Within-host diversity of MRSA antimicrobial resistances

Stanczak-Mrozek, Kinga I.; Manne, Anusha; Knight, Gwenan M.; Gould, Katherine A.; Witney, Adam A.; Lindsay, Jodi A.

doi:10.1093/jac/dkv119

Cited by 50 publications

(63 citation statements)

References 41 publications

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“…Other plasmids were not taken into account, and this could have provided more information. Furthermore, the use of data from other mobile genetic elements, such as bacteriophages, was not included in this study (36). In conclusion, our study strongly suggests that transmission of LA-MRSA in Dutch health care settings does occur.…”

Section: Discussionmentioning

confidence: 93%

“…However, no plasmids were found in other events, and in several cases, differences in plasmid composition were observed, although SNV and SCCmec analysis indicated that transmission was likely. Stanczak-Mrozek et al recently showed that MRSA variants that have acquired or lost mobile genetic elements were common in nasally colonized populations (36). Furthermore, a study using CC398 isolates showed that horizontal gene transfer, including plasmids, occurred at a very high frequency in vivo (26).…”

Section: Discussionmentioning

confidence: 99%

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Next-Generation Sequencing Confirms Presumed Nosocomial Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in the Netherlands

Bosch

Witteveen

Haenen

et al. 2016

Appl Environ Microbiol

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Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) was detected in 2003 and rapidly became the predominant MRSA clade in the Netherlands. Studies have shown that transmissions are difficult to identify, since this MRSA variant represents a genetically homogenous clade when current typing techniques are used. Here, next-generation sequencing was performed on 206 LA-MRSA isolates to assess the capability of LA-MRSA to be transmitted between humans. The usefulness of single nucleotide variants (SNVs), the composition of the SCCmec region, and the presence of plasmids to identify transmission of LA-MRSA were assessed. In total, 30 presumed putative nosocomial transmission events and 2 LA-MRSA outbreaks were studied; in most cases, SNV analysis revealed that the isolates of the index patient and the contact(s) clustered closely together. In three presumed events, the isolates did not cluster together, indicating that transmission was unlikely. The composition of the SCCmec region corroborated these findings. However, plasmid identification did not support our SNV analysis, since different plasmids were present in several cases where SNV and SCCmec analysis suggested that transmission was likely. Next-generation sequencing shows that transmission of LA-MRSA does occur in Dutch health care settings. Transmission was identified based on SNV analysis combined with epidemiological data and in the context of epidemiologically related and unrelated isolates. Analysis of the SCCmec region provided limited, albeit useful, information to corroborate conclusions on transmissions, but plasmid identification did not. IMPORTANCE In 2003, a variant of methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs was also found in pig farmers inFrance and the Netherlands. Soon thereafter, this livestock-associated MRSA (LA-MRSA) was identified in many other countries. Transmission of LA-MRSA between humans, particularly in the health care setting, is regarded to occur sporadically. Moreover, studies that describe LA-MRSA transmission used molecular characterization of isolates with limited discriminatory power, making the validity of the conclusion that transmission occurred questionable. In our study, we sequenced the complete genomes of 206 LA-MRSA isolates, obtained from more than 30 presumed LA-MRSA transmission events. Analysis of the data showed that transmission of LA-MRSA between humans had indeed occurred in more than 90% of these events. We conclude that transmission of LA-MRSA between humans does occur in Dutch health care settings; therefore, a decision to discontinue the search and destroy policy for LA-MRSA should be taken with caution. M ethicillin-resistant Staphylococcus aureus (MRSA) is an important cause of hospital-acquired and community-acquired infections (1). In 2003, an MRSA variant cultured from pigs and pig farmers emerged in the Netherlands and France (2, 3). This clonal lineage was designated MLST clonal complex 398 (CC398), and a large number of countries reported ...

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing Confirms Presumed Nosocomial Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in the Netherlands

Bosch

Witteveen

Haenen

et al. 2016

Appl Environ Microbiol

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“…More recently, the transducing ability of phages from serological groups A26 and L27 has been characterized and other accounts of transducing phages have been reported728, indicating that transduction capability is widespread among staphylococcal phages. The host range of staphylococcal phages is generally limited620, indicating that autotransduction is restricted to occur between closely related strains.…”

Section: Discussionmentioning

confidence: 99%

“…Nearly all strains carry phages stably integrated in the bacterial chromosome as prophages45 and extensive mobility of phages and other mobile genetic elements has been demonstrated between close relatives of S. aureus 6. The flexibility of a stable core genome and a large accessory mobile genome is believed to account for the extreme adaptability of S. aureus 457. For example, such flexibility allowed antibiotic-resistant clones of S. aureus to emerge and dominate in a hospital environment characterized by a high antibiotic selection pressure8 and in a controlled in vivo study transfer of mobile genetic elements between S. aureus strains was observed just 4 h after colonization of piglets9.…”

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confidence: 99%

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Bacterial viruses enable their host to acquire antibiotic resistance genes from neighbouring cells

et al. 2016

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Prophages are quiescent viruses located in the chromosomes of bacteria. In the human pathogen, Staphylococcus aureus, prophages are omnipresent and are believed to be responsible for the spread of some antibiotic resistance genes. Here we demonstrate that release of phages from a subpopulation of S. aureus cells enables the intact, prophage-containing population to acquire beneficial genes from competing, phage-susceptible strains present in the same environment. Phage infection kills competitor cells and bits of their DNA are occasionally captured in viral transducing particles. Return of such particles to the prophage-containing population can drive the transfer of genes encoding potentially useful traits such as antibiotic resistance. This process, which can be viewed as ‘auto-transduction', allows S. aureus to efficiently acquire antibiotic resistance both in vitro and in an in vivo virulence model (wax moth larvae) and enables it to proliferate under strong antibiotic selection pressure. Our results may help to explain the rapid exchange of antibiotic resistance genes observed in S. aureus.

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