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Methicillin Resistant Staphylococcus aureus

S. aureus is the best characterized species among the Staphylococci, a genus of Gram-positive cocci comprising over 50 species and subspecies according to the NCBI Taxonomy browser.

 

S. aureus forms part of the normal staphylococcal flora of humans and various animal species.

 

In humans, S. aureus resides primarily in the anterior nares, where it shows a marked colonisation pattern: approximately 20-25% of individuals are persistent carriers (of mostly one strain), another 20% are non-carriers and the remaining proportion of the population (55-60%) carries S. aureus intermittently.Methicillin Resistant Staphylococcus aureus (MRSA)

 

In addition, S. aureus can frequently be found on other healthy skin sites, such as the axillae and the perineum. However, S. aureus is also the most important human pathogenic Staphylococcus species. The most common infections are minor skin infections that heal without medical intervention. However, severe infections can develop when S. aureus affects wounds or enters normally sterile body sites like blood (bacteraemia), the lungs (pneumonia) and the heart (endocarditis), and such infections frequently lead to death. This is very common in hospital settings, due to the ubiquitous presence of damaged skin sites.

 

In animals, besides being principally a colonizer of healthy skin sites, S. aureus is also one of the three major animal pathogenic Staphylococcus species, together with S. (pseud)intermedius and S. hyicus. The scale of infections Staphylococci are involved in is as broad as the number of animal species suffering from it, ranging from pneumonia, joint infections, osteomyelitis and septicaemia in poultry to subcutaneous abscesses, mastitis and pododermatitis in rabbits, dermatitis and cellulitis in horses and septicaemia in pigs. However, S. aureus plays its most significant animal pathogenic role as cause of intramammary infections in cattle and small ruminants.

 

Using biotyping methods, it was shown already several decades ago that S. aureus strains are host specific. In 1984 a biotyping system was proposed which could differentiate between man-, poultry-, sheep- and goats-, cattle- and non-host-specific strains of S. aureus. More recently, the use of modern genotyping methods has confirmed the host-specificity of S. aureus.

MRSA

 

An important impediment in the control of S. aureus infections, both in animals and humans, is the tendency of S. aureus to gain resistance to almost all classes of antimicrobial agents which it is subjected to. Probably the most important and striking example of this is its acquisition of resistance to β-lactam antibiotics. This is not only because of the rapidity with which resistance against these antibiotics developed recent years (see below), but also because of the major health care problem the resistant strains have subsequently become, in nosocomial settings as well as in the community, and both in human and veterinary medicine.

 

The first antibiotic ever used, penicillin, belongs to the meanwhile very comprehensive group of β-lactam antibiotics. These antimicrobial agents, characterized by the presence of a functionally essential β-lactam ring, bind to so called penicillin-binding proteins (PBPs), essential enzymes for bacterial cell wall construction and maintenance.

As a result of this binding, PBPs are inhibited, and lysis followed by cell death occurs.

 

However, soon after the first introduction of penicillin in the early 1940s, strains of S. aureus were identified that appeared to be resistant to its inhibiting activity. Later it became clear that this was caused by the production of penicillinases or β-lactamases.

 

Now, more than 90% of the human staphylococcal isolates produce penicillinases, regardless of clinical setting. Contrary, this type of resistance seldom exceeds 50% in strains from bovine mastitis and rabbit S. aureus seems to be very susceptible to all antibiotics, including β-lactams.

 

To counter the production of β-lactamases, β-lactamase-resistant β-lactam antibiotics were developed. The first agent in this class, the semi-synthetic methicillin, was introduced in clinical practice in 1959. However, similar to penicillin, shortly upon introduction the first methicillin-resistant staphylococci were detected and a few years later, the first infections involving methicillin-resistant Staphylococcus aureus (MRSA) were reported. Methicillin resistance was caused by the expression of an alternative penicillin-binding protein, called PBP2a or PBP2'. In contrast to the four native PBPs of S. aureus, PBP2a shows a very low affinity for β-lactam antibiotics, resulting in an enduring bacterial cell wall construction and, hence, survival of the bacterium.

