Linking phenotype, genotype and ecology: antimicrobial resistance in the zoonotic pathogen Streptococcus suis

• Published in: bioRxiv
• Main Authors: Hadjirin, Nazreen F, Miller, Eric L, Murray, Gemma G R, Yen, Phung L K, Phuc, Ho D, Wileman, Thomas M, Hernandez-Garcia, Juan, Williamson, Susanna M, Parkhill, Julian, Maskell, Duncan J, Zhou, Rui, Fittipaldi, Nahuel, Gottschalk, Marcelo, A (Dan) W Tucker, Ngo Thi Hoa, Welch, John J, Weinert, Lucy A
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 13.05.2020
• Subjects: Alleles; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Drug resistance; Epistasis; Genomes; Genotypes; Minimum inhibitory concentration; Multidrug resistance; Pathogens; Phenotypes; Pleiotropy; Streptococcus suis; Zoonoses
• DOI: 10.1101/2020.05.05.078493

Antimicrobial resistance (AMR) is a major problem for human and animal health, and can co-vary with features of the bacterial genome, its ecological context, and with other traits. Here, we present an integrated study of AMR in the porcine zoonotic pathogen, Streptococcus suis. Collecting a diverse panel of 678 isolates, we obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 widely used antimicrobials, from eight distinct classes. Then using whole genome sequences for each isolate, we identified 42 candidate AMR alleles, of which 21 were novel for S. suis. The presence of these alleles explains most of the observed variation in MIC but there was also unexplained variation, partly due to alleles of small effect, and epistatic interactions. We find that MIC varies with S. suis genetic background and country, but less so with clinical phenotype, serotype or over time. These ecological patterns are largely explained by allele prevalence. MIC values for different antibiotic classes positively correlate with one another, but there is limited evidence of direct pleiotropy, where single alleles confer resistance to multiple drug classes. Instead, this covariation is due to alleles for separate classes appearing together, but not necessarily in the same genomic region. The result is a significant excess of multi-drug resistant isolates. Indeed, we found more isolates that carried resistance alleles to five classes of antibiotics than isolates than carried no resistance alleles. We discuss the implications of our results for combatting AMR in S. suis, and for understanding multi-drug resistance in bacteria. Competing Interest Statement The authors have declared no competing interest. Footnotes * Section on Data availability updated with an additional lAccession number. "The gene vgaF from isolate 1230091 has accession MT431628".