Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA.

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Waves of resistance: Staphylococcus aureus in the antibiotic era

The emergence of global history has been one of the more notable features of academic history over the past three decades. Although historians of disease were among the pioneers of one of its earlier incarnations—world history—the recent “global turn” has made relatively little impact on histories of health, disease, and medicine. Most continue to be framed by familiar entities such as the colony or nation-state or are confined to particular medical “traditions.” This article aims to show what can be gained from taking a broader perspective. Its purpose is not to replace other ways of seeing or to write a new “grand narrative” but to show how transnational and transimperial approaches are vital to understanding some of the key issues with which historians of health, disease, and medicine are concerned. Moving on from an analysis of earlier periods of integration, the article offers some reflections on our own era of globalization and on the emerging field of global health.

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A Global Perspective: Reframing the History of Health, Medicine, and Disease.

Advances in high-throughput sequencing and ‘omics technologies are revolutionizing studies of naturally occurring microbial communities. Comprehensive investigations of microbial lifestyles require the ability to interactively organize and visualize genetic information and to incorporate subtle differences that enable greater resolution of complex data. Here we introduce anvi’o, an advanced analysis and visualization platform that offers automated and human-guided characterization of microbial genomes in metagenomic assemblies, with interactive interfaces that can link ‘omics data from multiple sources into a single, intuitive display. Its extensible visualization approach distills multiple dimensions of information about each contig, offering a dynamic and unified work environment for data exploration, manipulation, and reporting. Using anvi’o, we re-analyzed publicly available datasets and explored temporal genomic changes within naturally occurring microbial populations through de novo characterization of single nucleotide variations, and linked cultivar and single-cell genomes with metagenomic and metatranscriptomic data. Anvi’o is an open-source platform that empowers researchers without extensive bioinformatics skills to perform and communicate in-depth analyses on large ‘omics datasets.

Anvi'o: an advanced analysis and visualization platform for 'omics data.

SUMMARY Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), which have become the most problematic hospital pathogens.

https://cmr.asm.org/content/cmr/31/4/e00088-17.full-text.pdf

Mobile Genetic Elements Associated with Antimicrobial Resistance

Current methods for differentiating isolates of predominant lineages of pathogenic bacteria often do not provide sufficient resolution to define precise relationships. Here, we describe a high-throughput genomics approach that provides a high-resolution view of the epidemiology and microevolution of a dominant strain of methicillin-resistant Staphylococcus aureus (MRSA). This approach reveals the global geographic structure within the lineage, its intercontinental transmission through four decades, and the potential to trace person-to-person transmission within a hospital environment. The ability to interrogate and resolve bacterial populations is applicable to a range of infectious diseases, as well as microbial ecology.

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Evolution of MRSA During Hospital Transmission and Intercontinental Spread

Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.

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Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

A small number of clonal lineages dominates the global population structure of methicillin-resistant Staphylococcus aureus (MRSA), resulting in the concept that MRSA has emerged on a few occasions after penicillinase-stable β-lactam antibiotics were introduced to clinical practice, followed by intercontinental spread of individual clones. We investigated the evolutionary history of an MRSA clone (ST5) by mutation discovery at 108 loci (46 kb) within a global collection of 135 isolates. The SNPs that were ascertained define a radial phylogenetic structure within ST5 consisting of at least 5 chains of mutational steps that define geographically associated clades. These clades are not concordant with previously described groupings based on staphylococcal protein A gene (spa) typing. By mapping the number of independent imports of the staphylococcal cassette chromosome methicillin-resistance island, we also show that import has occurred on at least 23 occasions within this single sequence type and that the progeny of such recombinant strains usually are distributed locally rather than globally. These results provide strong evidence that geographical spread of MRSA over long distances and across cultural borders is a rare event compared with the frequency with which the staphylococcal cassette chromosome island has been imported.

https://www.pnas.org/content/pnas/105/37/14130.full.pdf

Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus

The continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK. 

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Mirjam Feldkamp

Papers

Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus

Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC