CRISPR-Cas is associated with fewer antibiotic resistance genes in bacterial pathogens

Abstract

The acquisition of antibiotic resistance (ABR) genes via horizontal gene transfer (HGT) is a key driver of the rise in multidrug resistance amongst bacterial pathogens. Bacterial defence systems per definition restrict the influx of foreign genetic material, and may therefore limit the acquisition of ABR. CRISPR-Cas adaptive immune systems are one of the most prevalent defences in bacteria, found in roughly half of bacterial genomes, but it has remained unclear if and how much they contribute to restricting the spread of ABR. We analysed approximately 40 000 whole genomes comprising the full RefSeq dataset for 11 species of clinically important genera of human pathogens, including Enterococcus, Staphylococcus, Acinetobacter and Pseudomonas. We modelled the association between CRISPR-Cas and indicators of HGT, and found that pathogens with a CRISPR-Cas system were less likely to carry ABR genes than those lacking this defence system. Analysis of the mobile genetic elements (MGEs) targeted by CRISPR-Cas supports a model where this host defence system blocks important vectors of ABR. These results suggest a potential 'immunocompromised' state for multidrug-resistant strains that may be exploited in tailored interventions that rely on MGEs, such as phages or phagemids, to treat infections caused by bacterial pathogens. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.

Keywords: CRISPR-Cas; antibiotic resistance; horizontal gene transfer; integrative conjugative elements; mobile genetic elements; plasmids.

Figure 1.

Predicted probability of CRISPR-Cas presence (y-axis) from binomial GLMs for (a) ABR gene count and numbers of the potential ABR vectors, (b) ICEs, (c) intI1 (integrons) and (d) plasmid replicons. Predictions are presented for elements that are found in each species. Shaded areas show 95% confidence intervals.

Figure 2.

Prediction plots from Bayesian Poisson GLMs of ABR gene counts for (a) CRISPR-Cas type and (b) number of spacers. Each column represents an individual species. Shaded areas show 95% credible intervals. (Online version in colour.)

Figure 3.

Prediction plot overlaying two Bayesian Poisson GLMs of ABR gene counts according to counts of spacers (with known targets) targeting MGEs with and without ABR, faceted by species. Shaded areas show 95% credible intervals. (Online version in colour.)