resistant, Quinupristin-Dalfopristin-Resistant Staphylococcus aureus with Reduced Sensitivity to Glycopeptides

et al. 2001

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Of 3,052 Staphylococcus aureus strains collected by the European SENTRY surveillance study, 35 were found to be nonsusceptible to quinupristin-dalfopristin (MIC of >2 mg/liter). These isolates originated from four hospitals in France and one in Spain. In isolates from two Parisian hospitals exhibiting the same SmaI macrorestriction pattern, streptogramin resistance was based on vatA and vgbA. One isolate from a hospital in Lyon and 22 from a hospital in Lille were of the vatB vgaB streptogramin A resistance genotype and possessed ermA and/or ermC. As deduced from the loss of either streptogramin A or streptogramin B resistance determinants in particular isolates, resistance to quinupristin-dalfopristin requires mechanisms conferring resistance to both compounds. The SmaI macrorestriction patterns of strains from hospitals in Lille and Lyon were different; however, similarity analysis suggested a relatedness of 20 methicillin-resistant S. aureus strains from the Lille hospital, a finding confirmed by PCR typing based on three different genomic polymorphisms. These groups of isolates were found to be hetero-glycopeptide-intermediate susceptible S. aureus. Information about the failure of glycopeptide chemotherapy has not been available.Methicillin-resistant Staphylococcus aureus (MRSA) has become an important nosocomial pathogen in many countries. Glycopeptides have been the drugs of choice for treating MRSA infections. However, with the emergence of intermediate susceptibility to glycopeptides, first reported from sporadic cases in many countries (12, 20) and more recently also from an outbreak of infections (11), other treatment alternatives such as quinupristin-dalfopristin and linezolid have become important. Quinupristin-dalfopristin is a combination of streptogramin B and A compounds with a synergistic activity against most gram-positive bacteria (8,14).Resistance to the B component is mediated by methylation of 23S rRNA which confers macrolide-lincosamide-streptogramin B (MLS B ) resistance when the erm genes are expressed constitutively (7). A second mechanism is hydrolysis of the drug by a lactonase encoded by the vgbA and the vgbB genes, respectively (1, 6). Two kinds of mechanisms are known to mediate resistance to the A compound: inactivation of the drug by acetylation and efflux. In staphylococci, three acetyltransferase genes, vatA, vatB, and vatC (3, 4, 6) and two genes for efflux pumps (ABC porters), vgaA and vgaB (2, 5), have been described. These streptogramin A and B resistance genes are often located on the same plasmids (6).In this study we describe quinupristin-dalfopristin-resistant S. aureus strains collected during the course of the European SENTRY surveillance study in European countries (18). These strains were characterized in our laboratory with regard to streptogramin resistance genes, phenotypic resistance to other antibiotics, and genotype. MATERIALS AND METHODS Bacterial isolates.A total of 35 isolates of S. aureus exhibiting insensitivity to quinupristin-dalfopristin originated f...

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Section: Bacterial Isolatesmentioning

confidence: 99%

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confidence: 99%

Methicillin-Resistant, Quinupristin-Dalfopristin-Resistant Staphylococcus aureus with Reduced Sensitivity to Glycopeptides

et al. 2001

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“…Resistance to A compounds may be conferred by two categories of genes: (i) vatABCDE (4,5,8,18,25,35), encoding related acetyltransferases that inactivate the drug and are found on staphylococcal and/or Enterococcus faecium plasmids, and (ii) vgaAB (2, 6) and lsa (28), encoding related ATP-binding proteins, the resistance mechanism of which has not been elucidated. vga-type genes are found in staphylococcal plasmids but not in E. faecium strains, whereas lsa…”

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confidence: 99%

Clonal Diversity among Streptogramin A-Resistant Staphylococcus aureus Isolates Collected in French Hospitals

