New Superbug Found in Cows and People
by Jocelyn Kaiser on 2 June 2011, 6:30 PM|
A novel form of deadly drug-resistant bacteria that hides from a standard test has turned up in Europe. Researchers found the so-called MRSA strain in both dairy cows and humans in the United Kingdom, suggesting that it might be passed from dairies to the general population. But before you toss your milk, don't panic: The superbug isn't a concern in pasteurized dairy products.
MRSA, short for methicillin-resistant Staphylococcus aureus, is a drug-resistant form of the widespread and normally harmless S. aureus bacteria. Many people walk around with MRSA in their noses or on their skin yet don't get sick. But in some hospital patients and people with weakened immune systems, MRSA thrives, and it is blamed for about 19,000 hospital deaths a year in the United States.
Mark Holmes of the University of Cambridge in the United Kingdom and colleagues stumbled upon the new strain while studying mastitis, or infected udders, in U.K. dairy cows. Some milk samples from sick cows contained S. aureus bacteria that grew in the presence of antibiotics, which is one test for MRSAs. Yet the same samples turned up negative for the drug-defying bacterium when the team used PCR, a DNA amplification technique, to detect a gene called mecA, which is found in all MRSA strains.
The PCR test doesn't always pick up variants of the gene it's meant to detect, however. To check this, the researchers sent a cow S. aureus sample to the Wellcome Trust Sanger Institute in Cambridge, which sequenced the bacterium's entire genome. "Lo and behold, there was a mecA gene there," one whose sequence overlapped with the better-known mecA by a surprisingly low 60%, Holmes said today in a press conference.
The researchers then looked for this mecA gene in people. They tested 74 samples of S. aureus isolated from people from the United Kingdom and Denmark that were drug resistant in the antibiotic growth test but not in the PCR test—most from carriers but some from patients who were sickened by MRSA. They found the new mecA in about two-thirds of the samples, they report today in The Lancet Infectious Diseases. A nearly identical mecA gene has also now been reported in human samples from Germany and Ireland.
The strain is still relatively rare—it probably makes up less than 1% of all detected MRSA cases, the U.K. team says. But its prevalence appears to have risen in the past decade. "More likely it's been around in the environment for a long time, and it's just getting into the human population," says University College Dublin microbiologist David Coleman, whose team reports on the Irish samples today in Antimicrobial Agents and Chemotherapy.
The new superbug probably isn't leading to missed infections, at least in the United Kingdom, because hospitals that suspect a patient is infected with an MRSA nearly always use the antibiotic growth test in addition to PCR, Holmes says. (Patients with a confirmed infection then receive antibiotics that work on MRSAs.) However, many hospitals in continental Europe are moving toward using only PCR tests; this is a warning that those tests need to be modified to test for the new mecA gene, Holmes says.
The study also points to dairy cows as a possible reservoir for the bug, just as pigs seem to pass MRSA to humans in the Netherlands. The bug probably doesn't get to humans through the milk supply, because almost all milk in the United Kingdom and Denmark is pasteurized, a process that kills bacteria. But workers who come into contact with infected dairy cows could be carriers. Holmes's team reports "circumstantial evidence" for this, such as the fact that genetic subtypes of the human and cow samples from the same geographical areas were nearly identical. "The main worry would be that these cows represent a pool of the bacteria" that farm workers spread into the human population, Holmes says.
The big mystery, says Patrick Schlievert of the University of Minnesota, Twin Cities, is where the unusual mecA gene came from. One possibility is that it originated long ago in a patient treated with multiple antibiotics and later somehow got into cows. "This should trigger an awful lot of research to figure out what is going on here," he says.
The Lancet Infectious Diseases, Early Online Publication, 3 June 2011
doi:10.1016/S1473-3099(11)70126-8Cite or Link Using DOI
Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study
Laura García-Álvarez PhD a, Matthew TG Holden PhD b, Heather Lindsay BSc a, Cerian R Webb PhD a, Derek FJ Brown PhD c, Martin D Curran PhD c, Enid Walpole FIMLS c, Karen Brooks BSc b, Derek J Pickard PhD b, Christopher Teale MRCVS d, Prof Julian Parkhill PhD b, Stephen D Bentley PhD b, Giles F Edwards FRCPath e, E Kirsty Girvan MSc e, Angela M Kearns PhD f, Bruno Pichon PhD f, Robert LR Hill PhD f, Anders Rhod Larsen PhD g, Robert L Skov MD g, Prof Sharon J Peacock PhD h, Prof Duncan J Maskell PhD a, Dr Mark A Holmes VetMB a
Animals can act as a reservoir and source for the emergence of novel meticillin-resistant Staphylococcus aureus (MRSA) clones in human beings. Here, we report the discovery of a strain of S aureus (LGA251) isolated from bulk milk that was phenotypically resistant to meticillin but tested negative for the mecA gene and a preliminary investigation of the extent to which such strains are present in bovine and human populations.
Isolates of bovine MRSA were obtained from the Veterinary Laboratories Agency in the UK, and isolates of human MRSA were obtained from diagnostic or reference laboratories (two in the UK and one in Denmark). From these collections, we searched for mecA PCR-negative bovine and human S aureus isolates showing phenotypic meticillin resistance. We used whole-genome sequencing to establish the genetic basis for the observed antibiotic resistance.
A divergent mecA homologue (mecALGA251) was discovered in the LGA251 genome located in a novel staphylococcal cassette chromosome mec element, designated type-XI SCCmec. The mecALGA251 was 70% identical to S aureus mecA homologues and was initially detected in 15 S aureus isolates from dairy cattle in England. These isolates were from three different multilocus sequence type lineages (CC130, CC705, and ST425); spa type t843 (associated with CC130) was identified in 60% of bovine isolates. When human mecA-negative MRSA isolates were tested, the mecALGA251 homologue was identified in 12 of 16 isolates from Scotland, 15 of 26 from England, and 24 of 32 from Denmark. As in cows, t843 was the most common spa type detected in human beings.
Although routine culture and antimicrobial susceptibility testing will identify S aureus isolates with this novel mecA homologue as meticillin resistant, present confirmatory methods will not identify them as MRSA. New diagnostic guidelines for the detection of MRSA should consider the inclusion of tests for mecALGA251.
Department for Environment, Food and Rural Affairs, Higher Education Funding Council for England, Isaac Newton Trust (University of Cambridge), and the Wellcome Trust.
a Department of Veterinary Medicine, University of Cambridge, UK
b The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
c Health Protection Agency, Addenbrooke's Hospital, Cambridge, UK
d Veterinary Laboratories Agency, Shrewsbury, UK
e Scottish MRSA Reference Laboratory, NHS Greater Glasgow and Clyde, Stobhill Hospital, Glasgow, UK
f Microbiology Services Division, Health Protection Agency, London, UK
g Department of Antimicrobial Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
h Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
Correspondence to: Dr Mark A Holmes, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK