Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens

Abstract

Whole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial-resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity.

Fig. 1

The time line of the ST22 MRSA pandemic. Bayesian phylogenetic tree reconstructing the ST22 MRSA pandemic over a 30-year period (8). Maximum clade credibility tree of ST22 MRSA based on BEAST analysis using a variable clock rate (uncorrelated lognormal) model. Tips of the tree are constrained by isolation dates; the time scale is shown at the base of the tree. Gains and losses (D) of genetic determinants for resistance to methicillin (SCCmec), fluoroquinolones (point mutations in grlA and gyrA), erythromycin (plasmid-encoded ermC), and clindamycin (mutations in ermC leader peptide region, c-ermC) have been mapped on the tree by applying the parsimony criterion. The figure depicts two pivotal events: the acquisition of methicillin resistance around 1977 and fluoroquinolone resistance in 1982 (red arrows). This clone then underwent rapid international spread, including countryspecific clonal expansions; countries highlighted in color.

Fig. 2

Origin and blast radius for the clonal expansion for three multidrug-resistant Gram-negative bacteria clones. The map summarizes data for the global dissemination of: dysentery causing Shigella sonnei clone lineage III-global, with a chromosomal insertion of a mobile genetic element encoding resistance to streptomycin, trimethoprim-sulfamethoxazole, and tetracycline (red); the typhoid fever pathogen Salmonella Typhi, clone H58, with a plasmid encoding resistance to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, streptomycin, and tetracycline (blue); health care–associated Klebsiella pneumoniae clone ST258, carrying the KPC carbapenemase encoding resistance to all β-lactam antimicrobials, including carbapenems and third-generation cephalosporins (gray).

Fig. 3

The epidemic of monophasic Salmonella Typhimurium (1,4,[5],12:i:-). The graph shows the number of Salmonella isolates from human infections at the French National Reference Centre for Salmonella during 2000 to 2016. The blue bars depict the total number of Salmonella spp. isolated by year over the defined period; the red plot depicts the number of Salmonella Typhimurium (1,4,[5],12:i:-) isolated by year.