 

PBP2a was found to be encoded by the mecA gene. This gene is localized in a mobile genetic element, named the Staphylococcal Cassette Chromosome mec (SCCmec), which is found integrated in the chromosome at a specific open reading frame (orf) of unknown function, orfX.

 

A SCCmec-element is composed of two essential gene complexes: the mec-complex and the ccr-complex. On the basis of their structural composition, mec- and ccr-complexes are categorized into different classes and types, respectively. Based on the class of mec-complex and the type of ccr-complex present, SCCmec-elements are then categorized into different SCCmec-types.

 

A distinctive feature of most MRSA is that the level of resistance can be influenced by environmental factors, conferring the expression of methicillin resistance an apparent inducibility. The cause of this is the heterogeneous nature of methicillin-resistance.

 

ROLE OF CODA-CERVA :

  • DIAGNOSIS

Isolation, characterisation (antibiotic resistance, virulence genes, PFGE, Spa-typing, MLST)

  • RESEARCH

Studies are ongoing investigating the epidemiology of MRSA in animals, host pathogen interaction in vitro and in vivo, and treatment by alternative means.

 

TEAM OF SCIENTISTS :

 

Vicky Jasson

Pierre Wattiau


CODA-CERVA PUBLICATIONS :

2011

- Hallin M, De Mendonça R, Denis O, Lefort A, El Garch F, Butaye P, Hermans K, Struelens MJ. Diversity of accessory genome of human and livestock-associated ST398 methicillin resistant Staphylococcus aureus strains. Infect Genet Evol. 2011 Mar;11(2):290-9.

2010

- Vanderhaeghen W, Cerpentier T, Adriaensen C, Vicca J, Hermans K, Butaye P. Methicillin-resistant Staphylococcus aureus (MRSA) ST398 associated with clinical and subclinical mastitis in Belgian cows. Vet Microbiol. 2010, 144(1-2):166-71

- Vanderhaeghen W, Hermans K, Haesebrouck F, Butaye P. Methicillin-resistant Staphylococcus aureus (MRSA) in food production animals. Epidemiol Infect. 2010,138(5):606-25.

2009

- Denis O., C. Suetens, M. Hallin, B. Catry, I. Ramboer, M. Dispas, G. Willems, B. Gordts, P. Butaye, and M.J. Struelens. 2009. Methicillin-resistant Staphylococcus aureus ST398 in swine farm personnel, Belgium. Emerg Infect Dis. 15:1098-1101.
- Persoons D., S. Van Hoorebeke, K. Hermans, P. Butaye, A. de Kruif, F. Haesebrouck, and J. Dewulf. 2009. Methicillin-resistant Staphylococcus aureus in poultry. Emerg Infect Dis. 15:452-453.
- Rasschaert G, W. Vanderhaeghen, I. Dewaele, N. Janez, X. Huijsdens, P. Butaye, and M. Heyndrickx. Comparison of fingerprinting methods for typing MRSA ST398. J Clin Microbiol. 2009 Aug 26. [Epub ahead of print]

2008

- Hermans, K., Lipinska, U., Denis, O., Deplano, A., Struelens, M.J., Nemati, M.; Pasmans, F., Butaye, P., Martens, A., Deprez, P., Haesebrouck, F. 2008. MRSA clone ST398-SCCmec IV as a cause of infections in an equine clinic. Vlaams Diergeneeskundig Tijdschrift, 77: 429-433.

2006

- Haesebrouck F., D. Vancraeynest, K. Hermans, B. Catry, P. Butaye, A. Decostere. 2006. Methicilline-resistente stapylococcus aureus stammen bij dieren: een gevaar voor de gezondheid van dier en mens? Vlaams Diergen. Tijdschr., 75, 254-261.