Bacterial transmission tactics

Abstract

the extent that a single clone might be expected to evolve within an infected individual , and was used to define a baseline metric for the expected rate of sequence change, when comparing strains from different people. The authors conclude that, if in the analysed regions there are fewer than 20 single DNA-base differences-known as single nucleotide polymorphisms-between strains from different individuals, this suggests a probable human-transmission event, rather than independent environmental acquisition of the strains. However, epidemiological evidence of cross-patient exposures was not available to corroborate this. Bryant and colleagues conducted infection tests using cellular assays and mouse models to determine whether the dominant circulating clones are more virulent than other M. abscessus strains. Compared with the non-clustered bacterial strains tested, the dominant clones exhibited greater uptake into cells and increased intracellular survival, and yielded higher numbers of bacteria in mice, suggesting that they have adapted to become more robust and successful pathogens. The dominant clones also had more mutations associated with drug resistance and correlated with poorer clinical outcomes. Whether the dominant clones are better at being transmitted than are non-clustered strains was not directly tested. Although Bryant and colleagues' impressive feat of genomic analysis illuminates the global population structure of a potentially deadly pathogen, further investigation is needed. The genomic diversity of environmental M. abscessus is unknown, and this raises the question of whether environmental bacterial clades might show some genetic overlap with the observed dominant clinical clades. If the geno types of the dominant transmissible clones are also dominant in the environment, how might this affect the inference of widespread human transmission? To definitively define the occurrence, frequency and existence of a human-to-human transmission mechanism , epidemiological studies must also be conducted, together with genomic pathogen surveillance, as Bryant and colleagues did in a previous study focused on a local M. abscessus outbreak 11. Hypotheses that challenge paradigms are essential for scientific progress, but they also warrant careful follow-up and should be accompanied by rigorous testing of the previously held dogma. Bryant and co-workers' application of high-throughput genomic sequencing of pathogens underscores the importance of continuing to push the boundaries of such technology in biological and medical fields. This approach offers researchers a tool with which to potentially capture snapshots of evolution, identify previously unobserved pathogen characteristics , and monitor pathogens in a state of transition as their infection capabilities or modes of transmission evolve. When Charles Darwin and Alfred Russel Wallace developed the theory of evolution by natural selection, they could only have imagined how scientists' ability to investigate evolution would improve over time to reach the fine-scale analysis that is now possible. ■ M. abscessus subspecies, termed M. a. abscessus, M. a. massiliense and M. a. bolletii. Bryant and colleagues found three large and seemingly clonal clusters of bacterial samples that have near-identical sequences in the analysed genomic regions. Two of these clusters were in M. a. abscessus and one was in M. a. massiliense. Because the strains within each cluster were so similar at the genomic level, the authors inferred that, rather than representing the environmental acquisition of bacteria presumed to be genetically diverse, these strains might represent widespread human transmission of three bacterial clones, which they termed dominant circulating clones (Fig. 1). The authors propose that the local transmission of such clones could be mediated through asymptomatic human carriers, long-lived infectious cough aerosols or an inanimate intermediate, such as an infected surface. Cystic-fibrosis clinics follow strict infection-control guidelines developed specifically to reduce the potential for patient-to-patient transmission of other types of bacterium that infect the airways in cystic fibrosis. The dominant clones were observed on different continents, and a mechanism for such long-distance transmission has not been identified. To test whether a strain is truly clonal, the authors compared whole-genome-sequence information over time for strains derived from the same patients. This revealed Environmental transmission Lung infection Water DNA Mycobacterium abscessus Soil Human-to-human transmission Cough aerosol? Surface contamination? Intercontinental spread? Figure 1 | Possible change in the transmission mode of a bacterial infection. The bacterial species Mycobacterium abscessus exists in environmental niches such as soil and water 6. It is assumed that bacteria growing in such niches in the wild probably have diverse DNA sequences (indicated by different colours) containing many variations in individual DNA bases known as single nucleotide polymorphisms. M. abscessus from environmental sources can cause lung infections in humans 6. To investigate an increase in M. abscessus infections observed in many locations 8,9 , Bryant et al. 4 conducted DNA sequencing of 1,080 clinical strains of M. abscessus from around the world. They report that some of the strains were almost identical at the genetic level. Such close genetic similarity might mean that these strains are bacterial clones that have arisen from a human mode of infection transmission. The authors speculate that human-to-human transmission could occur by infection mechanisms such as cough aerosols or surface contamination. How the transmission of such clones might occur across continents is unknown. 4 9 6 | N A T U R E | V O L 5 4 3 | 2 3 M A R C H 2 0 1 7 NEWS & VIEWS RESEARCH © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e. A l l r i g h t s r e s e r v e d .