04 June 2014
By Janina Dordel
Phylogenetic tree of USA300 (black) and non-USA300 (grey) isolates. Colours in the outer ring show the isolate type, and colours in the middle circle indicate the neighborhoods. The lines connect isolates that emerged in the same household (coloured by neighbourhood) but are genetically very distant to each other.
Click for larger image.
Credit: doi: 10.1073/pnas.1401006111
Developments in whole genome sequencing and improvements in bioinformatics tools have been capitalised upon by scientists to provide unique insights in to the dynamics of evolution and spread of a wide range of pathogenic bacteria (see also ‘Battling against resistance
’ in this blog). In a recent study about community-associated MRSA in the USA, researchers needed even more data; they needed to learn about the patients’ home life and social life.
The bacteria Staphylococcus aureus, and in particular the antibiotic resistant ‘superbug’ Methicillin-resistant S. aureus (MRSA), has been the focus of recent studies. Its spread has been investigated on different geographical levels: from global to national down to hospital units and person-to-person transmission resulting in resolving an outbreak in a neo natal intensive care unit. However, most of these investigations focused on MRSA-types that are mainly found in hospitals. But of course there are also types that are not connected to the hospital setting but are found in the community.
These community-associated MRSA (CA-MRSA) strains only emerged in the late 1980s but have spread worldwide since then. In contrast, hospital-associated MRSA (HA-MRSA) strains have been around much longer, first appearing shortly after the introduction of the antibiotic methicillin in the 1960s. These strains cause disease in patients who are already ill, or at risk of infection from medical procedures. CA-MRSA represent a new and dangerous chapter in superbug story, as they often affect young and healthy people, and have the potential to cause severe skin and soft tissue infections.
The most successful strain of CA-MRSA of the last decade has been USA300, which spread throughout the United States of America and lead to an increase in cases of MRSA disease. However, its evolutionary history, the way it is spread, and the genetic basis for its success are only poorly understood.
In an attempt to shed light on some of these questions we used the genomes of 387 USA300 isolates from people in Northern Manhattan, New York, and added another 47 isolates originating from California and Texas for some broader context. Most exciting and unique for our dataset was the extra information we had for the New York isolates: the medical history, antibiotic treatment, social connections and the exact geographical location of the homes of the study participants. Furthermore, we did not only have isolates from healthy and infected people, but also isolates from household surfaces for some of the participants houses, representing bacteria that are a potential part of the transmission chain from person to person.
We compared the genomes of all isolates to each other and used single-base changes to reconstruct a genealogical tree. This tree revealed that the emergence of USA300 in Northern Manhattan was probably not caused by a single introduction followed by rapid spread but was more likely introduced several times. However, the tree also showed that isolates from the same household were genetically more similar to each other than isolates from different households.
This implies that households serve as critical reservoirs for USA300. This finding has great practical impact because, besides treating the infection of a person, the homes also have to be decolonised to prevent reinfection or the infection of other family members.
Another important finding was the resistance of 68 per cent of the isolates against the antibiotics of the fluoroquinolone family, which are commonly used in the US. After taking these antibiotics they are excreted onto the skin and expose its microbial flora (with S. aureus being one of them) to very low levels of the antibiotic. This can result in selection of mutations, which enable the surviving bacteria thrive in the presence of antibiotics and this may have promoted the spread of USA300. This once again demonstrates that we must be more aware and careful with our use of antibiotics.
Our study has shown that the combined use of whole-genome sequencing, novel bioinformatics tools and epidemiological data can help reveal the as yet unknown reservoirs, paths of transmission, and possible reasons for the success of USA300. Furthermore, it will also contribute to the analysis and understanding of other emerging pathogens in the community and long term help to control and erase them.
Janina Dordel is a Postdoctoral Fellow in the Pathogen Genomics group at the Wellcome Trust Sanger Institute.
- Uhlemann AC, et al (2014) Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proceedings of the National Academy of Sciences. doi: 10.1073/pnas.1401006111