The fall and rise of group B Streptococcus in dairy cattle: reintroduction due to human-to-cattle host jumps?

Abstract

Group B Streptococcus (GBS; Streptococcus agalactiae ) is a major neonatal and opportunistic bacterial pathogen of humans and an important cause of mastitis in dairy cattle with significant impacts on food security. Following the introduction of mastitis control programmes in the 1950s, GBS was nearly eradicated from the dairy industry in northern Europe, followed by re-emergence in the 21st century. Here, we sought to explain this re-emergence based on short and long read sequencing of historical (1953–1978; n=44) and contemporary (1997–2012; n=76) bovine GBS isolates. Our data show that a globally distributed bovine-associated lineage of GBS was commonly detected among historical isolates but never among contemporary isolates. By contrast, tetracycline resistance, which is present in all major GBS clones adapted to humans, was commonly and uniquely detected in contemporary bovine isolates. These observations provide evidence for strain replacement and suggest a human origin of newly emerged strains. Three novel GBS plasmids were identified, including two showing >98 % sequence similarity with plasmids from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis , which co-exist with GBS in the human oropharynx. Our findings support introduction of GBS into the dairy population due to human-to-cattle jumps on multiple occasions and demonstrate that reverse zoonotic transmission can erase successes of animal disease control campaigns.

Keywords: Streptococcus agalactiae; anthroponosis; emergence; host adaptation; plasmid; reverse zoonosis.

Fig. 1.

Control and re-emergence of group B Streptococcus (GBS) is associated with strain replacement. (a) Frequency distribution of 120 GBS isolates from bovine milk, collected from 1953 to 1977 (n=44) and 1997 to 2012 (n=76), shows presence of six clonal complexes (CC; colour as indicated in panel b). Bovine-specific GBS lineage CC61 (purple) was last detected prior to 1970. Re-emergence of GBS in the Swedish dairy cattle population after a period of near-elimination is associated with CC1 (blue) and CC103/314 (yellow), which were first detected in 2004. Lineages CC23 (green) and CC6/10 (orange), which are also commonly found in other host species, were detected among historical and contemporary isolates. (b) Tetracycline resistance, a marker of adaptation of GBS to humans, was detected exclusively among contemporary bovine GBS isolates. The core genome phylogeny of historical and contemporary isolates (black and coloured leaves, respectively) is shown, with CC and presence of tet(M) and integrative conjugative elements (ICE), namely Tn916, Tn5801 and Tn5801-like. tet(M) was carried by Tn5801 in all ST314 isolates, and mostly by Tn916 among CC1 isolates. One ST28 isolate from 1978 did not belong to any of the major clades and is not shown. Tree was rooted at midpoint.

Fig. 2.

Hybrid Illumina-MinION assemblies of bovine group B Streptococcus (GBS) revealed the presence of plasmids and integrative mobilizable elements (IME). (a) Plasmid pZ2-265 has 99.28 % sequence similarity to plasmid pA996 (KC895877.1) from Streptococcus pyogenes or group A Streptococcus , GAS. (b) Plasmid pZ2-174 shows 98.85 % sequence similarity to pW2580 (AY907345.1) from Streptococcus dysgalactiae subsp. equisimilis or group G Streptococcus , GGS. (c) pZ2-336 did not show significant similarity with known plasmids, whilst a second circular element in the same genome assembly (d) could either belong to a novel unclassified mobile genetic element family or be an IME.

Fig. 3.

Phylogeny of the Lac.2 integrase amino acid sequences from bovine group B Streptococcus (GBS), with their insertion site (coloured strip) and Lac.2 variant (symbols), illustrating the plasticity of the accessory genome. Insertion sites have been mapped on an example GBS genome. Gene yxdL was found in multiple copies within the same genome, with Lac.2 detected next to the copy present in the region around 1.25 Mbp. When Lac.2 was found at the edge of a contig, it was not possible to determine the site of integration (n=13, blank colour strip) and the integrase sequence (n=10, not present in tree).

Fig. 4.

Schematic representation of the relationship between the biological and ecological species concept for streptococci. The bacterial core genome defines biological species (rows) whereas the bacterial accessory genome drives and is driven by the ecological niche inhabited by the bacteria, in this case the host species (columns), creating ‘ecological species’. Acquisition of host-associated mobile genetic elements through lateral transfer between pyogenic streptococcal species in one host, as described for phages, transposons, and transporters in humans [7], and for lactose and nisin operons in cattle [26], followed by transmission between host species, may explain the detection of human-associated accessory genome content in bovine group B Streptococcus as observed in this study for tetracycline resistance and plasmids.