Research ArticleGENETICS

Horizontal gene transfer rate is not the primary determinant of observed antibiotic resistance frequencies in Streptococcus pneumoniae

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Science Advances  20 May 2020:
Vol. 6, no. 21, eaaz6137
DOI: 10.1126/sciadv.aaz6137
  • Fig. 1 Schematic of the two possible explanations for variation in levels of antibiotic resistance between bacterial lineages.

    The first hypothesis (“everything is everywhere”; left) is that lineages with a long duration of carriage have high resistance frequencies because resistance is more beneficial to these lineages (because longer duration of carriage translates into a greater probability of antibiotic exposure per carriage episode). The second hypothesis (“genetics as limiting factor”; right) is that lineages with high HGT rate have high resistance frequencies because they acquire resistance determinants at a higher rate. Positive associations have been observed between all three variables (resistance, HGT rate, and duration of carriage). If the first hypothesis is correct, the association between resistance and HGT rate could be confounded by the causal path through the duration of carriage; if the second hypothesis is correct, the association between resistance and duration of carriage could be confounded by the causal path through HGT rate. In the case of a confounding effect, these associations will not be robust to adjusting for the confounded variable.

  • Fig. 2 Association with resistance multiplicity.

    Kendall rank correlation (τ) between SC resistance multiplicity and duration of carriage (unadjusted and adjusted for HR or GM); SC resistance multiplicity and HR (unadjusted and adjusted for duration of carriage); and SC resistance multiplicity and GM (unadjusted and adjusted for duration of carriage).Error bars represent 95% CIs and were computed by bootstrapping (see the Supplementary Materials). SCs with fewer than five episodes of carriage were excluded, giving a sample size of 43 SCs.

  • Fig. 3 Association with individual resistances.

    Kendall rank correlation (τ) between SC resistance to each antibiotic and duration of carriage (unadjusted and adjusted for HR or GM); SC resistance to each antibiotic and HR (unadjusted and adjusted for duration of carriage); and SC resistance to each antibiotic and GM (unadjusted and adjusted for duration of carriage). Opaque error bars represent 95% CIs, while transparent error bars represent 99% CIs; both were computed by bootstrapping (see the Supplementary Materials). SCs with fewer than five episodes of carriage were excluded, giving a sample size of 42 SCs.

  • Table 1 Akaike information criterion for regression models using serotype, SC, and serotype-SC combination as a predictor of resistance, HGT rate, and duration of carriage.

    The lowest AIC is indicated in bold.

    TraitSerotypeSCSerotype-SC
    Resistance
    multiplicity
    322431633191
    Carriage
    duration
    13,24313,22013,269
    HR437042714251
    GM88,92888,96088,965

Supplementary Materials

  • Supplementary Materials

    Horizontal gene transfer rate is not the primary determinant of observed antibiotic resistance frequencies in Streptococcus pneumoniae

    Sonja Lehtinen, Claire Chewapreecha, John Lees, William P. Hanage, Marc Lipsitch, Nicholas J. Croucher, Stephen D. Bentley, Paul Turner, Christophe Fraser, Rafał J. Mostowy

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