Haroche¹,

Morvan²,

Davi³

et al. 2003

J Clin Microbiol

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We analyzed 62 clinical isolates of streptogramin A-resistant (SGA r ) Staphylococcus aureus collected between 1981 and 2001 in 14 hospitals located in seven French cities. These isolates, including five with decreased susceptibility to glycopeptides, were distributed into 45 antibiotypes and 38 SmaI genotypes. Each of these genotypes included between 1 and 11 isolates, the SmaI patterns of which differed by no more than three bands. Although numerous clones were identified, we observed the spread of monoclonal isolates either within the same hospital or within hospitals in distinct cities and at large time intervals. Hybridization with probes directed against 10 SGA r genes (vatA, vatB, vatC, vatD, vatE, vgaA, vgaB, vgaAv, vgbA, and vgbB) revealed six patterns: vgaAv (21 isolates), vatA-vgbA (24 isolates), vgaAv-vatB-vgaB (14 isolates), vgaAv-vatA-vgbA (1 isolate), vgaAv-vatA-vgbA-vatB-vgaB (1 isolate), and vgaA (1 isolate). We detected at least one SGA r determinant in all of the tested isolates. vgaAv, which is part of the recently characterized transposon Tn5406, was found in 59.7% of the tested isolates. Of the 16 streptogramin B-susceptible isolates, 14 carried vgaAv alone and were susceptible to the mixtures of streptogramins, whereas the 2 isolates carrying vgaAv-vatB-vgaB were resistant to these mixtures. vatA-vgbA was found on plasmids of the same apparent size in 26 (42%) of the tested clinical isolates from 18 unrelated SmaI genotypes. The possible dissemination of some of the multiple clones characterized in the present study with an expected increased selective pressure of streptogramins following the recent licensing of Synercid (quinupristin-dalfopristin) must be carefully monitored.Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen worldwide. Glycopeptides have been the reference drugs for the treatment of MRSA infections (16,21,30). After the emergence of clones with decreased susceptibility to these antibiotics, first reported as sporadic cases in several countries and more recently also as outbreaks, alternative treatments such as quinupristin-dalfopristin (Synercid) have been promoted (17,21,33). Quinupristin and dalfopristin are derivatives of pristinamycins IA and IIA, respectively (10). Quinupristin-dalfopristin is an injectable, semisynthetic, mixture with a synergistic activity against most gram-positive pathogens. Since 1999, quinupristin-dalfopristin has been available for use in hospitals for the treatment of infections caused by gram-positive cocci that are resistant to other antibiotics.Quinupristin-dalfopristin and the natural antibiotics produced by streptomycetes, such as streptogramin, pristinamycin, synergistin, mikamycin, and virginiamycin, are mixtures of two classes of compounds, A and B, with distinct primary structures (10, 14). The A compounds are polyunsaturated cyclic macrolactones, and the B compounds are cyclic hexadepsipeptides. Both types of compounds bind different targets in the peptidyltransferase domain of the 23S ribosoma...

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“…Amino acid substitutions in vital regions of the enzyme-DNA complex commonly referred as the quinolone resistance-determining region (QRDR) reduces affinity of quinolones for both of its targets [62]. The reduced susceptibility of MRSA to the QuinupristinDulfopristin (QD) combination is due to genes coding for acetyltransferases vatA, vatB and vatC [63].…”

Section: Dna Damage or Mutationmentioning

confidence: 99%

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

Saxena

Gomber

2010

Open Medicine

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AbstractStaphylococcus aureus is the third most dreaded pathogen posing a severe threat due to its refractory behavior against the current armamentarium of antimicrobial drugs. This is attributed to the evolution of an array of resistance mechanisms responsible for morbidity and mortality globally. Local and international travel has resulted in the movement of drug resistant S. aureus clones from hospitals into communities and further into different geographical areas where they have been responsible for epidemic outbreaks. Thus, there is a dire necessity to refrain further cross movement of these multidrug resistant clones across the globe. The plausible alternative to prevent this situation is by thorough implementation of regulatory aspects of sanitation, formulary usage and development of new therapeutic interventions. Various strategies like exploring novel antibacterial targets, high throughput screening of microbes, combinatorial and synthetic chemistry, combinatorial biosynthesis and vaccine development are being extensively sought to overcome multidrug resistant chronic Staphylococcal infections. The majority of the antibacterial drugs are of microbial origin and are prone to being resisted. Anti-staphylococcal plant natural products that may provide a new alternative to overcome the refractory S.aureus under clinical settings have grossly been unnoticed. The present communication highlights the new chemical entities and therapeutic modalities that are entering the pharmaceutical market or are in the late stages of clinical evaluation to overcome multidrug resistant Staphylococcal infections. The review also explores the possibility of immunity and enzyme-based interventions as new therapeutic modalities and highlights the regulatory concerns on the prescription, usage and formulary development in the developed and developing world to keep the new chemical entities and therapeutic modalities viable to overcome antimicrobial resistance in S. aureus.

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Sequence of a staphylococcal gene, vat, encoding an acetyltransferase inactivating the A-type compounds of virginiamycin-like antibiotics

Cited by 102 publications

References 22 publications

Methicillin-Resistant, Quinupristin-Dalfopristin-Resistant Staphylococcus aureus with Reduced Sensitivity to Glycopeptides

Methicillin-Resistant, Quinupristin-Dalfopristin-Resistant Staphylococcus aureus with Reduced Sensitivity to Glycopeptides

Clonal Diversity among Streptogramin A-Resistant Staphylococcus aureus Isolates Collected in French Hospitals

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

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