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Major families of multiresistant plasmids from geographically and epidemiologically diverse staphylococci.

ABSTRACT: Staphylococci are increasingly aggressive human pathogens suggesting that active evolution is spreading novel virulence and resistance phenotypes. Large staphylococcal plasmids commonly carry antibiotic resistances and virulence loci, but relatively few have been completely sequenced. We determined the plasmid content of 280 staphylococci isolated in diverse geographical regions from the 1940s to the 2000s and found that 79% of strains carried at least one large plasmid >20 kb and that 75% of these large plasmids were 20-30 kb. Using restriction fragment length polymorphism (RFLP) analysis, we grouped 43% of all large plasmids into three major families, showing remarkably conserved intercontinental spread of multiresistant staphylococcal plasmids over seven decades. In total, we sequenced 93 complete and 57 partial staphylococcal plasmids ranging in size from 1.3 kb to 64.9 kb, tripling the number of complete sequences for staphylococcal plasmids >20 kb in the NCBI RefSeq database. These plasmids typically carried multiple antimicrobial and metal resistances and virulence genes, transposases and recombinases. Remarkably, plasmids within each of the three main families were >98% identical, apart from insertions and deletions, despite being isolated from strains decades apart and on different continents. This suggests enormous selective pressure has optimized the content of certain plasmids despite their large size and complex organization.

SUBMITTER: Shearer JE

PROVIDER: S-EPMC3276174 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Major families of multiresistant plasmids from geographically and epidemiologically diverse staphylococci.

Shearer Julia E S JE Wireman Joy J Hostetler Jessica J Forberger Heather H Borman Jon J Gill John J Sanchez Susan S Mankin Alexander A Lamarre Jacqueline J Lindsay Jodi A JA Bayles Kenneth K Nicholson Ainsley A O'Brien Frances F Jensen Slade O SO Firth Neville N Skurray Ronald A RA Summers Anne O AO

G3 (Bethesda, Md.) 20111201 7

Staphylococci are increasingly aggressive human pathogens suggesting that active evolution is spreading novel virulence and resistance phenotypes. Large staphylococcal plasmids commonly carry antibiotic resistances and virulence loci, but relatively few have been completely sequenced. We determined the plasmid content of 280 staphylococci isolated in diverse geographical regions from the 1940s to the 2000s and found that 79% of strains carried at least one large plasmid >20 kb and that 75% of th ...[more]

PMID: 22384369

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Project description:UnlabelledAntimicrobial resistance in Staphylococcus aureus presents an increasing threat to human health. This resistance is often encoded on mobile plasmids, such as pSK41; however, the mechanism of transfer of these plasmids is not well understood. In this study, we first examine key protein-DNA interactions formed by the relaxase enzyme, NES, which initiates and terminates the transfer of the multidrug resistance plasmid pSK41. Two loops on the NES protein, hairpin loops 1 and 2, form extensive contacts with the DNA hairpin formed at the oriT region of pSK41, and here we establish that these contacts are essential for proper DNA cleavage and religation by the full 665-residue NES protein in vitro. Second, pSK156 and pCA347 are nonconjugative Staphylococcus aureus plasmids that contain sequences similar to the oriT region of pSK41 but differ in the sequence predicted to form a DNA hairpin. We show that pSK41-encoded NES is able to bind, cleave, and religate the oriT sequences of these nonconjugative plasmids in vitro. Although pSK41 could mobilize a coresident plasmid harboring its cognate oriT, it was unable to mobilize plasmids containing the pSK156 and pCA347 variant oriT mimics, suggesting that an accessory protein like that previously shown to confer specificity in the pWBG749 system may also be involved in transmission of plasmids containing a pSK41-like oriT. These data indicate that the conjugative relaxase in trans mechanism recently described for the pWBG749 family of plasmids also applies to the pSK41 family of plasmids, further heightening the potential significance of this mechanism in the horizontal transfer of staphylococcal plasmids.ImportanceUnderstanding the mechanism of antimicrobial resistance transfer in bacteria such as Staphylococcus aureus is an important step toward potentially slowing the spread of antimicrobial-resistant infections. This work establishes protein-DNA interactions essential for the transfer of the Staphylococcus aureus multiresistance plasmid pSK41 by its relaxase, NES. This enzyme also processed variant oriT-like sequences found on numerous plasmids previously considered nontransmissible, suggesting that in conjunction with an uncharacterized accessory protein, these plasmids may be transferred horizontally via a relaxase in trans mechanism. These findings have important implications for our understanding of staphylococcal resistance plasmid evolution.

Project description:The multidrug resistance gene cfr mediates resistance to multiple antimicrobial agents, including linezolid. Plasmids are the preferred vector for the dissemination of cfr. However, the presence and transmission of cfr-carrying plasmids among staphylococci from humans and animals have rarely been studied. Here, we investigated the presence of the cfr gene in 2,250 staphylococci of human clinical origin collected in Zhejiang, China, in 1998 to 2021 and in 3,329 porcine staphylococci preserved in our laboratories. The cfr gene was detected in 38 human isolates; its presence in Staphylococcus haemolyticus and Staphylococcus cohnii in 2003 was earlier than that identified in 2005, and Staphylococcus capitis (n = 30) was the predominant species. The cfr-carrying fragment in 38 isolates exhibited >99% nucleotide sequence similarity to plasmid pLRSA417 (39,504 bp), which was identified in 2015 and originated from a human clinical methicillin-resistant Staphylococcus aureus isolate from Zhejiang, China. The cfr-carrying plasmids in 18 MinION-sequenced staphylococci ranged in size from 32,697 bp to 43,457 bp. Fifteen plasmids were identical to pLRSA417, except for the inversion of an 8.4-kb segment comprising IS256-aacA/aphD-ISEnfa4_1-cfr-ISEnfa4_2, while the remaining 3 plasmids exhibited slightly different structures. Among the 114 cfr-positive staphylococci from pigs, pLRSA417-like plasmids were detected in 3 isolates. Intraspecies and interspecies conjugation occurred in human-derived pLRSA417-like plasmids. The presence of pLRSA417-like plasmids in staphylococci from multiple geographic regions and different hosts implied the possible transmission of the respective isolates between humans and animals. IMPORTANCE The therapeutic efficacy of the oxazolidinone antimicrobial linezolid is reduced by the emergence and dissemination of the multidrug resistance gene cfr. The cfr-carrying plasmid pLRSA417 was first identified in a clinical methicillin-resistant Staphylococcus aureus isolate, but its presence in staphylococci of human and animal origin has not been reported previously. This study showed that conjugative plasmids similar to pLRSA417 were detected mainly in Staphylococcus capitis and existed in different staphylococci in 2003 to 2021 in various clinical departments in the same hospital. pLRSA417-like plasmids were also present in staphylococci of food animal sources from different geographic regions, which suggested possible transmission among humans and animals.

Dataset Information

Major families of multiresistant plasmids from geographically and epidemiologically diverse staphylococci.

Publications

Major families of multiresistant plasmids from geographically and epidemiologically diverse staphylococci.

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