Virulence mechanisms of MRSA

Posted on September 12, 2012   by Daniel Amund, London Metropolitan University

The emergence of meticillin-resistant Staphylococcus aureus (MRSA) strains as potentially lethal pathogens is a continuing cause for public health concern worldwide. An understanding of the various virulence mechanisms used by these antibiotic-resistant bacterial pathogens is crucial to help prevent and treat the infections they cause.

 A review of MRSA virulence factors features in the September issue of the Journal of Medical Microbiology.

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S. aureus has the potential to cause a range of infections from minor skin conditions to life-threatening sepsis. Currently up to about 50% of S. aureus infections in Western Europe are due to MRSA strains. These strains are either healthcare-associated (HA-MRSA) or community-associated (CA-MRSA), though the distinction between the two may be blurred. HA-MRSA infections commonly present in chronically ill patients within hospitals, and are particularly invasive, such as pneumonia. CA-MRSA infections usually occur in healthy individuals, and usually present as skin and soft tissue infections.

MRSA possesses a number of weapons with which to cause infection – so-called virulence factors. One protein in particular is being widely studied; Panton Valentine Leukocidin (PVL) is a toxin which forms pores in leukocyte membranes, causing them to burst.  PVL is associated with abscess formation and severe necrotizing pneumonia. Most CA-MRSA strains possess PVL genes, though there is controversy on the role PVL plays in disease. Early studies suggested it was a major virulence factor in CA-MRSA though some recent data has suggested this is not the case. Other evidence shows presence of PVL does not influence the severity of HA-MRSA infections such as pneumonia.

The controversy over the role of PVL in MRSA virulence has focused research on other key protein players in the development of MRSA infection. Additional virulence factors include α-toxin, which also targets leukocytes, as well as platelets. Studies on α-toxin have revealed potential treatment options for MRSA infections, such as α-toxin-specific antibodies and blocking α-toxin receptors.

Other proteins being studied for their role in virulence are phenol soluble modulins (PSMs), which are produced by most staphylococci. They are released in high levels by CA-MRSA and are able to attack human neutrophils. Studies have shown that CA-MRSA strains with mutated versions of PSM genes are less able to cause infection. The ability of MRSA to colonize the human body has also been attributed to PSMs. Current studies looking at mobile genetic elements aim to understand what factors, in addition to PSMs, may give MRSA a competitive advantage for colonization.

Biofilm formation, especially on medical implants such as catheters, is another important virulence mechanism for MRSA. Bacterial cells in a biofilm show much greater resistance to antibiotics than free living cells; biofilms also help micro-organisms evade host immune responses. On-going studies are investigating different compounds and antibiotics which are effective against MRSA biofilms. Compounds shown to have anti-biofilm potential include manuka honey, quaternized chitosan, and the antiseptic povidone-iodine. Emerging technologies such as biomaterials that include nanosilver particles, which prevent MRSA biofilm formation, are also promising areas of research.

The review suggests that therapeutic agents targeted at specific virulence mechanisms of MRSA will have advantages over more broad-spectrum antibiotics as they will not affect beneficial bacteria, they will have fewer negative side effects and less potential for developing drug resistance. The use of vaccines appears to be a challenge, due to lack of effective protection observed in some studies, as well as safety concerns. Overall, a large amount of research is required in order to make significant breakthroughs in MRSA therapy although there are many promising areas under investigation.