Beatson Lab

Microbial Genomics

Category: Uncategorized

Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone


Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three m6A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for m6A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located.

Forde BM, Phan MD, Gawthorne JA, Ashcroft MM, Stanton-Cook M, Sarkar S, Peters KM, Chan KG, Chong TM, Yin WF, Upton M, Schembri MA, Beatson SA

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Transfer of scarlet fever-associated elements into the group A Streptococcus M1T1 clone


The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone, with bacteriophage-encoded determinants DNase Sda1 and superantigen SpeA2 contributing to enhanced virulence and colonization respectively. Outbreaks of scarlet fever in Hong Kong and China in 2011, caused primarily by emm12 GAS, led to our investigation of the next most common cause of scarlet fever, emm1 GAS. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 scarlet fever clones in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements.

Ben Zakour NL, Davies MR, You Y, Chen JH, Forde BM, Stanton-Cook M, Yang R, Cui Y, Barnett TC, Venturini C, Ong CL, Tse H, Dougan G, Zhang J, Yuen KY, Beatson SA, Walker MJ

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Hospital-Wide Eradication of a Nosocomial Legionella pneumophila Serogroup 1 Outbreak

Background. Two proven nosocomial cases of Legionella pneumonia occurred at the Wesley Hospital (Brisbane, Australia) in May 2013. To trace the epidemiology of these cases, whole genome sequence analysis was performed on Legionella pneumophila isolates from the infected patients, prospective isolates collected from the hospital water distribution system (WDS), and retrospective patient isolates available from the Wesley Hospital and other local hospitals.

Results. The 2011 and 2013 L. pneumophila patient isolates were serogroup 1 and closely related to all 2013 hospital water isolates based on single nucleotide polymorphisms and mobile genetic element profiles, suggesting a single L. pneumophila population as the source of nosocomial infection. The L. pneumophila population has evolved to comprise 3 clonal variants, each associated with different parts of the hospital WDS.

Conclusions. This study provides an exemplar for the use of clinical and genomic epidemiological methods together with a program of rapid, effective remedial biofilm, plumbing and water treatment to characterize and eliminate a L. pneumophila population responsible for nosocomial infections.

Bartley PB, Ben Zakour NL, Stanton-Cook M, Muguli R, Prado L, Garnys V, Taylor K, Barnett TC, Pinna G, Robson J, Paterson DL, Walker MJ, Schembri MA, Beatson SA. Clin Infect Dis. 2015 Oct 13. pii: civ870.

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Global Dissemination of a multidrug resistant Escherichia coli clone

What is the study about?

We examined the DNA of a particular type of multidrug resistant E. coli called ST131. This type of bacteria was relatively unheard of until about 5 years ago but is now one of the most common causes of urinary tract and bloodstream infections. We were able to track the global emergence of ST131 by analysing a collection of isolates from all over the world. We found that they all evolved from a common ancestor quite recently and were resistant to multiple antibiotics.

Why is it important?

Urinary tract infections affect more than 150 million people around the world every year and about 50% of all women experience a urinary tract infection in their lifetime. ST131 are resistant to most antibiotics commonly used to treat urinary tract infections so it is important to be able to identify this type of E. coli early and treat the infection with an antibiotic that will work. Carbapenems are one of the few remaining types of antibiotics that are effective in treating ST131 but resistance to this antibiotic is increasing.

What should we be worried about?

Carbapenem resistance is an emerging problem, as the gene responsible is able to be easily transferred between bacteria. In the last couple of years carbapenem resistance genes have been reported in a small number of ST131 bacteria. The concern is that this gene will spread throughout the ST131 population, which is already the most successful *E. coli* clone to date. Not only would this limit treatment options for ST131 even further, it would also increase the chances that these resistance genes would be passed to other types of pathogenic bacteria.

How does our study help?

Our study provides a framework for understanding how these bacteria have evolved and spread around the globe. The genetic data that we produced can be used to develop new screening methods to ensure that ST131 are identified early in patients so that the best antibiotic treatment can be used. Ongoing surveillance of ST131 will also be important for tracking increased antibiotic resistance in this type of E. coli. In the longer term this work gives us the opportunity to develop new vaccines or therapies for preventing ST131. The fact that all ST131 are descended from a single ancestor means they may share an
Achilles’ heel that we can target.

How did we do the study?

We collected ST131 isolates from around the world from the year 2000 to 2011. We used “next generation” DNA sequencing to determine the genome of each isolate – the genome is the collection of all genes in an organism. Each E. coli has about 5000 genes, so we studied about half a million genes using bioinformatics, a discipline that merges biology and computing. The software that we developed to do this analysis and the data that we produced are now freely available to the rest of the scientific community.

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